Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   43857   clinical trials with a EudraCT protocol, of which   7284   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Download PDF

    Clinical Trial Results:
    A Multicenter Single-arm Extension Study to Describe the Long-term Safety of AMG 416 in the Treatment of Secondary Hyperparathyroidism in Subjects With Chronic Kidney Disease on Hemodialysis

    Summary
    EudraCT number
    		 2013-004136-30
    Trial protocol
    		 SE   IT   BE   AT   ES   PT   LT   PL   CZ   DK   LV   DE   GR   HU   NL  
    Global end of trial date
    26 Jun 2017

    Results information
    Results version number
    		 v1(current)
    This version publication date
    06 Jul 2018
    First version publication date
    06 Jul 2018
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    20130213
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02102204
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Amgen Inc.
    Sponsor organisation address
    One Amgen Center Drive, Thousand Oaks, CA, United States, 91320
    Public contact
    IHQ Medical Info-Clinical Trials, Amgen (EUROPE) GmbH, MedInfoInternational@amgen.com
    Scientific contact
    IHQ Medical Info-Clinical Trials, Amgen (EUROPE) GmbH, MedInfoInternational@amgen.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    26 Jun 2017
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    26 Jun 2017
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objective of the study was to characterize the long-term safety and tolerability of etelcalcetide in the treatment of secondary hyperparathyroidism in subjects with chronic kidney disease (CKD) receiving hemodialysis.
    Protection of trial subjects
    This study was conducted in accordance with International Conference on Harmonisation (ICH), Good Clinical Practice (GCP), and country-specific regulations/guidelines. The study protocol and all amendments, the proposed informed consent form, other written subject information, and any proposed advertising materials were reviewed by the applicable independent ethics committee (IEC) or institutional review board (IRB) at each study center. The applicable IEC/IRB provided written approval, and a copy of the approval was received by Amgen before recruitment of subjects into the study and shipment of etelcalcetide. Before a subject’s participation in the clinical study, the investigator at each study center obtained written informed consent from the subject after adequate explanation of the aims, methods, anticipated benefits, and potential hazards of the study, and before any protocol-specific screening procedures or etelcalcetide was administered.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    25 Mar 2014
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Australia: 11
    Country: Number of subjects enrolled
    Austria: 11
    Country: Number of subjects enrolled
    Belgium: 33
    Country: Number of subjects enrolled
    Czech Republic: 34
    Country: Number of subjects enrolled
    Denmark: 4
    Country: Number of subjects enrolled
    France: 20
    Country: Number of subjects enrolled
    Germany: 25
    Country: Number of subjects enrolled
    Greece: 17
    Country: Number of subjects enrolled
    Hungary: 71
    Country: Number of subjects enrolled
    Israel: 10
    Country: Number of subjects enrolled
    Italy: 35
    Country: Number of subjects enrolled
    Lithuania: 10
    Country: Number of subjects enrolled
    Netherlands: 2
    Country: Number of subjects enrolled
    New Zealand: 4
    Country: Number of subjects enrolled
    Poland: 33
    Country: Number of subjects enrolled
    Portugal: 29
    Country: Number of subjects enrolled
    Russian Federation: 117
    Country: Number of subjects enrolled
    Spain: 56
    Country: Number of subjects enrolled
    Sweden: 6
    Country: Number of subjects enrolled
    Switzerland: 10
    Country: Number of subjects enrolled
    Turkey: 11
    Country: Number of subjects enrolled
    Canada: 27
    Country: Number of subjects enrolled
    United States: 326
    Worldwide total number of subjects
    902
    EEA total number of subjects
    386
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    589
    From 65 to 84 years
    294
    85 years and over
    19

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 The study was conducted at 229 study centers in Europe, Australia, New Zealand, and North America.

    Pre-assignment
    Screening details
    		 A total of 902 participants were enrolled in Study 20130213: 215 and 200 participants from the cinacalcet and etelcalcetide groups of the double-blind parent Study 20120360 (2013-000192-33), respectively, and 487 participants from the open-label parent Studies 20120231 (2012-002808-41) and 20120334 (NCT01576146).

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Not applicable
    Blinding used
    		 Not blinded

    Arms
    Arm title
    		 Etelcalcetide
    Arm description
    		 Participants received etelcalcetide three times a week (TIW) by bolus injection at the end of hemodialysis. The minimum etelcalcetide dose in this study was 2.5 mg and the maximum dose was 15 mg. Etelcalcetide dose was titrated to maintain parathyroid hormone levels within 2x to 9x the upper limit of normal based on the reference range of the assay used at the individual study center.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Etelcalcetide
    Investigational medicinal product code
    AMG 416
    Other name
    KAI-4169 Parsabiv
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous bolus use
    Dosage and administration details
    Etelcalcetide was administered TIW by bolus injection into the venous line of the dialysis circuit at the end of hemodialysis.

    Number of subjects in period 1
    		Etelcalcetide
    Started
    902
    Received Etelcalcetide
    884
    Completed
    603
    Not completed
    299
         Consent withdrawn by subject
    137
         Death
    92
         Lost to follow-up
    65
         Sponsor decision
    5

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Overall Study
    Reporting group description
    		 Participants were enrolled to receive etelcalcetide three times a week (TIW) by bolus injection at the end of hemodialysis. The minimum etelcalcetide dose in this study was 2.5 mg and the maximum dose was 15 mg. Etelcalcetide dose was titrated to maintain parathyroid hormone levels within 2x to 9x the upper limit of normal based on the reference range of the assay used at the individual study center.

    Reporting group values
    		 Overall Study Total
    Number of subjects
    		 902 902
    Age Categorical
    Units: Subjects
        Adults (18-64 years)
    		 589 589
        From 65-84 years
    		 294 294
        85 years and over
    		 19 19
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    		 57.8 ± 14.3 -
    Gender Categorical
    Units: Subjects
        Female
    		 365 365
        Male
    		 537 537
    Race
    Units: Subjects
        American Indian or Alaska Native
    		 1 1
        Asian
    		 16 16
        Black (or African American)
    		 195 195
        Native Hawaiian or Other Pacific Islander
    		 9 9
        White
    		 670 670
        Other
    		 11 11
    Ethnicity
    Units: Subjects
        Hispanic/Latino
    		 79 79
        Not Hispanic/Latino
    		 823 823
    Baseline Parathyroid Hormone Level
    Data are reported for 871 participants with available data.
    Units: pg/mL
        arithmetic mean (standard deviation)
    		 522.1 ± 563.9 -

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Etelcalcetide
    Reporting group description
    		 Participants received etelcalcetide three times a week (TIW) by bolus injection at the end of hemodialysis. The minimum etelcalcetide dose in this study was 2.5 mg and the maximum dose was 15 mg. Etelcalcetide dose was titrated to maintain parathyroid hormone levels within 2x to 9x the upper limit of normal based on the reference range of the assay used at the individual study center.

    Primary: Number of Participants With Adverse Events

    		 Close Top of page
    End point title
    		 Number of Participants With Adverse Events [1]
    End point description
    A serious adverse event is an AE that met at least 1 of the following criteria: • fatal • life threatening • required in-patient hospitalization or prolongation of existing hospitalization • resulted in persistent or significant disability/incapacity • congenital anomaly/birth defect • other medically important serious event. The relationship of each AE to study treatment was assessed by the investigator. The following AE grading scale was used: Mild: Transient or mild discomfort; no limitation in activity; no medical intervention/therapy required Moderate: Mild to moderate limitation in activity-some assistance may be needed; no or minimal medical intervention/therapy required Severe: Marked limitation in activity, some assistance usually required; medical intervention/therapy required, hospitalization possible Life-threatening: Extreme limitation in activity, significant assistance required, significant medical intervention/therapy required, hospitalization probable.
    End point type
    Primary
    End point timeframe
    From the date of first dose of etelcalcetide (in the current study) and up to 30 days after the last dose as of the final analysis data cut-off date of 26 June 2017; median duration of treatment was 563 days.
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: The study was descriptive; no formal hypothesis was tested.
    End point values
    		 Etelcalcetide
    Number of subjects analysed
    884
    Units: participants
        Any adverse event
    768
        Serious adverse events
    436
        Treatment-related adverse events
    288
        Serious treatment-related adverse events
    4
        AEs leading to discontinuation of etelcalcetide
    41
        Fatal adverse events
    89
        Mild adverse events
    122
        Moderate adverse events
    219
        Severe adverse events
    325
        Life-threatening adverse events
    102
    No statistical analyses for this end point

    Secondary: Percentage of Participants With Parathyroid Hormone Levels Between Two to Nine-times the Upper Limit of Normal

    		 Close Top of page
    End point title
    		 Percentage of Participants With Parathyroid Hormone Levels Between Two to Nine-times the Upper Limit of Normal
    End point description
    The percentage of participants who maintained plasma parathyroid hormone (PTH) levels within the Kidney Disease Improving Global Outcomes (KDIGO) recommended range of not less than 2x the upper limit of normal (ULN) and not greater than 9x the ULN at months 6, 12, and 18, with the ULN based on the reference range of the assay used at the individual clinical site.
    End point type
    Secondary
    End point timeframe
    Months 6, 12, and 18
    End point values
    		 Etelcalcetide
    Number of subjects analysed
    884 [2]
    Units: percentage of participants
    number (confidence interval 95%)
        Month 6 (N = 770)
    67.0 (63.6 to 70.3)
        Month 12 (N = 679)
    73.2 (69.7 to 76.5)
        Month 18 (N = 540)
    71.9 (67.9 to 75.6)
    Notes
    [2] - Participants who received at least 1 dose of etelcalcetide with available data at each time point.
    No statistical analyses for this end point

    Secondary: Percentage of Participants With Serum Phosphorus ≤ the ULN

    		 Close Top of page
    End point title
    		 Percentage of Participants With Serum Phosphorus ≤ the ULN
    End point description
    Percentage of participants with serum phosphorus less than or equal to the upper limit of normal for the assay used.
    End point type
    Secondary
    End point timeframe
    Months 6, 12, and 18
    End point values
    		 Etelcalcetide
    Number of subjects analysed
    884
    Units: percentage of participants
    number (confidence interval 95%)
        Month 6 (N = 774)
    39.4 (35.9 to 43.0)
        Month 12 (N = 625)
    40.0 (36.1 to 44.0)
        Month 18 (N = 478)
    36.8 (32.5 to 41.3)
    No statistical analyses for this end point

    Secondary: Percentage of Participants With Serum Corrected Calcium < 7.5 mg/dL

    		 Close Top of page
    End point title
    		 Percentage of Participants With Serum Corrected Calcium < 7.5 mg/dL
    End point description
    The percentage of participants with serum corrected calcium (cCa) reported for cumulative time intervals from day 1 through months 6, 12, and 18, using the participant's lowest recorded corrected calcium value during the time interval. If serum albumin was less than 4.0 g/dL, serum calcium was corrected according to the following formula: cCa (mg/dL) = total calcium (mg/dL) + (4 – albumin [g/dL])*0.8. If serum albumin was > 4.0 g/dL no correction was made.
    End point type
    Secondary
    End point timeframe
    From day 1 to months 6, 12, and 18
    End point values
    		 Etelcalcetide
    Number of subjects analysed
    871 [3]
    Units: percentage of participants
    number (confidence interval 95%)
        Day 1 to Month 6
    9.5 (7.7 to 11.7)
        Day 1 to Month 12
    14.1 (11.9 to 16.6)
        Day 1 to Month 18
    16.3 (13.9 to 18.9)
    Notes
    [3] - Participants who received at least 1 dose of etelcalcetide with available day 1 data
    No statistical analyses for this end point

    Secondary: Number of Participants With Shifts From Baseline Grade 0 or 1 to Postbaseline Grade 3 or 4 for Laboratory Parameters

    		 Close Top of page
    End point title
    		 Number of Participants With Shifts From Baseline Grade 0 or 1 to Postbaseline Grade 3 or 4 for Laboratory Parameters
    End point description
    The Common Terminology Criteria for Adverse Events (CTCAE) grades for laboratory parameter values were defined based on the upper/lower limit of normal from the local laboratories contracted by the study centers
    End point type
    Secondary
    End point timeframe
    Baseline to end of treatment; median duration of treatment was 563 days.
    End point values
    		 Etelcalcetide
    Number of subjects analysed
    884 [4]
    Units: participants
        Increased Alanine Aminotransferase Grade 1 to 3
    1
        Increased Alkaline Phosphatase Grade 1 to 3
    2
        Increased Aspartate Aminotransferase Grade 1 to 3
    1
        Decreased Corrected Calcium Grade 1 to 3
    18
        Decreased Corrected Calcium Grade 1 to 4
    2
        Decreased ionized Calcium Grade 1 to 3
    1
        Decreased ionized Calcium Grade 1 to 4
    2
        Decreased Phosphorous Grade 1 to 3
    1
    Notes
    [4] - Participants who received at least 1 dose of etelcalcetide
    No statistical analyses for this end point

    Secondary: Number of Participants Who Developed Positive Binding Anti-Etelcalcetide Antibodies

    		 Close Top of page
    End point title
    		 Number of Participants Who Developed Positive Binding Anti-Etelcalcetide Antibodies
    End point description
    The number of participants who were binding antibody positive post-baseline with a negative or no result at baseline (where baseline for participants previously treated with etelcalcetide is Day 1 of the first study in which they were exposed to etelcalcetide and for participants previously treated with cinacalcet is the ending time point for study 20120360).
    End point type
    Secondary
    End point timeframe
    Baseline and every 6 months (up to 24 months)
    End point values
    		 Etelcalcetide
    Number of subjects analysed
    808 [5]
    Units: participants
    111
    Notes
    [5] - Participants who received at least 1 dose of etelcalcetide and a post-baseline antibody result
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    From the date of first dose of etelcalcetide (in the current study) and up to 30 days after the last dose as of the final analysis data cut-off date of 26 June 2017; median duration of treatment was 563 days.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    20.0
    Reporting groups
    Reporting group title
    Etelcalcetide
    Reporting group description
    		 Participants received etelcalcetide three times a week (TIW) by bolus injection at the end of hemodialysis. The minimum etelcalcetide dose in this study was 2.5 mg and the maximum dose was 15 mg. Etelcalcetide dose was titrated to maintain parathyroid hormone levels within 2x to 9x the upper limit of normal based on the reference range of the assay used at the individual study center.

    Serious adverse events
    		 Etelcalcetide
    Total subjects affected by serious adverse events
         subjects affected / exposed
    436 / 884 (49.32%)
         number of deaths (all causes)
    89
         number of deaths resulting from adverse events
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Basal cell carcinoma
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Benign neoplasm
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Benign neoplasm of bladder
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Bladder cancer
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Bladder papilloma
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Breast cancer
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Carcinoid tumour of the small bowel
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Endometrial adenocarcinoma
         subjects affected / exposed
    2 / 884 (0.23%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Lung adenocarcinoma
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Malignant melanoma
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Prostate cancer
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Renal cell carcinoma
         subjects affected / exposed
    2 / 884 (0.23%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Vascular disorders
    Accelerated hypertension
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Aortic aneurysm
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Aortic dissection
         subjects affected / exposed
    2 / 884 (0.23%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 2
    Aortic stenosis
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Arterial occlusive disease
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Arteriosclerosis
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Arteriovenous fistula
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Axillary vein thrombosis
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Deep vein thrombosis
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Exsanguination
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Extremity necrosis
         subjects affected / exposed
    3 / 884 (0.34%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    Haematoma
         subjects affected / exposed
    4 / 884 (0.45%)
         occurrences causally related to treatment / all
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    Hypertension
         subjects affected / exposed
    9 / 884 (1.02%)
         occurrences causally related to treatment / all
    0 / 13
         deaths causally related to treatment / all
    0 / 0
    Hypertensive crisis
         subjects affected / exposed
    6 / 884 (0.68%)
         occurrences causally related to treatment / all
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    Hypertensive emergency
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Hypotension
         subjects affected / exposed
    8 / 884 (0.90%)
         occurrences causally related to treatment / all
    0 / 8
         deaths causally related to treatment / all
    0 / 0
    Hypovolaemic shock
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Iliac artery occlusion
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Malignant hypertension
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Orthostatic hypotension
         subjects affected / exposed
    3 / 884 (0.34%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    Peripheral arterial occlusive disease
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Peripheral artery aneurysm
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Peripheral artery occlusion
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Peripheral artery stenosis
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Peripheral artery thrombosis
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Peripheral ischaemia
         subjects affected / exposed
    7 / 884 (0.79%)
         occurrences causally related to treatment / all
    0 / 8
         deaths causally related to treatment / all
    0 / 0
    Peripheral vascular disorder
         subjects affected / exposed
    4 / 884 (0.45%)
         occurrences causally related to treatment / all
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    Shock haemorrhagic
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Steal syndrome
         subjects affected / exposed
    2 / 884 (0.23%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Superior vena cava stenosis
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Superior vena cava syndrome
         subjects affected / exposed
    2 / 884 (0.23%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Thrombophlebitis
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Vascular calcification
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Vascular compression
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Venous occlusion
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    5 / 884 (0.57%)
         occurrences causally related to treatment / all
    0 / 5
         deaths causally related to treatment / all
    0 / 1
    Chest pain
         subjects affected / exposed
    7 / 884 (0.79%)
         occurrences causally related to treatment / all
    0 / 8
         deaths causally related to treatment / all
    0 / 0
    Death
         subjects affected / exposed
    4 / 884 (0.45%)
         occurrences causally related to treatment / all
    1 / 4
         deaths causally related to treatment / all
    1 / 4
    Drowning
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Fatigue
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    General physical health deterioration
         subjects affected / exposed
    3 / 884 (0.34%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 2
    Hyperpyrexia
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Impaired healing
         subjects affected / exposed
    2 / 884 (0.23%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    Ischaemic ulcer
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Malaise
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Non-cardiac chest pain
         subjects affected / exposed
    11 / 884 (1.24%)
         occurrences causally related to treatment / all
    0 / 14
         deaths causally related to treatment / all
    0 / 0
    Oedema peripheral
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Pyrexia
         subjects affected / exposed
    11 / 884 (1.24%)
         occurrences causally related to treatment / all
    0 / 11
         deaths causally related to treatment / all
    0 / 0
    Sudden death
         subjects affected / exposed
    4 / 884 (0.45%)
         occurrences causally related to treatment / all
    0 / 4
         deaths causally related to treatment / all
    0 / 4
    Systemic inflammatory response syndrome
         subjects affected / exposed
    2 / 884 (0.23%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Immune system disorders
    Chronic allograft nephropathy
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Transplant rejection
         subjects affected / exposed
    2 / 884 (0.23%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Reproductive system and breast disorders
    Benign prostatic hyperplasia
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Postmenopausal haemorrhage
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Priapism
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Uterine polyp
         subjects affected / exposed
    2 / 884 (0.23%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Acute pulmonary oedema
         subjects affected / exposed
    3 / 884 (0.34%)
         occurrences causally related to treatment / all
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    Acute respiratory failure
         subjects affected / exposed
    3 / 884 (0.34%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 1
    Choking
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    4 / 884 (0.45%)
         occurrences causally related to treatment / all
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    Cystic lung disease
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Dependence on respirator
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Dyspnoea
         subjects affected / exposed
    12 / 884 (1.36%)
         occurrences causally related to treatment / all
    0 / 14
         deaths causally related to treatment / all
    0 / 0
    Epistaxis
         subjects affected / exposed
    3 / 884 (0.34%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    Haemothorax
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Hydrothorax
         subjects affected / exposed
    2 / 884 (0.23%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Hypoxia
         subjects affected / exposed
    6 / 884 (0.68%)
         occurrences causally related to treatment / all
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    Orthopnoea
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Pleural effusion
         subjects affected / exposed
    3 / 884 (0.34%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    Pneumonia aspiration
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Pulmonary oedema
         subjects affected / exposed
    12 / 884 (1.36%)
         occurrences causally related to treatment / all
    0 / 13
         deaths causally related to treatment / all
    0 / 0
    Respiratory arrest
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Respiratory failure
         subjects affected / exposed
    4 / 884 (0.45%)
         occurrences causally related to treatment / all
    0 / 5
         deaths causally related to treatment / all
    0 / 2
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Confusional state
         subjects affected / exposed
    2 / 884 (0.23%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Delirium
         subjects affected / exposed
    3 / 884 (0.34%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 1
    Depression
         subjects affected / exposed
    3 / 884 (0.34%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    Depression suicidal
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Insomnia
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Mental status changes
         subjects affected / exposed
    8 / 884 (0.90%)
         occurrences causally related to treatment / all
    0 / 8
         deaths causally related to treatment / all
    0 / 0
    Suicide attempt
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Product issues
    Device dislocation
         subjects affected / exposed
    2 / 884 (0.23%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Device failure
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Device malfunction
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Device occlusion
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Stent malfunction
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Thrombosis in device
         subjects affected / exposed
    6 / 884 (0.68%)
         occurrences causally related to treatment / all
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    Investigations
    Blood potassium decreased
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Paracentesis
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Peripheral pulse decreased
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Injury, poisoning and procedural complications
    Acetabulum fracture
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Ankle fracture
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Arteriovenous fistula aneurysm
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Arteriovenous fistula occlusion
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Arteriovenous fistula site complication
         subjects affected / exposed
    11 / 884 (1.24%)
         occurrences causally related to treatment / all
    0 / 11
         deaths causally related to treatment / all
    0 / 0
    Arteriovenous fistula site haematoma
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Arteriovenous fistula site haemorrhage
         subjects affected / exposed
    4 / 884 (0.45%)
         occurrences causally related to treatment / all
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    Arteriovenous fistula thrombosis
         subjects affected / exposed
    24 / 884 (2.71%)
         occurrences causally related to treatment / all
    0 / 27
         deaths causally related to treatment / all
    0 / 1
    Arteriovenous graft site haemorrhage
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Arteriovenous graft thrombosis
         subjects affected / exposed
    9 / 884 (1.02%)
         occurrences causally related to treatment / all
    0 / 14
         deaths causally related to treatment / all
    0 / 0
    Cervical vertebral fracture
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Contusion
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Craniocerebral injury
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Fall
         subjects affected / exposed
    7 / 884 (0.79%)
         occurrences causally related to treatment / all
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    Femur fracture
         subjects affected / exposed
    2 / 884 (0.23%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Hip fracture
         subjects affected / exposed
    2 / 884 (0.23%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    Joint dislocation
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Laceration
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Limb injury
         subjects affected / exposed
    4 / 884 (0.45%)
         occurrences causally related to treatment / all
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    Lower limb fracture
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Lumbar vertebral fracture
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Overdose
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Patella fracture
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Pelvic fracture
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Post procedural haemorrhage
         subjects affected / exposed
    2 / 884 (0.23%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Post-traumatic pain
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Procedural hypertension
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Procedural hypotension
         subjects affected / exposed
    3 / 884 (0.34%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    Procedural intestinal perforation
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Procedural pain
         subjects affected / exposed
    3 / 884 (0.34%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    Radius fracture
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Rib fracture
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Road traffic accident
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Shunt aneurysm
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Shunt occlusion
         subjects affected / exposed
    2 / 884 (0.23%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Shunt stenosis
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Spinal compression fracture
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Subarachnoid haemorrhage
         subjects affected / exposed
    4 / 884 (0.45%)
         occurrences causally related to treatment / all
    0 / 4
         deaths causally related to treatment / all
    0 / 1
    Subdural haematoma
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Tendon rupture
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Thermal burn
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Tibia fracture
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Toxicity to various agents
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Tracheostomy malfunction
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Upper limb fracture
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Vascular access complication
         subjects affected / exposed
    5 / 884 (0.57%)
         occurrences causally related to treatment / all
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    Vascular access malfunction
         subjects affected / exposed
    2 / 884 (0.23%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Vascular graft complication
         subjects affected / exposed
    2 / 884 (0.23%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Vascular graft occlusion
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Vascular injury
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Vascular pseudoaneurysm ruptured
         subjects affected / exposed
    2 / 884 (0.23%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Wound
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Wound dehiscence
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Congenital, familial and genetic disorders
    Congenital cystic kidney disease
         subjects affected / exposed
    4 / 884 (0.45%)
         occurrences causally related to treatment / all
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    Haemorrhagic arteriovenous malformation
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Porencephaly
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Cardiac disorders
    Acute coronary syndrome
         subjects affected / exposed
    2 / 884 (0.23%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Acute myocardial infarction
         subjects affected / exposed
    13 / 884 (1.47%)
         occurrences causally related to treatment / all
    0 / 13
         deaths causally related to treatment / all
    0 / 3
    Angina pectoris
         subjects affected / exposed
    8 / 884 (0.90%)
         occurrences causally related to treatment / all
    0 / 8
         deaths causally related to treatment / all
    0 / 0
    Angina unstable
         subjects affected / exposed
    4 / 884 (0.45%)
         occurrences causally related to treatment / all
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    Aortic valve incompetence
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Aortic valve stenosis
         subjects affected / exposed
    2 / 884 (0.23%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Atrial fibrillation
         subjects affected / exposed
    15 / 884 (1.70%)
         occurrences causally related to treatment / all
    0 / 15
         deaths causally related to treatment / all
    0 / 1
    Atrial flutter
         subjects affected / exposed
    3 / 884 (0.34%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    Atrioventricular block complete
         subjects affected / exposed
    4 / 884 (0.45%)
         occurrences causally related to treatment / all
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    Bradycardia
         subjects affected / exposed
    3 / 884 (0.34%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    Cardiac arrest
         subjects affected / exposed
    20 / 884 (2.26%)
         occurrences causally related to treatment / all
    0 / 21
         deaths causally related to treatment / all
    0 / 15
    Cardiac failure
         subjects affected / exposed
    2 / 884 (0.23%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Cardiac failure acute
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Cardiac failure congestive
         subjects affected / exposed
    8 / 884 (0.90%)
         occurrences causally related to treatment / all
    0 / 10
         deaths causally related to treatment / all
    0 / 0
    Cardiac valve disease
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Cardio-respiratory arrest
         subjects affected / exposed
    4 / 884 (0.45%)
         occurrences causally related to treatment / all
    0 / 5
         deaths causally related to treatment / all
    0 / 3
    Cardiogenic shock
         subjects affected / exposed
    2 / 884 (0.23%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 2
    Cardiomyopathy
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Coronary artery disease
         subjects affected / exposed
    7 / 884 (0.79%)
         occurrences causally related to treatment / all
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    Coronary artery stenosis
         subjects affected / exposed
    2 / 884 (0.23%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    Mitral valve incompetence
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Myocardial infarction
         subjects affected / exposed
    7 / 884 (0.79%)
         occurrences causally related to treatment / all
    0 / 7
         deaths causally related to treatment / all
    0 / 3
    Myocardial ischaemia
         subjects affected / exposed
    5 / 884 (0.57%)
         occurrences causally related to treatment / all
    0 / 5
         deaths causally related to treatment / all
    0 / 1
    Pericardial effusion
         subjects affected / exposed
    2 / 884 (0.23%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Pericarditis uraemic
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Sinus node dysfunction
         subjects affected / exposed
    2 / 884 (0.23%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Sinus tachycardia
         subjects affected / exposed
    2 / 884 (0.23%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Supraventricular tachycardia
         subjects affected / exposed
    3 / 884 (0.34%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    Ventricular tachycardia
         subjects affected / exposed
    2 / 884 (0.23%)
         occurrences causally related to treatment / all
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    Nervous system disorders
    Altered state of consciousness
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Aphasia
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Brain injury
         subjects affected / exposed
    2 / 884 (0.23%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 2
    Brain stem stroke
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Carotid artery occlusion
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Carotid artery stenosis
         subjects affected / exposed
    4 / 884 (0.45%)
         occurrences causally related to treatment / all
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    Carpal tunnel syndrome
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Cerebral haemorrhage
         subjects affected / exposed
    5 / 884 (0.57%)
         occurrences causally related to treatment / all
    0 / 5
         deaths causally related to treatment / all
    0 / 2
    Cerebral infarction
         subjects affected / exposed
    2 / 884 (0.23%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Cerebral ischaemia
         subjects affected / exposed
    2 / 884 (0.23%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Cerebrovascular accident
         subjects affected / exposed
    7 / 884 (0.79%)
         occurrences causally related to treatment / all
    0 / 7
         deaths causally related to treatment / all
    0 / 2
    Diabetic neuropathy
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Dizziness
         subjects affected / exposed
    3 / 884 (0.34%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    Dysaesthesia
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Dysarthria
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Encephalopathy
         subjects affected / exposed
    3 / 884 (0.34%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    Epilepsy
         subjects affected / exposed
    2 / 884 (0.23%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 1
    Facial paresis
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Haemorrhage intracranial
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Haemorrhagic stroke
         subjects affected / exposed
    3 / 884 (0.34%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    Headache
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Hypersomnia
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Hypoaesthesia
         subjects affected / exposed
    2 / 884 (0.23%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    Hypoxic-ischaemic encephalopathy
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Loss of consciousness
         subjects affected / exposed
    2 / 884 (0.23%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    Metabolic encephalopathy
         subjects affected / exposed
    3 / 884 (0.34%)
         occurrences causally related to treatment / all
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    Multiple sclerosis
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Neuritis cranial
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Normal pressure hydrocephalus
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Paraesthesia
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Presyncope
         subjects affected / exposed
    2 / 884 (0.23%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Quadriplegia
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Seizure
         subjects affected / exposed
    2 / 884 (0.23%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Syncope
         subjects affected / exposed
    13 / 884 (1.47%)
         occurrences causally related to treatment / all
    0 / 14
         deaths causally related to treatment / all
    0 / 0
    Transient global amnesia
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Transient ischaemic attack
         subjects affected / exposed
    4 / 884 (0.45%)
         occurrences causally related to treatment / all
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    Tremor
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Uraemic neuropathy
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    19 / 884 (2.15%)
         occurrences causally related to treatment / all
    0 / 26
         deaths causally related to treatment / all
    0 / 1
    Coagulopathy
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Haemorrhagic anaemia
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Nephrogenic anaemia
         subjects affected / exposed
    2 / 884 (0.23%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    Neutropenia
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Thrombocytopenia
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Ear and labyrinth disorders
    Vertigo
         subjects affected / exposed
    2 / 884 (0.23%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Eye disorders
    Cataract
         subjects affected / exposed
    2 / 884 (0.23%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    Optic ischaemic neuropathy
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Vision blurred
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Gastrointestinal disorders
    Abdominal hernia
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Abdominal pain
         subjects affected / exposed
    7 / 884 (0.79%)
         occurrences causally related to treatment / all
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    Abdominal pain upper
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Ascites
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Chronic gastritis
         subjects affected / exposed
    2 / 884 (0.23%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Colitis
         subjects affected / exposed
    3 / 884 (0.34%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    Colitis ischaemic
         subjects affected / exposed
    2 / 884 (0.23%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    Constipation
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Diarrhoea
         subjects affected / exposed
    7 / 884 (0.79%)
         occurrences causally related to treatment / all
    0 / 8
         deaths causally related to treatment / all
    0 / 0
    Diverticulum
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Diverticulum intestinal haemorrhagic
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Duodenal ulcer
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Duodenitis
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Enteritis
         subjects affected / exposed
    2 / 884 (0.23%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Epigastric discomfort
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Gastric ulcer
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Gastric ulcer haemorrhage
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Gastritis haemorrhagic
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Gastroduodenitis
         subjects affected / exposed
    2 / 884 (0.23%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Gastrointestinal haemorrhage
         subjects affected / exposed
    5 / 884 (0.57%)
         occurrences causally related to treatment / all
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    Haematemesis
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Haematochezia
         subjects affected / exposed
    3 / 884 (0.34%)
         occurrences causally related to treatment / all
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    Haemorrhagic erosive gastritis
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Haemorrhoidal haemorrhage
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Hernial eventration
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Ileus
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    Inguinal hernia
         subjects affected / exposed
    2 / 884 (0.23%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Intestinal ischaemia
         subjects affected / exposed
    2 / 884 (0.23%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    Intestinal obstruction
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Intestinal perforation
         subjects affected / exposed
    2 / 884 (0.23%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    Large intestinal obstruction
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Large intestine perforation
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Large intestine polyp
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Lower gastrointestinal haemorrhage
         subjects affected / exposed
    5 / 884 (0.57%)
         occurrences causally related to treatment / all
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    Nausea
         subjects affected / exposed
    4 / 884 (0.45%)
         occurrences causally related to treatment / all
    1 / 5
         deaths causally related to treatment / all
    0 / 0
    Oesophagitis
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Pancreatic disorder
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Pancreatitis
         subjects affected / exposed
    4 / 884 (0.45%)
         occurrences causally related to treatment / all
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    Pancreatitis acute
         subjects affected / exposed
    5 / 884 (0.57%)
         occurrences causally related to treatment / all
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    Pancreatitis chronic
         subjects affected / exposed
    2 / 884 (0.23%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Rectal haemorrhage
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Retroperitoneal haemorrhage
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Small intestine polyp
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Subileus
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Upper gastrointestinal haemorrhage
         subjects affected / exposed
    6 / 884 (0.68%)
         occurrences causally related to treatment / all
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    Vomiting
         subjects affected / exposed
    5 / 884 (0.57%)
         occurrences causally related to treatment / all
    1 / 6
         deaths causally related to treatment / all
    0 / 0
    Hepatobiliary disorders
    Acute hepatic failure
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Bile duct obstruction
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Bile duct stone
         subjects affected / exposed
    3 / 884 (0.34%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    Biliary colic
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Cholangitis
         subjects affected / exposed
    2 / 884 (0.23%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Cholecystitis acute
         subjects affected / exposed
    7 / 884 (0.79%)
         occurrences causally related to treatment / all
    0 / 7
         deaths causally related to treatment / all
    0 / 1
    Cholecystitis chronic
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Cholelithiasis
         subjects affected / exposed
    3 / 884 (0.34%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    Gallbladder disorder
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Hepatic cyst
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Hepatic cyst ruptured
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Jaundice
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Liver injury
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Sphincter of Oddi dysfunction
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Skin and subcutaneous tissue disorders
    Diabetic foot
         subjects affected / exposed
    2 / 884 (0.23%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    Skin discolouration
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Skin ulcer
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Renal and urinary disorders
    End stage renal disease
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Haematuria
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Hydronephrosis
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Nephrolithiasis
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Renal colic
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Renal cyst
         subjects affected / exposed
    2 / 884 (0.23%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    Renal cyst haemorrhage
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Renal failure
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Renal vein thrombosis
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Urethral stenosis
         subjects affected / exposed
    3 / 884 (0.34%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    Endocrine disorders
    Adrenal insufficiency
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Goitre
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Hyperparathyroidism secondary
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Hyperparathyroidism tertiary
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    6 / 884 (0.68%)
         occurrences causally related to treatment / all
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    Arthritis reactive
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Back pain
         subjects affected / exposed
    4 / 884 (0.45%)
         occurrences causally related to treatment / all
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    Cervical spinal stenosis
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Chondrocalcinosis
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Fracture nonunion
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Intervertebral disc degeneration
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Muscle spasms
         subjects affected / exposed
    2 / 884 (0.23%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Muscle swelling
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Muscular weakness
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Musculoskeletal chest pain
         subjects affected / exposed
    3 / 884 (0.34%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    Musculoskeletal pain
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Myalgia
         subjects affected / exposed
    2 / 884 (0.23%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Neck pain
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Neuropathic arthropathy
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Pain in extremity
         subjects affected / exposed
    6 / 884 (0.68%)
         occurrences causally related to treatment / all
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    Pseudarthrosis
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    SLE arthritis
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Spinal column stenosis
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Spinal osteoarthritis
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Tendon calcification
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Infections and infestations
    Abdominal abscess
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Abdominal wall abscess
         subjects affected / exposed
    2 / 884 (0.23%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Abscess limb
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Appendicitis
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Appendicitis perforated
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Arteriovenous fistula site infection
         subjects affected / exposed
    3 / 884 (0.34%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    Arteriovenous graft site abscess
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Arteriovenous graft site infection
         subjects affected / exposed
    3 / 884 (0.34%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    Arthritis bacterial
         subjects affected / exposed
    2 / 884 (0.23%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    Bacteraemia
         subjects affected / exposed
    3 / 884 (0.34%)
         occurrences causally related to treatment / all
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    Bacterial sepsis
         subjects affected / exposed
    2 / 884 (0.23%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Bronchitis
         subjects affected / exposed
    10 / 884 (1.13%)
         occurrences causally related to treatment / all
    0 / 11
         deaths causally related to treatment / all
    0 / 1
    Bronchitis bacterial
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Campylobacter gastroenteritis
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Catheter site infection
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    Cellulitis
         subjects affected / exposed
    9 / 884 (1.02%)
         occurrences causally related to treatment / all
    0 / 11
         deaths causally related to treatment / all
    0 / 0
    Cellulitis gangrenous
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Cellulitis orbital
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Citrobacter sepsis
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Clostridium difficile colitis
         subjects affected / exposed
    3 / 884 (0.34%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    Device related infection
         subjects affected / exposed
    7 / 884 (0.79%)
         occurrences causally related to treatment / all
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    Device related sepsis
         subjects affected / exposed
    4 / 884 (0.45%)
         occurrences causally related to treatment / all
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    Diabetic foot infection
         subjects affected / exposed
    2 / 884 (0.23%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Diabetic gangrene
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Diverticulitis
         subjects affected / exposed
    2 / 884 (0.23%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Ear infection
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Endocarditis
         subjects affected / exposed
    7 / 884 (0.79%)
         occurrences causally related to treatment / all
    0 / 7
         deaths causally related to treatment / all
    0 / 2
    Epiglottitis
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Erysipelas
         subjects affected / exposed
    2 / 884 (0.23%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Escherichia sepsis
         subjects affected / exposed
    2 / 884 (0.23%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Febrile infection
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Gangrene
         subjects affected / exposed
    9 / 884 (1.02%)
         occurrences causally related to treatment / all
    0 / 10
         deaths causally related to treatment / all
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    7 / 884 (0.79%)
         occurrences causally related to treatment / all
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    Helicobacter gastritis
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Hepatitis A
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Herpes zoster
         subjects affected / exposed
    3 / 884 (0.34%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    Infection
         subjects affected / exposed
    2 / 884 (0.23%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Influenza
         subjects affected / exposed
    3 / 884 (0.34%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    Intervertebral discitis
         subjects affected / exposed
    3 / 884 (0.34%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 1
    Intestinal tuberculosis
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Laryngitis
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Liver abscess
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Lower respiratory tract infection
         subjects affected / exposed
    4 / 884 (0.45%)
         occurrences causally related to treatment / all
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    Localised infection
         subjects affected / exposed
    3 / 884 (0.34%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    Lower respiratory tract infection viral
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Mediastinitis
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Meningitis
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Muscle abscess
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Orchitis
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Osteomyelitis
         subjects affected / exposed
    11 / 884 (1.24%)
         occurrences causally related to treatment / all
    0 / 11
         deaths causally related to treatment / all
    0 / 1
    Osteomyelitis chronic
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Perineal abscess
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Pneumonia
         subjects affected / exposed
    40 / 884 (4.52%)
         occurrences causally related to treatment / all
    0 / 48
         deaths causally related to treatment / all
    0 / 6
    Post procedural infection
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Postoperative wound infection
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Pseudomembranous colitis
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Pulmonary sepsis
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Pyelonephritis
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Respiratory tract infection
         subjects affected / exposed
    7 / 884 (0.79%)
         occurrences causally related to treatment / all
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    Respiratory tract infection viral
         subjects affected / exposed
    3 / 884 (0.34%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    Sepsis
         subjects affected / exposed
    27 / 884 (3.05%)
         occurrences causally related to treatment / all
    0 / 29
         deaths causally related to treatment / all
    0 / 8
    Septic shock
         subjects affected / exposed
    14 / 884 (1.58%)
         occurrences causally related to treatment / all
    0 / 14
         deaths causally related to treatment / all
    0 / 5
    Serratia bacteraemia
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Sinusitis
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Skin infection
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Staphylococcal bacteraemia
         subjects affected / exposed
    3 / 884 (0.34%)
         occurrences causally related to treatment / all
    0 / 5
         deaths causally related to treatment / all
    0 / 1
    Staphylococcal sepsis
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Stoma site infection
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Subcutaneous abscess
         subjects affected / exposed
    2 / 884 (0.23%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Systemic infection
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Tracheitis
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Tracheobronchitis
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    6 / 884 (0.68%)
         occurrences causally related to treatment / all
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    Urosepsis
         subjects affected / exposed
    3 / 884 (0.34%)
         occurrences causally related to treatment / all
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    Vascular access site infection
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Viral infection
         subjects affected / exposed
    2 / 884 (0.23%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Vulval abscess
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Wound infection
         subjects affected / exposed
    3 / 884 (0.34%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    Metabolism and nutrition disorders
    Calciphylaxis
         subjects affected / exposed
    2 / 884 (0.23%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    Dehydration
         subjects affected / exposed
    2 / 884 (0.23%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Electrolyte imbalance
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Fluid overload
         subjects affected / exposed
    16 / 884 (1.81%)
         occurrences causally related to treatment / all
    0 / 17
         deaths causally related to treatment / all
    0 / 0
    Fluid retention
         subjects affected / exposed
    2 / 884 (0.23%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Hyperglycaemia
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Hyperinsulinaemic hypoglycaemia
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Hyperkalaemia
         subjects affected / exposed
    16 / 884 (1.81%)
         occurrences causally related to treatment / all
    0 / 17
         deaths causally related to treatment / all
    0 / 0
    Hypervolaemia
         subjects affected / exposed
    2 / 884 (0.23%)
         occurrences causally related to treatment / all
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    Hypoglycaemia
         subjects affected / exposed
    4 / 884 (0.45%)
         occurrences causally related to treatment / all
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    Hyponatraemia
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Metabolic acidosis
         subjects affected / exposed
    1 / 884 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Etelcalcetide
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    537 / 884 (60.75%)
    Investigations
    Blood calcium decreased
         subjects affected / exposed
    253 / 884 (28.62%)
         occurrences all number
    408
    Injury, poisoning and procedural complications
    Arteriovenous fistula site complication
         subjects affected / exposed
    45 / 884 (5.09%)
         occurrences all number
    71
    Vascular disorders
    Hypertension
         subjects affected / exposed
    62 / 884 (7.01%)
         occurrences all number
    88
    Hypotension
         subjects affected / exposed
    60 / 884 (6.79%)
         occurrences all number
    108
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    84 / 884 (9.50%)
         occurrences all number
    112
    Nausea
         subjects affected / exposed
    58 / 884 (6.56%)
         occurrences all number
    70
    Vomiting
         subjects affected / exposed
    56 / 884 (6.33%)
         occurrences all number
    71
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    51 / 884 (5.77%)
         occurrences all number
    63
    Dyspnoea
         subjects affected / exposed
    50 / 884 (5.66%)
         occurrences all number
    63
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    52 / 884 (5.88%)
         occurrences all number
    58
    Muscle spasms
         subjects affected / exposed
    73 / 884 (8.26%)
         occurrences all number
    122
    Pain in extremity
         subjects affected / exposed
    59 / 884 (6.67%)
         occurrences all number
    85
    Infections and infestations
    Upper respiratory tract infection
         subjects affected / exposed
    58 / 884 (6.56%)
         occurrences all number
    73
    Viral upper respiratory tract infection
         subjects affected / exposed
    45 / 884 (5.09%)
         occurrences all number
    74
    Metabolism and nutrition disorders
    Hyperphosphataemia
         subjects affected / exposed
    82 / 884 (9.28%)
         occurrences all number
    99

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    21 May 2014
    The primary reason for the protocol amendment was both to create greater flexibility in dose titration in a real-world setting while recognizing differences in practice patterns across centers and regions and to standardize certain measurements. Changes to the protocol included: • A minimum monthly calcium and albumin was mandated because there are slight differences in standards of care globally for frequency of selected laboratory assays. These values allowed for a consistent calcium value to use in analyses. • Flexibility was allowed in the type of calcium measurement allowed (ie, corrected calcium or total calcium or ionized calcium equivalent) to inform dose titration. • The titration algorithm was modified to allow for increased flexibility for dose reductions in increments of 2.5 mg at the discretion of the investigator, based on corrected calcium values and not just parathyroid hormone values. • The titration algorithm was modified to allow for increased flexibility in the use of oral calcium supplements and the dialysate calcium bath. • The starting dose was modified only for subjects entering from Study 20120360 to 2.5 mg instead of 5 mg (all other subjects entered without a treatment gap from an open-label study, continuing on the same dose). • “Velcalcetide” was replaced with AMG 416.

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-Wed Apr 24 00:13:59 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA