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   43861   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 Single-blinded, Randomized, Controlled, Comparative Phase III Study Evaluating the Safety and Effectiveness of EVARREST™ Fibrin Sealant Patch as an Adjunct to Hemostasis During Cardiovascular Surgery

    Summary
    EudraCT number
    		 2013-003464-31
    Trial protocol
    		 GB   BE  
    Global end of trial date
    23 Sep 2015

    Results information
    Results version number
    		 v1(current)
    This version publication date
    16 Jul 2017
    First version publication date
    16 Jul 2017
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    BIOS-13-004
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02040428
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    ETHICON , a Johnson & Johnson Company
    Sponsor organisation address
    Route 22 West , Somerville, United States, NJ 08876-0151
    Public contact
    Dr Leonie Rynn, Clinical Development, ETHICON, a Johnson & Johnson Company., 001 908-218-2492, lrynn1@its.jnj.com
    Scientific contact
    Dr Richard Kocharian, Medical Director , ETHICON, a Johnson & Johnson Company., 001 908-218-2013, rkochar1@ITS.JNJ.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
    02 Dec 2015
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    23 Sep 2015
    Global end of trial reached?
    Yes
    Global end of trial date
    23 Sep 2015
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The objective of this study was to evaluate the safety and effectiveness of the EVARREST™ Fibrin Sealant Patch as an adjunct to hemostasis during cardiovascular surgery.
    Protection of trial subjects
    The protocol and consent form were provided to the appriopriate Ethics Committee for approval . In adddition, an independant Data Monitoring Committee was established and had responsibility for evaluating the progress of the trial and assessing patient safety and data quality.
    Background therapy
    		 Not applicable
    Evidence for comparator
    		 TachoSil® Absorbable Fibrin Sealant Patch was used as the comparator and was applied according to it's approved label and instructions for use (IFU).
    Actual start date of recruitment
    13 Jan 2014
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    United Kingdom: 34
    Country: Number of subjects enrolled
    Belgium: 7
    Country: Number of subjects enrolled
    United States: 62
    Country: Number of subjects enrolled
    Australia: 33
    Country: Number of subjects enrolled
    Japan: 20
    Worldwide total number of subjects
    156
    EEA total number of subjects
    41
    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)
    79
    From 65 to 84 years
    77
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 The first patient was recruited on the 13 January 2014 and the last patient completed 23 September 2015.

    Pre-assignment
    Screening details
    		 Prospective patients were screened within 21 days prior to surgery. Prior to any study specific procedures, subjects were fully informed of all aspects of the study and asked to sign a consent form. In Japan, subjects ≥18 and <20 required to have their consent signed by the subject’s legal representative.

    Period 1
    Period 1 title
    Overall Trial (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Single blind
    Roles blinded
    		 Subject
    Blinding implementation details
    Actual treatment not discussed with the patient.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 EVARREST™ Fibrin Sealant Patch
    Arm description
    		 Investigational Product
    Arm type
    		 Experimental

    Investigational medicinal product name
    EVARREST™ Fibrin Sealant Patch
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Sealant matrix
    Routes of administration
    Topical use
    Dosage and administration details
    After identification of the TBS, EVARREST was to be trimmed to an appropriate size to cover the TBS, allowing sufficient overlap (1 to 2 cm) onto non-bleeding areas, and then placed over the TBS. After correct application had been verified, firm manual compression sufficient to stem all bleeding at the TBS was to be maintained for 3 minutes per the instructions for use. The surgeon could use a surgical sponge to assist in providing adequate pressure over the entire surface of the EVARREST patch. No more than four units (10.2 x 10.2 cm / 4 x 4 inches) of EVARREST were to be left implanted in subjects treated with EVARREST.

    Arm title
    		 TachoSil®
    Arm description
    		 Comparator product
    Arm type
    		 Active Comparator

    Investigational medicinal product name
    No investigational medicinal product assigned in this arm
    Number of subjects in period 1
    		EVARREST™ Fibrin Sealant Patch TachoSil®
    Started
    75
    81
    Completed
    70
    77
    Not completed
    5
    4
         Adverse event, serious fatal
    4
    3
         Consent withdrawn by subject
    1
    1

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    EVARREST™ Fibrin Sealant Patch
    Reporting group description
    		 Investigational Product

    Reporting group title
    TachoSil®
    Reporting group description
    		 Comparator product

    Reporting group values
    		 EVARREST™ Fibrin Sealant Patch TachoSil® Total
    Number of subjects
    		 75 81 156
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0
        Newborns (0-27 days)
    		 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0
        Children (2-11 years)
    		 0 0 0
        Adolescents (12-17 years)
    		 0 0 0
        Adults (18-64 years)
    		 0 0 0
        From 65-84 years
    		 0 0 0
        85 years and over
    		 0 0 0
        Adults (18-<50 years)
    		 14 12 26
        Adults (50-<65 years)
    		 21 32 53
        Adults (65-<75 years)
    		 22 25 47
        Adults (>=75 years)
    		 18 12 30
    Gender categorical
    Units: Subjects
        Female
    		 19 20 39
        Male
    		 56 61 117

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    EVARREST™ Fibrin Sealant Patch
    Reporting group description
    		 Investigational Product

    Reporting group title
    TachoSil®
    Reporting group description
    		 Comparator product

    Subject analysis set title
    Intent to Treat
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    Intent-to- treat set (ITT or full analysis set) consisting of all randomized subjects. Subjects who did not complete the procedure after randomization were to be considered as failures and included in the ITT analysis.

    Subject analysis set title
    Safety
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    Safety set consisting of all subjects on whom the study procedure was started.

    Subject analysis set title
    Per Protocol
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    All subjects in the ITT analysis set who had no major protocol violations.

    Primary: Hemostasis at the TBS at 3 minutes and maintence to chest wall closure.

    		 Close Top of page
    End point title
    		 Hemostasis at the TBS at 3 minutes and maintence to chest wall closure.
    End point description
    Hemostasis at the TBS at 3 minutes following treatment application and with no re‐bleeding requiring treatment at the TBS any time prior to initiation of final chest wall closure. Hemostasis is defined as no detectable bleeding at the TBS.
    End point type
    Primary
    End point timeframe
    Up to final chest wall closure
    End point values
    		 EVARREST™ Fibrin Sealant Patch TachoSil® Intent to Treat Per Protocol
    Number of subjects analysed
    75 [1]
    81 [2]
    156
    141
    Units: Percentage of successes
    76
    80
    156
    141
    Notes
    [1] - 31107 randomized to EVARREST received TachoSil, analysed in EVARREST ITT & in Tachosil for Safety
    [2] - 31107 randomized to EVARREST received TachoSil, analysed in EVARREST ITT & in Tachosil for Safety
    Statistical analysis title
    		 Primary Efficacy Endpoint
    Comparison groups
    EVARREST™ Fibrin Sealant Patch v TachoSil®
    Number of subjects included in analysis
    156
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0001
    Method
    		 Chi-squared
    Confidence interval

    Secondary: Hemostasis at the TBS at 6 minutes and maintence to final chest wall closure.

    		 Close Top of page
    End point title
    		 Hemostasis at the TBS at 6 minutes and maintence to final chest wall closure.
    End point description
    Hemostasis at the TBS at 6 minutes following treatment application and with no re‐bleeding requiring treatment at the TBS any time prior to initiation of final chest wall closure.
    End point type
    Secondary
    End point timeframe
    Hemostasis at the TBS at 6 minutes and maintence to final chest wall closure.
    End point values
    		 EVARREST™ Fibrin Sealant Patch TachoSil® Intent to Treat Per Protocol
    Number of subjects analysed
    75 [3]
    81 [4]
    156 [5]
    141
    Units: Percentage of successes
    76
    80
    156
    141
    Notes
    [3] - 31107 randomized to EVARREST received TachoSil, analysed in EVARREST ITT & in Tachosil for Safety
    [4] - 31107 randomized to EVARREST received TachoSil, analysed in EVARREST ITT & in Tachosil for Safety
    [5] - Subject 31107 was randomized to EVARREST and received TachoSil, subject was analysed in EVARREST
    Statistical analysis title
    		 Secondary Endpoint Analysis
    Comparison groups
    EVARREST™ Fibrin Sealant Patch v TachoSil®
    Number of subjects included in analysis
    156
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0046
    Method
    		 logistics model
    Parameter type
    		 Log odds ratio
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -
         upper limit
    		 -

    Secondary: Hemostasis at the TBS at 10 minutes and maintence to final chest wall closure.

    		 Close Top of page
    End point title
    		 Hemostasis at the TBS at 10 minutes and maintence to final chest wall closure.
    End point description
    Hemostasis at the TBS at 10 minutes following treatment application and with no re‐bleeding requiring treatment at the TBS any time prior to initiation of final chest wall closure.
    End point type
    Secondary
    End point timeframe
    Hemostasis at the TBS at 10 minutes and maintence to final chest wall closure
    End point values
    		 EVARREST™ Fibrin Sealant Patch TachoSil® Intent to Treat Per Protocol
    Number of subjects analysed
    75 [6]
    81 [7]
    156
    141
    Units: Percentage of successes
    76
    80
    156
    141
    Notes
    [6] - 31107 randomized to EVARREST received TachoSil, analysed in EVARREST ITT & in Tachosil for Safety
    [7] - 31107 randomized to EVARREST received TachoSil, analysed in EVARREST ITT & in Tachosil for Safety
    Statistical analysis title
    		 Secondary Endpoint Analysis
    Comparison groups
    EVARREST™ Fibrin Sealant Patch v TachoSil®
    Number of subjects included in analysis
    156
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0352
    Method
    		 logistics model
    Parameter type
    		 Log odds ratio
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -
         upper limit
    		 -

    Secondary: Incidence of re‐bleeding requiring treatment after initial establishment of TBS hemostasis at 3 minutes.

    		 Close Top of page
    End point title
    		 Incidence of re‐bleeding requiring treatment after initial establishment of TBS hemostasis at 3 minutes.
    End point description
    Incidence of re‐bleeding requiring treatment after initial establishment of TBS hemostasis at 3 minutes.
    End point type
    Secondary
    End point timeframe
    Incidence of re‐bleeding requiring treatment after initial establishment of TBS hemostasis at 3 minutes.
    End point values
    		 EVARREST™ Fibrin Sealant Patch TachoSil® Intent to Treat Per Protocol
    Number of subjects analysed
    75 [8]
    81 [9]
    156
    141
    Units: Percentage of successes
    76
    80
    156
    141
    Notes
    [8] - 31107 randomized to EVARREST received TachoSil, analysed in EVARREST ITT & in Tachosil for Safety
    [9] - 31107 randomized to EVARREST received TachoSil, analysed in EVARREST ITT & in Tachosil for Safety
    Statistical analysis title
    		 Secondary Endpoint Analysis
    Comparison groups
    EVARREST™ Fibrin Sealant Patch v TachoSil®
    Number of subjects included in analysis
    156
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0046 [10]
    Method
    		 Chi-squared
    Confidence interval
         sides
    2-sided
         lower limit
    		 -
         upper limit
    		 -
    Notes
    [10] - P-value noted above is for Haemostatic success at 6 mins

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    Adverse events (collected from time of randomization, throughout the follow-up period until approximately 60-days after the procedure)
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    15
    Reporting groups
    Reporting group title
    EVARREST™ Fibrin Sealant Patch
    Reporting group description
    		 -

    Reporting group title
    TachoSil® Fibrin Sealant Patch
    Reporting group description
    		 TachoSil® Fibrin Sealant Patch

    Serious adverse events
    		 EVARREST™ Fibrin Sealant Patch TachoSil® Fibrin Sealant Patch
    Total subjects affected by serious adverse events
         subjects affected / exposed
    31 / 75 (41.33%)
    34 / 81 (41.98%)
         number of deaths (all causes)
    4
    3
         number of deaths resulting from adverse events
    0
    0
    Vascular disorders
    Hypertension
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 81 (1.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Jugular vein thrombosis
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 81 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Venous thrombosis limb
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 81 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Chest pain
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 81 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Multi-organ Failure
         subjects affected / exposed
    2 / 75 (2.67%)
    1 / 81 (1.23%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Pyrexia
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 81 (1.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Systemic inflammatory response syndrome
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 81 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Acute respiratory failure
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 81 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 81 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemothorax
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 81 (1.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pleural effusion
         subjects affected / exposed
    6 / 75 (8.00%)
    7 / 81 (8.64%)
         occurrences causally related to treatment / all
    0 / 7
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumothorax
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 81 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 81 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Respiratory failure
         subjects affected / exposed
    3 / 75 (4.00%)
    3 / 81 (3.70%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 3
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Psychiatric disorders
    Delirium
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 81 (1.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Investigations
    Anticoagulation drug level above therapeutic
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 81 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    International normalised ratio fluctuation
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 81 (1.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Anastomotic haemorrhage
         subjects affected / exposed
    4 / 75 (5.33%)
    1 / 81 (1.23%)
         occurrences causally related to treatment / all
    3 / 4
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arterial injury
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 81 (1.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac procedure complication
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 81 (1.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Post procedural haemorrhage
         subjects affected / exposed
    3 / 75 (4.00%)
    3 / 81 (3.70%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Postoperative thoracic procedure complication
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 81 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Procedural complication
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 81 (1.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Subdural haemorrhage
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 81 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Myocardial depression
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 81 (1.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acute myocardial infarction
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 81 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Atrial fibrillation
         subjects affected / exposed
    7 / 75 (9.33%)
    8 / 81 (9.88%)
         occurrences causally related to treatment / all
    0 / 7
    0 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrial flutter
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 81 (1.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrioventricular block complete
         subjects affected / exposed
    2 / 75 (2.67%)
    1 / 81 (1.23%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac arrest
         subjects affected / exposed
    3 / 75 (4.00%)
    0 / 81 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac failure congestive
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 81 (1.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac tamponade
         subjects affected / exposed
    1 / 75 (1.33%)
    2 / 81 (2.47%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiogenic shock
         subjects affected / exposed
    3 / 75 (4.00%)
    0 / 81 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pericardial effusion
         subjects affected / exposed
    1 / 75 (1.33%)
    3 / 81 (3.70%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Right ventricular failure
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 81 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ventricular extrasystoles
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 81 (1.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Brain injury
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 81 (1.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebrovascular accident
         subjects affected / exposed
    1 / 75 (1.33%)
    2 / 81 (2.47%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    convulsion
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 81 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Grand mal convulsion
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 81 (1.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypoxic-ischaemic encephalopathy
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 81 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Presyncope
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 81 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    1 / 75 (1.33%)
    1 / 81 (1.23%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Coagulopathy
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 81 (1.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemolytic anaemia
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 81 (1.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thrombocytopenia
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 81 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Intestinal ischaemia
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 81 (1.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Subcutaneous emphysema
         subjects affected / exposed
    2 / 75 (2.67%)
    0 / 81 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    Renal failure
         subjects affected / exposed
    1 / 75 (1.33%)
    2 / 81 (2.47%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal failure acute
         subjects affected / exposed
    1 / 75 (1.33%)
    2 / 81 (2.47%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Appendicitis
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 81 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bacteraemia
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 81 (1.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    bronchopneumonia
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 81 (1.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 81 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    2 / 75 (2.67%)
    3 / 81 (3.70%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Postoperative wound infection
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 81 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory tract infection
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 81 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 81 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 81 (1.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Wound infection
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 81 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Hyperglycaemia
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 81 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyperkalaemia
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 81 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyponatraemia
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 81 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 EVARREST™ Fibrin Sealant Patch TachoSil® Fibrin Sealant Patch
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    73 / 75 (97.33%)
    80 / 81 (98.77%)
    Vascular disorders
    Arterial haemorrhage
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 81 (1.23%)
         occurrences all number
    0
    1
    Blood pressure fluctuation
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 81 (0.00%)
         occurrences all number
    1
    0
    Deep vein thrombosis
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 81 (1.23%)
         occurrences all number
    0
    2
    Haematoma
         subjects affected / exposed
    2 / 75 (2.67%)
    4 / 81 (4.94%)
         occurrences all number
    2
    4
    Haemodynamic instability
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 81 (0.00%)
         occurrences all number
    1
    0
    Hypertension
         subjects affected / exposed
    4 / 75 (5.33%)
    9 / 81 (11.11%)
         occurrences all number
    5
    9
    Hypotension
         subjects affected / exposed
    15 / 75 (20.00%)
    18 / 81 (22.22%)
         occurrences all number
    15
    18
    Iliac artery occlusion
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 81 (0.00%)
         occurrences all number
    1
    0
    Jugular vein thrombosis
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 81 (0.00%)
         occurrences all number
    1
    0
    Peripheral coldness
         subjects affected / exposed
    1 / 75 (1.33%)
    2 / 81 (2.47%)
         occurrences all number
    1
    2
    Thrombophlebitis superficial
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 81 (0.00%)
         occurrences all number
    1
    0
    Vasodilatation
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 81 (1.23%)
         occurrences all number
    0
    1
    Venous thrombosis limb
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 81 (0.00%)
         occurrences all number
    1
    0
    Surgical and medical procedures
    Thoracic cavity drainage
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 81 (1.23%)
         occurrences all number
    0
    1
    General disorders and administration site conditions
    Catheter site inflammation
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 81 (1.23%)
         occurrences all number
    0
    1
    Catheter site pain
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 81 (0.00%)
         occurrences all number
    1
    0
    Catheter site related reaction
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 81 (0.00%)
         occurrences all number
    1
    0
    Chest pain
         subjects affected / exposed
    5 / 75 (6.67%)
    3 / 81 (3.70%)
         occurrences all number
    8
    3
    Chills
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 81 (0.00%)
         occurrences all number
    1
    0
    Crepitations
         subjects affected / exposed
    1 / 75 (1.33%)
    2 / 81 (2.47%)
         occurrences all number
    1
    2
    Extravasation
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 81 (0.00%)
         occurrences all number
    1
    0
    Fatigue
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 81 (0.00%)
         occurrences all number
    1
    0
    Gait disturbance
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 81 (1.23%)
         occurrences all number
    0
    1
    Generalised oedema
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 81 (0.00%)
         occurrences all number
    1
    0
    Hypothermia
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 81 (0.00%)
         occurrences all number
    1
    0
    Implant site extravasation
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 81 (0.00%)
         occurrences all number
    1
    0
    Malaise
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 81 (1.23%)
         occurrences all number
    0
    1
    medical device complication
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 81 (0.00%)
         occurrences all number
    1
    0
    Multi-organ failure
         subjects affected / exposed
    2 / 75 (2.67%)
    1 / 81 (1.23%)
         occurrences all number
    2
    1
    Oedema
         subjects affected / exposed
    1 / 75 (1.33%)
    4 / 81 (4.94%)
         occurrences all number
    1
    4
    Oedema peripheral
         subjects affected / exposed
    5 / 75 (6.67%)
    13 / 81 (16.05%)
         occurrences all number
    5
    14
    Pain
         subjects affected / exposed
    9 / 75 (12.00%)
    11 / 81 (13.58%)
         occurrences all number
    11
    13
    Pyrexia
         subjects affected / exposed
    11 / 75 (14.67%)
    10 / 81 (12.35%)
         occurrences all number
    13
    11
    Secretion discharge
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 81 (1.23%)
         occurrences all number
    0
    1
    Systemic inflammatory response syndrome
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 81 (0.00%)
         occurrences all number
    1
    0
    Tenderness
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 81 (1.23%)
         occurrences all number
    0
    2
    Thirst
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 81 (1.23%)
         occurrences all number
    0
    1
    Immune system disorders
    Anaphylactic shock
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 81 (0.00%)
         occurrences all number
    1
    0
    Reproductive system and breast disorders
    Erectile dysfunction
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 81 (0.00%)
         occurrences all number
    1
    0
    Scrotal swelling
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 81 (0.00%)
         occurrences all number
    1
    0
    Respiratory, thoracic and mediastinal disorders
    Acute lung injury
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 81 (1.23%)
         occurrences all number
    0
    1
    Acute pulmonary oedema
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 81 (0.00%)
         occurrences all number
    1
    0
    Acute respiratory failure
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 81 (0.00%)
         occurrences all number
    1
    0
    Atelectasis
         subjects affected / exposed
    6 / 75 (8.00%)
    12 / 81 (14.81%)
         occurrences all number
    6
    13
    Bronchospasm
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 81 (1.23%)
         occurrences all number
    0
    1
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 81 (0.00%)
         occurrences all number
    1
    0
    Cough
         subjects affected / exposed
    4 / 75 (5.33%)
    6 / 81 (7.41%)
         occurrences all number
    4
    6
    Dysphonia
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 81 (0.00%)
         occurrences all number
    1
    0
    Dyspnoea
         subjects affected / exposed
    7 / 75 (9.33%)
    5 / 81 (6.17%)
         occurrences all number
    7
    5
    Epistaxis
         subjects affected / exposed
    1 / 75 (1.33%)
    2 / 81 (2.47%)
         occurrences all number
    1
    2
    Haemothorax
         subjects affected / exposed
    0 / 75 (0.00%)
    2 / 81 (2.47%)
         occurrences all number
    0
    2
    Hypoxia
         subjects affected / exposed
    2 / 75 (2.67%)
    1 / 81 (1.23%)
         occurrences all number
    2
    1
    Lung infiltration
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 81 (0.00%)
         occurrences all number
    1
    0
    Pleural effusion
         subjects affected / exposed
    24 / 75 (32.00%)
    22 / 81 (27.16%)
         occurrences all number
    29
    22
    Pneumonia aspiration
         subjects affected / exposed
    1 / 75 (1.33%)
    1 / 81 (1.23%)
         occurrences all number
    1
    1
    Pneumothorax
         subjects affected / exposed
    8 / 75 (10.67%)
    5 / 81 (6.17%)
         occurrences all number
    8
    5
    Pulmonary congestion
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 81 (0.00%)
         occurrences all number
    1
    0
    Pulmonary embolism
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 81 (0.00%)
         occurrences all number
    1
    0
    Pulmonary haemorrhage
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 81 (0.00%)
         occurrences all number
    1
    0
    Pulmonary hypertension
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 81 (0.00%)
         occurrences all number
    1
    0
    Pulmonary oedema
         subjects affected / exposed
    5 / 75 (6.67%)
    4 / 81 (4.94%)
         occurrences all number
    5
    4
    Respiratory failure
         subjects affected / exposed
    3 / 75 (4.00%)
    3 / 81 (3.70%)
         occurrences all number
    4
    3
    Wheezing
         subjects affected / exposed
    2 / 75 (2.67%)
    0 / 81 (0.00%)
         occurrences all number
    2
    0
    Psychiatric disorders
    Agitation
         subjects affected / exposed
    1 / 75 (1.33%)
    1 / 81 (1.23%)
         occurrences all number
    1
    1
    Anxiety
         subjects affected / exposed
    2 / 75 (2.67%)
    5 / 81 (6.17%)
         occurrences all number
    2
    5
    Confusional state
         subjects affected / exposed
    3 / 75 (4.00%)
    6 / 81 (7.41%)
         occurrences all number
    3
    6
    Delirium
         subjects affected / exposed
    3 / 75 (4.00%)
    7 / 81 (8.64%)
         occurrences all number
    3
    7
    Depression
         subjects affected / exposed
    1 / 75 (1.33%)
    1 / 81 (1.23%)
         occurrences all number
    1
    1
    Hallucination
         subjects affected / exposed
    3 / 75 (4.00%)
    0 / 81 (0.00%)
         occurrences all number
    3
    0
    Insomnia
         subjects affected / exposed
    1 / 75 (1.33%)
    9 / 81 (11.11%)
         occurrences all number
    1
    9
    Panic attack
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 81 (1.23%)
         occurrences all number
    0
    1
    Paranoia
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 81 (1.23%)
         occurrences all number
    0
    1
    Psychiatric symptom
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 81 (1.23%)
         occurrences all number
    0
    1
    Restlessness
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 81 (0.00%)
         occurrences all number
    2
    0
    Stress
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 81 (0.00%)
         occurrences all number
    1
    0
    Disorientation
         subjects affected / exposed
    2 / 75 (2.67%)
    2 / 81 (2.47%)
         occurrences all number
    2
    2
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 81 (1.23%)
         occurrences all number
    0
    1
    Anticoagulation drug level above therapeutic
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 81 (0.00%)
         occurrences all number
    1
    0
    Aspartate aminotransferase increased
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 81 (1.23%)
         occurrences all number
    0
    1
    Blood creatine increased
         subjects affected / exposed
    2 / 75 (2.67%)
    1 / 81 (1.23%)
         occurrences all number
    2
    1
    Blood electrolytes decreased
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 81 (1.23%)
         occurrences all number
    0
    1
    Blood fibrinogen increased
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 81 (1.23%)
         occurrences all number
    0
    1
    Blood glucose fluctuation
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 81 (1.23%)
         occurrences all number
    0
    1
    Blood lactic acid decreased
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 81 (0.00%)
         occurrences all number
    1
    0
    Blood lactic acid increased
         subjects affected / exposed
    1 / 75 (1.33%)
    1 / 81 (1.23%)
         occurrences all number
    1
    1
    Breath sounds abnormal
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 81 (1.23%)
         occurrences all number
    0
    1
    C-reactive protein increased
         subjects affected / exposed
    2 / 75 (2.67%)
    2 / 81 (2.47%)
         occurrences all number
    2
    2
    Cardiac murmur
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 81 (1.23%)
         occurrences all number
    0
    1
    Cardiac output decreased
         subjects affected / exposed
    2 / 75 (2.67%)
    1 / 81 (1.23%)
         occurrences all number
    3
    1
    Central venous pressure decreased
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 81 (0.00%)
         occurrences all number
    1
    0
    Chest X-ray abnormal
         subjects affected / exposed
    0 / 75 (0.00%)
    2 / 81 (2.47%)
         occurrences all number
    0
    2
    Electrocardiogram ST segment elevation
         subjects affected / exposed
    1 / 75 (1.33%)
    2 / 81 (2.47%)
         occurrences all number
    1
    2
    Enterococcus test positive
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 81 (1.23%)
         occurrences all number
    0
    1
    Haematocrit decreased
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 81 (1.23%)
         occurrences all number
    0
    1
    Heart rate decreased
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 81 (0.00%)
         occurrences all number
    1
    0
    Heart rate increased
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 81 (1.23%)
         occurrences all number
    0
    1
    Heart rate irregular
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 81 (0.00%)
         occurrences all number
    1
    0
    Inspiratory capacity decreased
         subjects affected / exposed
    2 / 75 (2.67%)
    3 / 81 (3.70%)
         occurrences all number
    2
    3
    International normalised ratio fluctuation
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 81 (1.23%)
         occurrences all number
    0
    1
    International normalised ratio increased
         subjects affected / exposed
    0 / 75 (0.00%)
    3 / 81 (3.70%)
         occurrences all number
    0
    3
    Klebsiella test positive
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 81 (1.23%)
         occurrences all number
    0
    1
    Liver function test abnormal
         subjects affected / exposed
    2 / 75 (2.67%)
    4 / 81 (4.94%)
         occurrences all number
    2
    4
    Neurological examination abnormal
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 81 (1.23%)
         occurrences all number
    0
    1
    Oxygen saturation decreased
         subjects affected / exposed
    3 / 75 (4.00%)
    1 / 81 (1.23%)
         occurrences all number
    3
    1
    Prothrombin time prolonged
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 81 (0.00%)
         occurrences all number
    1
    0
    Staphylococcus test positive
         subjects affected / exposed
    1 / 75 (1.33%)
    1 / 81 (1.23%)
         occurrences all number
    1
    1
    Thoracic cavity drainage test abnormal
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 81 (0.00%)
         occurrences all number
    1
    0
    Transaminases increased
         subjects affected / exposed
    1 / 75 (1.33%)
    1 / 81 (1.23%)
         occurrences all number
    1
    1
    Urine output decreased
         subjects affected / exposed
    3 / 75 (4.00%)
    4 / 81 (4.94%)
         occurrences all number
    3
    4
    Weight decreased
         subjects affected / exposed
    2 / 75 (2.67%)
    0 / 81 (0.00%)
         occurrences all number
    2
    0
    Weight increased
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 81 (0.00%)
         occurrences all number
    1
    0
    Injury, poisoning and procedural complications
    Anaemia postoperative
         subjects affected / exposed
    2 / 75 (2.67%)
    3 / 81 (3.70%)
         occurrences all number
    2
    3
    Anastomotic haemorrhage
         subjects affected / exposed
    4 / 75 (5.33%)
    1 / 81 (1.23%)
         occurrences all number
    4
    1
    Arterial injury
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 81 (1.23%)
         occurrences all number
    0
    1
    Cardiac procedure complication
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 81 (1.23%)
         occurrences all number
    0
    1
    Contusion
         subjects affected / exposed
    1 / 75 (1.33%)
    1 / 81 (1.23%)
         occurrences all number
    1
    1
    Donor site complication
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 81 (1.23%)
         occurrences all number
    0
    1
    Excoriation
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 81 (0.00%)
         occurrences all number
    1
    0
    Head injury
         subjects affected / exposed
    2 / 75 (2.67%)
    1 / 81 (1.23%)
         occurrences all number
    2
    1
    Injury corneal
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 81 (0.00%)
         occurrences all number
    1
    0
    Laceration
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 81 (1.23%)
         occurrences all number
    0
    1
    Limb injury
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 81 (0.00%)
         occurrences all number
    1
    0
    Mouth injury
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 81 (1.23%)
         occurrences all number
    0
    1
    Muscle strain
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 81 (0.00%)
         occurrences all number
    1
    0
    Post procedural haemorrhage
         subjects affected / exposed
    5 / 75 (6.67%)
    4 / 81 (4.94%)
         occurrences all number
    6
    4
    Post procedural persistant drain fluid
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 81 (0.00%)
         occurrences all number
    1
    0
    Postoperative thoracic procedure complication
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 81 (0.00%)
         occurrences all number
    1
    0
    Procedural complication
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 81 (1.23%)
         occurrences all number
    0
    1
    Procedural dizziness
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 81 (0.00%)
         occurrences all number
    1
    0
    Procedural pain
         subjects affected / exposed
    9 / 75 (12.00%)
    5 / 81 (6.17%)
         occurrences all number
    11
    7
    Seroma
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 81 (0.00%)
         occurrences all number
    1
    0
    Subdural haemorrhage
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 81 (0.00%)
         occurrences all number
    1
    0
    Suture related complication
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 81 (1.23%)
         occurrences all number
    0
    1
    Venous injury
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 81 (1.23%)
         occurrences all number
    0
    1
    Wound complication
         subjects affected / exposed
    3 / 75 (4.00%)
    9 / 81 (11.11%)
         occurrences all number
    3
    9
    Wound dehiscence
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 81 (1.23%)
         occurrences all number
    0
    1
    Wound secretion
         subjects affected / exposed
    3 / 75 (4.00%)
    3 / 81 (3.70%)
         occurrences all number
    3
    3
    Cardiac disorders
    Acute myocardial infarction
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 81 (0.00%)
         occurrences all number
    1
    0
    Arrhythmia
         subjects affected / exposed
    2 / 75 (2.67%)
    1 / 81 (1.23%)
         occurrences all number
    2
    1
    Arrhythmia supraventricular
         subjects affected / exposed
    0 / 75 (0.00%)
    2 / 81 (2.47%)
         occurrences all number
    0
    2
    Atrial fibrillation
         subjects affected / exposed
    34 / 75 (45.33%)
    29 / 81 (35.80%)
         occurrences all number
    35
    32
    Atrial flutter
         subjects affected / exposed
    2 / 75 (2.67%)
    2 / 81 (2.47%)
         occurrences all number
    2
    2
    Atrioventricular block
         subjects affected / exposed
    2 / 75 (2.67%)
    1 / 81 (1.23%)
         occurrences all number
    4
    1
    Atrioventricular block complete
         subjects affected / exposed
    2 / 75 (2.67%)
    1 / 81 (1.23%)
         occurrences all number
    2
    1
    Atrioventricular block first degree
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 81 (1.23%)
         occurrences all number
    0
    1
    Bradycardia
         subjects affected / exposed
    2 / 75 (2.67%)
    2 / 81 (2.47%)
         occurrences all number
    2
    2
    Bundle branch block left
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 81 (0.00%)
         occurrences all number
    1
    0
    Cardiac arrest
         subjects affected / exposed
    2 / 75 (2.67%)
    0 / 81 (0.00%)
         occurrences all number
    2
    0
    Cardiac failure
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 81 (1.23%)
         occurrences all number
    0
    1
    Cardiac failure congestive
         subjects affected / exposed
    4 / 75 (5.33%)
    1 / 81 (1.23%)
         occurrences all number
    4
    1
    Cardiac tamponade
         subjects affected / exposed
    1 / 75 (1.33%)
    2 / 81 (2.47%)
         occurrences all number
    1
    2
    Cardiogenic shock
         subjects affected / exposed
    3 / 75 (4.00%)
    0 / 81 (0.00%)
         occurrences all number
    3
    0
    Extrasystoles
         subjects affected / exposed
    1 / 75 (1.33%)
    1 / 81 (1.23%)
         occurrences all number
    1
    1
    Myocardial depression
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 81 (1.23%)
         occurrences all number
    0
    1
    Nodal rhythm
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 81 (0.00%)
         occurrences all number
    1
    0
    Palpitations
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 81 (0.00%)
         occurrences all number
    1
    0
    Pericardial effusion
         subjects affected / exposed
    1 / 75 (1.33%)
    8 / 81 (9.88%)
         occurrences all number
    1
    8
    Pericarditis
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 81 (1.23%)
         occurrences all number
    0
    1
    Postural orthostatic tachycardia syndrome
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 81 (0.00%)
         occurrences all number
    1
    0
    Right ventricular failure
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 81 (0.00%)
         occurrences all number
    1
    0
    Sinus bradycardia
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 81 (1.23%)
         occurrences all number
    0
    1
    Supraventricular extrasystoles
         subjects affected / exposed
    1 / 75 (1.33%)
    1 / 81 (1.23%)
         occurrences all number
    1
    1
    Tachyarrhythmia
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 81 (0.00%)
         occurrences all number
    1
    0
    Tachycardia
         subjects affected / exposed
    3 / 75 (4.00%)
    5 / 81 (6.17%)
         occurrences all number
    3
    5
    Trifascicular block
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 81 (1.23%)
         occurrences all number
    0
    1
    Ventricular extrasystoles
         subjects affected / exposed
    1 / 75 (1.33%)
    1 / 81 (1.23%)
         occurrences all number
    1
    1
    Ventricular fibrillation
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 81 (0.00%)
         occurrences all number
    1
    0
    Ventricular tachycardia
         subjects affected / exposed
    3 / 75 (4.00%)
    1 / 81 (1.23%)
         occurrences all number
    3
    1
    Nervous system disorders
    Balance disorder
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 81 (1.23%)
         occurrences all number
    0
    1
    Brain injury
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 81 (1.23%)
         occurrences all number
    0
    1
    Cerebrovascular accident
         subjects affected / exposed
    1 / 75 (1.33%)
    2 / 81 (2.47%)
         occurrences all number
    1
    2
    convulsion
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 81 (0.00%)
         occurrences all number
    1
    0
    Cubital tunnel syndrome
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 81 (1.23%)
         occurrences all number
    0
    1
    Dementia
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 81 (1.23%)
         occurrences all number
    0
    1
    Dizziness
         subjects affected / exposed
    5 / 75 (6.67%)
    3 / 81 (3.70%)
         occurrences all number
    5
    3
    encephalopathy
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 81 (1.23%)
         occurrences all number
    0
    1
    Epilepsy
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 81 (0.00%)
         occurrences all number
    1
    0
    Grand Mal convulsion
         subjects affected / exposed
    1 / 75 (1.33%)
    1 / 81 (1.23%)
         occurrences all number
    1
    1
    Headache
         subjects affected / exposed
    2 / 75 (2.67%)
    0 / 81 (0.00%)
         occurrences all number
    2
    0
    Hemiparesis
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 81 (1.23%)
         occurrences all number
    0
    1
    Hypoaesthesia
         subjects affected / exposed
    0 / 75 (0.00%)
    2 / 81 (2.47%)
         occurrences all number
    0
    2
    Hypoxic-ischaemic encephalopathy
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 81 (0.00%)
         occurrences all number
    1
    0
    Lethargy
         subjects affected / exposed
    1 / 75 (1.33%)
    1 / 81 (1.23%)
         occurrences all number
    1
    1
    Loss of consciousness
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 81 (1.23%)
         occurrences all number
    0
    1
    Migraine
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 81 (0.00%)
         occurrences all number
    1
    0
    Neuralgia
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 81 (1.23%)
         occurrences all number
    0
    1
    Neuropathy peripheral
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 81 (0.00%)
         occurrences all number
    1
    0
    Paraesthesia
         subjects affected / exposed
    1 / 75 (1.33%)
    1 / 81 (1.23%)
         occurrences all number
    1
    2
    Presyncope
         subjects affected / exposed
    2 / 75 (2.67%)
    0 / 81 (0.00%)
         occurrences all number
    2
    0
    Somnolence
         subjects affected / exposed
    1 / 75 (1.33%)
    2 / 81 (2.47%)
         occurrences all number
    1
    2
    Syncope
         subjects affected / exposed
    0 / 75 (0.00%)
    2 / 81 (2.47%)
         occurrences all number
    0
    2
    Tremor
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 81 (0.00%)
         occurrences all number
    1
    0
    Vocal cord paralysis
         subjects affected / exposed
    0 / 75 (0.00%)
    2 / 81 (2.47%)
         occurrences all number
    0
    2
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    18 / 75 (24.00%)
    21 / 81 (25.93%)
         occurrences all number
    18
    22
    Coagulopathy
         subjects affected / exposed
    3 / 75 (4.00%)
    4 / 81 (4.94%)
         occurrences all number
    3
    4
    Haemolytic anaemia
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 81 (1.23%)
         occurrences all number
    0
    1
    Haemorrhagic anaemia
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 81 (0.00%)
         occurrences all number
    1
    0
    Leukocytosis
         subjects affected / exposed
    2 / 75 (2.67%)
    4 / 81 (4.94%)
         occurrences all number
    2
    4
    Lymphopenia
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 81 (1.23%)
         occurrences all number
    0
    1
    Normochromic normocytic anaemia
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 81 (0.00%)
         occurrences all number
    1
    0
    Thrombocytopenia
         subjects affected / exposed
    7 / 75 (9.33%)
    7 / 81 (8.64%)
         occurrences all number
    7
    7
    Ear and labyrinth disorders
    Ear pain
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 81 (1.23%)
         occurrences all number
    0
    1
    Meniere's disease
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 81 (0.00%)
         occurrences all number
    1
    0
    Eye disorders
    Diplopia
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 81 (1.23%)
         occurrences all number
    0
    1
    Eye pain
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 81 (0.00%)
         occurrences all number
    1
    0
    Miosis
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 81 (1.23%)
         occurrences all number
    0
    1
    Vision blurred
         subjects affected / exposed
    2 / 75 (2.67%)
    0 / 81 (0.00%)
         occurrences all number
    2
    0
    Visual impairment
         subjects affected / exposed
    2 / 75 (2.67%)
    1 / 81 (1.23%)
         occurrences all number
    2
    1
    Gastrointestinal disorders
    Abdominal distension
         subjects affected / exposed
    1 / 75 (1.33%)
    1 / 81 (1.23%)
         occurrences all number
    1
    1
    Abdominal pain
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 81 (0.00%)
         occurrences all number
    1
    0
    Abdominal wall haematoma
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 81 (1.23%)
         occurrences all number
    0
    1
    Constipation
         subjects affected / exposed
    15 / 75 (20.00%)
    15 / 81 (18.52%)
         occurrences all number
    17
    18
    Diarrhoea
         subjects affected / exposed
    8 / 75 (10.67%)
    2 / 81 (2.47%)
         occurrences all number
    9
    2
    Dyspepsia
         subjects affected / exposed
    1 / 75 (1.33%)
    2 / 81 (2.47%)
         occurrences all number
    1
    2
    Dysphagia
         subjects affected / exposed
    0 / 75 (0.00%)
    2 / 81 (2.47%)
         occurrences all number
    0
    2
    Gastrointestinal haemorrhage
         subjects affected / exposed
    2 / 75 (2.67%)
    0 / 81 (0.00%)
         occurrences all number
    2
    0
    Gastrooesophageal reflux disease
         subjects affected / exposed
    2 / 75 (2.67%)
    4 / 81 (4.94%)
         occurrences all number
    2
    4
    Haematemesis
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 81 (0.00%)
         occurrences all number
    1
    0
    Haematochezia
         subjects affected / exposed
    1 / 75 (1.33%)
    1 / 81 (1.23%)
         occurrences all number
    1
    1
    Haemorrhoids
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 81 (0.00%)
         occurrences all number
    1
    0
    Ileus
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 81 (1.23%)
         occurrences all number
    0
    1
    Intestinal ischaemia
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 81 (1.23%)
         occurrences all number
    0
    1
    Loose tooth
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 81 (1.23%)
         occurrences all number
    0
    1
    Mouth haemorrhage
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 81 (0.00%)
         occurrences all number
    1
    0
    Nausea
         subjects affected / exposed
    19 / 75 (25.33%)
    20 / 81 (24.69%)
         occurrences all number
    24
    23
    Oral mucosal erythema
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 81 (0.00%)
         occurrences all number
    1
    0
    Rectal haemorrhage
         subjects affected / exposed
    1 / 75 (1.33%)
    1 / 81 (1.23%)
         occurrences all number
    1
    1
    Stomatitis
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 81 (1.23%)
         occurrences all number
    0
    1
    Tongue discolouration
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 81 (1.23%)
         occurrences all number
    0
    1
    Tongue oedema
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 81 (1.23%)
         occurrences all number
    0
    1
    Vomiting
         subjects affected / exposed
    5 / 75 (6.67%)
    7 / 81 (8.64%)
         occurrences all number
    5
    8
    Hepatobiliary disorders
    Cholecystitis
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 81 (0.00%)
         occurrences all number
    1
    0
    Cholelithiasis
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 81 (0.00%)
         occurrences all number
    1
    0
    Hepatitis acute
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 81 (0.00%)
         occurrences all number
    1
    0
    Hyperbilirubinaemia
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 81 (0.00%)
         occurrences all number
    1
    0
    Ischaemic hepatitis
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 81 (0.00%)
         occurrences all number
    2
    0
    Jaundice
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 81 (1.23%)
         occurrences all number
    0
    1
    Skin and subcutaneous tissue disorders
    Blister
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 81 (1.23%)
         occurrences all number
    0
    1
    Decubitus ulcer
         subjects affected / exposed
    1 / 75 (1.33%)
    1 / 81 (1.23%)
         occurrences all number
    1
    1
    Erythema
         subjects affected / exposed
    2 / 75 (2.67%)
    2 / 81 (2.47%)
         occurrences all number
    2
    2
    Night sweats
         subjects affected / exposed
    1 / 75 (1.33%)
    1 / 81 (1.23%)
         occurrences all number
    1
    1
    Pruritus
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 81 (1.23%)
         occurrences all number
    0
    1
    Rash
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 81 (1.23%)
         occurrences all number
    0
    1
    Skin exfoliation
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 81 (1.23%)
         occurrences all number
    0
    1
    Subcutaneous emphysema
         subjects affected / exposed
    3 / 75 (4.00%)
    1 / 81 (1.23%)
         occurrences all number
    3
    1
    Renal and urinary disorders
    Haematuria
         subjects affected / exposed
    0 / 75 (0.00%)
    2 / 81 (2.47%)
         occurrences all number
    0
    2
    Haemorrhage urinary tract
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 81 (1.23%)
         occurrences all number
    0
    1
    Pollakiuria
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 81 (0.00%)
         occurrences all number
    1
    0
    Renal Failure
         subjects affected / exposed
    2 / 75 (2.67%)
    3 / 81 (3.70%)
         occurrences all number
    2
    3
    Renal failure acute
         subjects affected / exposed
    3 / 75 (4.00%)
    5 / 81 (6.17%)
         occurrences all number
    4
    5
    Renal impairment
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 81 (0.00%)
         occurrences all number
    1
    0
    Urinary incontinence
         subjects affected / exposed
    1 / 75 (1.33%)
    1 / 81 (1.23%)
         occurrences all number
    1
    1
    Urinary retention
         subjects affected / exposed
    1 / 75 (1.33%)
    2 / 81 (2.47%)
         occurrences all number
    1
    2
    Endocrine disorders
    Hyperthyroidism
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 81 (1.23%)
         occurrences all number
    0
    1
    Hypothyroidism
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 81 (1.23%)
         occurrences all number
    0
    1
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    1 / 75 (1.33%)
    1 / 81 (1.23%)
         occurrences all number
    1
    1
    Back pain
         subjects affected / exposed
    1 / 75 (1.33%)
    2 / 81 (2.47%)
         occurrences all number
    1
    2
    Joint stiffness
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 81 (1.23%)
         occurrences all number
    0
    1
    Limb discomfort
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 81 (0.00%)
         occurrences all number
    1
    0
    Muscle spasms
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 81 (0.00%)
         occurrences all number
    1
    0
    Muscular weakness
         subjects affected / exposed
    1 / 75 (1.33%)
    1 / 81 (1.23%)
         occurrences all number
    1
    1
    Musculoskeletal pain
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 81 (0.00%)
         occurrences all number
    1
    0
    Neck pain
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 81 (0.00%)
         occurrences all number
    1
    0
    Pain in extremity
         subjects affected / exposed
    2 / 75 (2.67%)
    1 / 81 (1.23%)
         occurrences all number
    2
    1
    Infections and infestations
    Appendicitis
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 81 (0.00%)
         occurrences all number
    1
    0
    aspergillosis
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 81 (1.23%)
         occurrences all number
    0
    1
    Bacteraemia
         subjects affected / exposed
    1 / 75 (1.33%)
    1 / 81 (1.23%)
         occurrences all number
    1
    1
    bronchopneumonia
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 81 (1.23%)
         occurrences all number
    0
    1
    candidiasis
         subjects affected / exposed
    2 / 75 (2.67%)
    1 / 81 (1.23%)
         occurrences all number
    2
    1
    Cellulitis
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 81 (0.00%)
         occurrences all number
    1
    0
    Cystitis
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 81 (0.00%)
         occurrences all number
    1
    0
    Escherichia infection
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 81 (0.00%)
         occurrences all number
    1
    0
    Fungal skin infection
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 81 (0.00%)
         occurrences all number
    1
    0
    Gastroenteritis viral
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 81 (1.23%)
         occurrences all number
    0
    1
    Graft infection
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 81 (1.23%)
         occurrences all number
    0
    1
    Haemophilus infection
         subjects affected / exposed
    2 / 75 (2.67%)
    0 / 81 (0.00%)
         occurrences all number
    2
    0
    Lower respiratory tract infection
         subjects affected / exposed
    2 / 75 (2.67%)
    3 / 81 (3.70%)
         occurrences all number
    2
    3
    Nasopharyngitis
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 81 (1.23%)
         occurrences all number
    0
    1
    Pneumonia
         subjects affected / exposed
    5 / 75 (6.67%)
    4 / 81 (4.94%)
         occurrences all number
    5
    4
    Postoperative wound infection
         subjects affected / exposed
    1 / 75 (1.33%)
    1 / 81 (1.23%)
         occurrences all number
    1
    1
    Respiratory tract infection
         subjects affected / exposed
    3 / 75 (4.00%)
    3 / 81 (3.70%)
         occurrences all number
    3
    3
    Sepsis
         subjects affected / exposed
    3 / 75 (4.00%)
    1 / 81 (1.23%)
         occurrences all number
    3
    1
    Sputum purulent
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 81 (0.00%)
         occurrences all number
    1
    0
    Staphylococcal infection
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 81 (0.00%)
         occurrences all number
    1
    0
    tooth abcess
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 81 (0.00%)
         occurrences all number
    1
    0
    Upper respiratory tract infection
         subjects affected / exposed
    2 / 75 (2.67%)
    0 / 81 (0.00%)
         occurrences all number
    2
    0
    Urinary tract infection
         subjects affected / exposed
    9 / 75 (12.00%)
    5 / 81 (6.17%)
         occurrences all number
    9
    5
    wound infection
         subjects affected / exposed
    4 / 75 (5.33%)
    4 / 81 (4.94%)
         occurrences all number
    4
    5
    Metabolism and nutrition disorders
    Acidosis
         subjects affected / exposed
    2 / 75 (2.67%)
    0 / 81 (0.00%)
         occurrences all number
    2
    0
    Decreased appetite
         subjects affected / exposed
    2 / 75 (2.67%)
    2 / 81 (2.47%)
         occurrences all number
    2
    2
    Dehydration
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 81 (0.00%)
         occurrences all number
    1
    0
    Electrolyte imbalance
         subjects affected / exposed
    2 / 75 (2.67%)
    1 / 81 (1.23%)
         occurrences all number
    2
    1
    Fluid imbalance
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 81 (0.00%)
         occurrences all number
    1
    0
    Fluid overload
         subjects affected / exposed
    12 / 75 (16.00%)
    11 / 81 (13.58%)
         occurrences all number
    13
    12
    Fluid retention
         subjects affected / exposed
    2 / 75 (2.67%)
    0 / 81 (0.00%)
         occurrences all number
    2
    0
    Gout
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 81 (0.00%)
         occurrences all number
    1
    0
    Hyperglycaemia
         subjects affected / exposed
    11 / 75 (14.67%)
    11 / 81 (13.58%)
         occurrences all number
    11
    11
    Hyperkalaemia
         subjects affected / exposed
    6 / 75 (8.00%)
    2 / 81 (2.47%)
         occurrences all number
    7
    2
    Hypermagnesaemia
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 81 (1.23%)
         occurrences all number
    0
    1
    Hypernatraemia
         subjects affected / exposed
    3 / 75 (4.00%)
    0 / 81 (0.00%)
         occurrences all number
    3
    0
    Hypoalbuminaemia
         subjects affected / exposed
    0 / 75 (0.00%)
    2 / 81 (2.47%)
         occurrences all number
    0
    2
    Hypocalcaemia
         subjects affected / exposed
    6 / 75 (8.00%)
    4 / 81 (4.94%)
         occurrences all number
    6
    4
    Hypoglycaemia
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 81 (0.00%)
         occurrences all number
    1
    0
    Hypokalaemia
         subjects affected / exposed
    7 / 75 (9.33%)
    7 / 81 (8.64%)
         occurrences all number
    8
    8
    Hypomagnesaemia
         subjects affected / exposed
    3 / 75 (4.00%)
    5 / 81 (6.17%)
         occurrences all number
    3
    5
    Hyponatraemia
         subjects affected / exposed
    5 / 75 (6.67%)
    1 / 81 (1.23%)
         occurrences all number
    5
    1
    Hypophosphataemia
         subjects affected / exposed
    6 / 75 (8.00%)
    3 / 81 (3.70%)
         occurrences all number
    6
    3
    Hypovolaemia
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 81 (0.00%)
         occurrences all number
    1
    0
    Malnutrition
         subjects affected / exposed
    0 / 75 (0.00%)
    2 / 81 (2.47%)
         occurrences all number
    0
    2
    Metabolic acidosis
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 81 (0.00%)
         occurrences all number
    1
    0
    Metabolic alkalosis
         subjects affected / exposed
    1 / 75 (1.33%)
    0 / 81 (0.00%)
         occurrences all number
    1
    0

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    20 Sep 2013
    Amendment 1 modified the stopping rule relating to treatment-related post-operative bleeding at the TBS, to clarify that this was only to apply to subjects in the EVARREST treatment group. This amendment was made before the start of subject recruitment.
    18 Aug 2014
    Amendment 2 deleted a stopping rule that had been included in the phase 2 protocol 400-12-002 but was not appropriate for the phase 3 study. The rule stated that the study should be stopped if three subjects in the EVARREST treatment arm had an intra-operative TBS re-bleeding event after 10 minutes post-application and prior to final chest wall closure that required re-intervention. The Phase 3 study design assumes 80% of EVARREST subjects will be successful; thus the failure rate assumed in the study is well above the three occurrence outlined in this stopping rule. This stopping rule was invoked on one occasion prior to implementation of Amendment 2.
    19 Jan 2015
    The principal change in amendment 3 was the clarification that the TBS could be identified during any reperfusion of the arterial anastomoses and not just the first. In addition the Amendment 3 allowed heparin reversal and removal from cardiopulmonary bypass any time after product application as well as clarifying retreatment due to product failure. Names and roles of study personnel were also updated and a number of clarifications made to protocol wording.

    Interruptions (globally)
    Were there any global interruptions to the trial? Yes
    Date
    Interruption
    Restart date
    21 Aug 2014
    On 21 August 2014 one of the stopping rules was met due to a subject 16101 developing post-operative bleeding at the Target Bleeding Site (TBS) in the EVARREST treatment arm as per protocol administrative change 1, dated 22Jan2014. This stopping rule triggered a temporary halt of the trial in all study regions (United States, Australia, Japan, and EU). The DMC met on 05 September 2014 to review this specific event as well as overall safety data for the trial. The DMC recommendation was to continue the trial unmodified and the temporary enrollment halt was lifted on 08 September 2014.
    08 Sep 2014
    18 Nov 2014
    On 18 November 2014 one of the stopping rules was met The stopping rule met was the following: three subjects in the EVARREST treatment arm had an intra‐operative TBS re‐bleeding event after 10 minutes post‐application and prior to final chest wall closure that required re‐intervention. The US was the only study region impacted by this temporary halt because this stopping rule was predefined in the protocol administrative change 1, dated 22Jan2014. The other study regions - EU, Australia and Japan - were not impacted by this stopping rule since these regions were approved to conduct the study as per Protocol Amendment 2, dated 18 August 2014. This stopping rule was removed from protocol amendment 2, dated 18 August 2014 (see Section 9.8). The DMC met on 24 November 2014 to review three intra-operative TBS re-bleeding events. The DMC recommendation for the second temporary halt was to continue the trial unmodified and the temporary halt was lifted on 28 November 2014 in the US.
    28 Nov 2014
    09 Dec 2014
    On 09 December 2014 the third temporary study halt was due to a subject in the EVARREST treatment arm developing post-operative bleeding at the (TBS) as per the stopping rule in protocol Amendment 2, dated 18 August 2014. All study regions were impacted by this temporary halt in order for the DMC to assess the event of Anastomotic Hemorrhage (Subject 31109) and overall safety data for the study. The DMC met on 23 December 2014 and 02 January 2015. The third temporary halt was lifted on 08 January 2015. The DMC also agreed with the Sponsor’s proposal to proceed with training and technical support provided to new product users. The protocol was also amended (Amendment 3, 19 January 2015) to allow heparin reversal and removal from cardiopulmonary bypass any time after product application as well as clarifying retreatment due to product failure.
    08 Jan 2015

    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-Thu Apr 25 16:40:43 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA