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   44237   clinical trials with a EudraCT protocol, of which   7338   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:
    Pharmacokinetics of trimethoprim-sulfametrole in critically ill patients on continuous veno-venous haemofiltration

    Summary
    EudraCT number
    		 2014-003403-29
    Trial protocol
    		 AT  
    Global end of trial date
    11 Jun 2019

    Results information
    Results version number
    		 v1(current)
    This version publication date
    31 Jan 2021
    First version publication date
    31 Jan 2021
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    TMP-SMT-CVVH
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 -
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Medical University Innsbruck
    Sponsor organisation address
    Christoph-Probst-Platz 1, Innrain 52 A, Innsbruck, Austria, 6020
    Public contact
    Ao. Univ.Prof. Dr. Romuald Bellmann, Medical University Innsbruck, University Hospital for Internal Medicine I, 0043 51250481389, romuald.bellmann@i-med.ac.at
    Scientific contact
    Ao. Univ.Prof. Dr. Romuald Bellmann, Medical University Innsbruck, University Hospital for Internal Medicine I, 0043 51250481389, romuald.bellmann@i-med.ac.at
    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
    11 Jun 2019
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    11 Jun 2019
    Global end of trial reached?
    Yes
    Global end of trial date
    11 Jun 2019
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    Potential effects of continuous veno-venous haemofiltration on single and multiple dose pharmacokinetics of sulfametrole and trimethoprim were assessed.
    Protection of trial subjects
    Blood samples were drawn from an arterial or a venous line that had been inserted for diagnostics as part of routine management at the ICU. The blood volume needed for the study amounted 42 mL per study day, which is easily tolerated by adult patients. The risk of blood sampling from an arterial or a venous line by members of the ICU staff is very low. There is no risk by taking blood samples from the haemofilter inlet and outlet or from sampling ultrafiltrate. ICU monitoring was performed in all study patients.
    Background therapy
    		 Subjects received treatment of an intensive care unit due to their medical history. SMT-TMP was part of routine treatment according to clinical indication.
    Evidence for comparator
    		 There was no evidence for a comparator.
    Actual start date of recruitment
    01 Sep 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
    Austria: 24
    Worldwide total number of subjects
    24
    EEA total number of subjects
    24
    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)
    14
    From 65 to 84 years
    10
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 The study was performed at the Medical Emergency and Intensive Care Unit (Medical ICU) and at the Transplant ICU, Department of Anaesthesia and Critical Care, Centre of Operative Medicine, Innsbruck General Hospital. Adult critically ill patients (female and male) treated with TMP-SMT according to clinical indication were enrolled.

    Pre-assignment
    Screening details
    		 Patients at the participating ICUs on SMT-TMP treatment were screened. Patients on CRRT and patients not on CRRT with plasma creatinine < 1.5 mg/dl were eligible.

    Period 1
    Period 1 title
    Dosage interval period (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Non-randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    No

    Arm title
    		 CRRT group
    Arm description
    		 Adult critically ill patients treated with TMP-SMT (trimethoprim and sulfametrole) according to clinical indication were enrolled. The CRRT group comprised twelve consecutive patients with renal failure undergoing CVVH. Patients obtained TMP-SMT at standard doses recommended for the respective indications, since relevant elimination of both components by CVVH is anticipated. Plasma pharmacokinetics was determined after the first administration and at steady state.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Rokiprim
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    TMP-SMT was provided as a 250-ml infusion bottle containing 160 mg of TMP and 800 mg of SMT. TMP-SMT was applied intravenously at standard doses recommended for the respective indications (250 ml b.i.d. or t.i.d.). For treatment of Pneumocystis jirovecii pneumonia higher doses were required (15-20 mg/kg body weight of TMP per day divided in 3-4 doses which equals about 7 bottles of Rokiprim®). The infusion time Tinf was set to 30 minutes using an electronic infusion pump.

    Arm title
    		 Control group
    Arm description
    		 Adult critically ill patients treated with TMP-SMT (trimethoprim and sulfametrole) according to clinical indication were enrolled. Twelve critically ill patients on TMP-SMT treatment with approximately normal renal function were included in the control group. Patients obtained TMP-SMT at standard doses recommended for the respective indications. Plasma pharmacokinetics was determined after the first administration and at steady state.
    Arm type
    		 Control

    Investigational medicinal product name
    Rokiprim
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    TMP-SMT was provided as a 250-ml infusion bottle containing 160 mg of TMP and 800 mg of SMT. TMP-SMT was applied intravenously at standard doses recommended for the respective indications (250 ml b.i.d. or t.i.d.). For treatment of Pneumocystis jirovecii pneumonia higher doses were required (15-20 mg/kg body weight of TMP per day divided in 3-4 doses which equals about 7 bottles of Rokiprim®). The infusion time Tinf was set to 30 minutes using an electronic infusion pump.

    Number of subjects in period 1
    		CRRT group Control group
    Started
    12
    11
    Completed
    11
    12
    Not completed
    1
    0
         Transferred to other arm/group
    1
    -
    Joined
    0
    1
         Transferred in from other group/arm
    -
    1

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    CRRT group
    Reporting group description
    		 Adult critically ill patients treated with TMP-SMT (trimethoprim and sulfametrole) according to clinical indication were enrolled. The CRRT group comprised twelve consecutive patients with renal failure undergoing CVVH. Patients obtained TMP-SMT at standard doses recommended for the respective indications, since relevant elimination of both components by CVVH is anticipated. Plasma pharmacokinetics was determined after the first administration and at steady state.

    Reporting group title
    Control group
    Reporting group description
    		 Adult critically ill patients treated with TMP-SMT (trimethoprim and sulfametrole) according to clinical indication were enrolled. Twelve critically ill patients on TMP-SMT treatment with approximately normal renal function were included in the control group. Patients obtained TMP-SMT at standard doses recommended for the respective indications. Plasma pharmacokinetics was determined after the first administration and at steady state.

    Reporting group values
    		 CRRT group Control group Total
    Number of subjects
    		 12 12 24
    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)
    		 9 5 14
        From 65-84 years
    		 3 7 10
        85 years and over
    		 0 0 0
    Age continuous
    Units: years
        median (full range (min-max))
    		 61 (25 to 79) 67 (42 to 76) -
    Gender categorical
    Units: Subjects
        Female
    		 6 2 8
        Male
    		 6 10 16

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    CRRT group
    Reporting group description
    		 Adult critically ill patients treated with TMP-SMT (trimethoprim and sulfametrole) according to clinical indication were enrolled. The CRRT group comprised twelve consecutive patients with renal failure undergoing CVVH. Patients obtained TMP-SMT at standard doses recommended for the respective indications, since relevant elimination of both components by CVVH is anticipated. Plasma pharmacokinetics was determined after the first administration and at steady state.

    Reporting group title
    Control group
    Reporting group description
    		 Adult critically ill patients treated with TMP-SMT (trimethoprim and sulfametrole) according to clinical indication were enrolled. Twelve critically ill patients on TMP-SMT treatment with approximately normal renal function were included in the control group. Patients obtained TMP-SMT at standard doses recommended for the respective indications. Plasma pharmacokinetics was determined after the first administration and at steady state.

    Primary: AUC 0-n TMP

    		 Close Top of page
    End point title
    		 AUC 0-n TMP
    End point description
    AUC 0–n is defined as AUC 0–n from t=0 to t last, which was maximum 12h.
    End point type
    Primary
    End point timeframe
    Maximum 12 hours
    End point values
    		 CRRT group Control group
    Number of subjects analysed
    12
    12
    Units: mg.h/L
        median (full range (min-max))
    32 (8 to 114)
    35 (7 to 92)
    Statistical analysis title
    		 AUC 0-n TMP
    Comparison groups
    CRRT group v Control group
    Number of subjects included in analysis
    24
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.77
    Method
    		 Mann-Whitney-U-test
    Confidence interval

    Primary: AUC 0-n SMT

    		 Close Top of page
    End point title
    		 AUC 0-n SMT
    End point description
    AUC 0–n is defined as AUC 0–n from t=0 to t last, which was maximum 12h.
    End point type
    Primary
    End point timeframe
    Maximum 12 hours
    End point values
    		 CRRT group Control group
    Number of subjects analysed
    12
    12
    Units: mg.h/L
        median (full range (min-max))
    408 (163 to 1175)
    546 (208 to 1547)
    Statistical analysis title
    		 AUC 0-n SMT
    Comparison groups
    CRRT group v Control group
    Number of subjects included in analysis
    24
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.18
    Method
    		 Mann-Whitney-U-test
    Confidence interval

    Adverse events

    		 Close Top of page
    Adverse events information [1]
    Timeframe for reporting adverse events
    Day 0- day 3 or later, when approximate steady state conditions were assumed
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 CTCAE
    Dictionary version
    4.03
    Reporting groups
    Reporting group title
    CRRT group
    Reporting group description
    		 Adult critically ill patients treated with TMP-SMT (trimethoprim and sulfametrole) according to clinical indication were enrolled. The CRRT group comprised twelve consecutive patients with renal failure undergoing CVVH. Patients obtained TMP-SMT at standard doses recommended for the respective indications, since relevant elimination of both components by CVVH is anticipated. Plasma pharmacokinetics was determined after the first administration and at steady state.

    Reporting group title
    Control group
    Reporting group description
    		 Adult critically ill patients treated with TMP-SMT (trimethoprim and sulfametrole) according to clinical indication were enrolled. Twelve critically ill patients on TMP-SMT treatment with approximately normal renal function were included in the control group. Patients obtained TMP-SMT at standard doses recommended for the respective indications. Plasma pharmacokinetics was determined after the first administration and at steady state.

    Serious adverse events
    		 CRRT group Control group
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 12 (0.00%)
         number of deaths (all causes)
    0
    0
         number of deaths resulting from adverse events
    0
    0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 CRRT group Control group
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    Notes
    [1] - There are no non-serious adverse events recorded for these results. It is expected that there will be at least one non-serious adverse event reported.
    Justification: No AEs or SAEs were observed in this trial.

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    27 Mar 2015
    new ICF Versions
    16 Oct 2015
    Two additional Departments at Innsbruck Medical University take part in this trial (Department of General and Surgical Intensive Care Medicine, Center of Operative Medicine and Department of Internal Medicine III). Urine samples (10 mL) will be taken from all patients presenting with diuresis via urinary catheter.
    14 Apr 2016
    another sub investigator

    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

    Online references
    http://www.ncbi.nlm.nih.gov/pubmed/31990343
    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 © 1995-2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA