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   43873   clinical trials with a EudraCT protocol, of which   7293   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:
    Does oral administration of dabigatran etexilate, a direct thrombin inhibitor, achieve clinical significant concentrations of dabigatran and thrombin inhibiting activity in vitreous and subretinal fluid?

    Summary
    EudraCT number
    		 2014-000388-41
    Trial protocol
    		 NL  
    Global end of trial date
    22 Apr 2015

    Results information
    Results version number
    		 v2(current)
    This version publication date
    27 Jul 2019
    First version publication date
    03 Feb 2016
    Other versions
    		 v1
    Version creation reason
    • Changes to summary attachments
    pubmed link attached

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    OZR-2013-27
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 -
    WHO universal trial number (UTN)
    		 -
    Other trial identifiers
    		 Nederlands Trial Register: NTR4825
    Sponsors
    Sponsor organisation name
    The Rotterdam Eye Hospital
    Sponsor organisation address
    PO Box 70030, Rotterdam, Netherlands, 3000LM
    Public contact
    Rotterdam Ophthalmic Institute, The Rotterdam Eye Hospital, 31 104023430, r.wubbels@oogziekenhuis.nl
    Scientific contact
    Rotterdam Ophthalmic Institute, The Rotterdam Eye Hospital, 31 104023430, r.wubbels@oogziekenhuis.nl
    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
    21 May 2015
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    22 Apr 2015
    Global end of trial reached?
    Yes
    Global end of trial date
    22 Apr 2015
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    Quantifying dabigatran levels and thrombin inhibiting activity in the vitreous and subretinal fluid after oral administration of dabigatran etexilate in patiens with a retinal detachment.
    Protection of trial subjects
    Patients at increased risk of bleeding were excluded.
    Background therapy
    		 Coagulation factor thrombin is thought to play an important role in the development of proliferative vitreoretinopathy. The direct thrombin inhibitor dabigatran is, therefore, an interesting potential drug candidate. The objective of this study is to investigate whether oral administration of dabigatran etexilate in patients with a rhegmatogenous retinal detachment leads to clinical significant dabigatran levels and thrombin inhibiting activity in the vitreous and subretinal fluid.
    Evidence for comparator
    		 -
    Actual start date of recruitment
    06 Oct 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
    Netherlands: 28
    Worldwide total number of subjects
    28
    EEA total number of subjects
    28
    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)
    17
    From 65 to 84 years
    11
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 Patients with a rhegmatogenous retinal detachment, scheduled for a vitrectomy or scleral buckle surgery, were invited to participate.

    Pre-assignment
    Screening details
    		 Use of anticoagulants or medication increasing the risk of gastro-intestinal bleeding.

    Pre-assignment period milestones
    Number of subjects started
    		 28
    Number of subjects completed
    		 28

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

    Arms
    Arm title
    		 Intraocular dabigatran level.
    Arm description
    		 All patients received 220 mg dabigatran. Depending on the type of surgery either a subretinal fluid sample (n=12) or a vitreous sample (n=16) could be taken for analysis.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Dabigatran etexilate.
    Investigational medicinal product code
    EU/1/08/442
    Other name
    Pradaxa®
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Single oral dose (220 mg) administered 2 to 8 hours prior to surgery.

    Number of subjects in period 1
    		Intraocular dabigatran level.
    Started
    28
    Completed
    28

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Overall trial.
    Reporting group description
    		 -

    Reporting group values
    		 Overall trial. Total
    Number of subjects
    		 28 28
    Age categorical
    Units: Subjects
        In utero
    		 0
        Preterm newborn infants (gestational age < 37 wks)
    		 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)
    		 0
        From 65-84 years
    		 0
        85 years and over
    		 0
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 60.8 ( 7.6 ) -
    Gender categorical
    Units: Subjects
        Female
    		 6 6
        Male
    		 22 22
    Subject analysis sets

    Subject analysis set title
    Dabigatran level in the subretinal fluid.
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Dabigatran concentration in the subretinal fluid after oral administration of 220 mg dabigatran etexilate.

    Subject analysis set title
    Dabigatran level in the vitreous.
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Dabigatran concentration in the vitreous after oral administration of 220 mg dabigatran etexilate.

    Subject analysis sets values
    		 Dabigatran level in the subretinal fluid. Dabigatran level in the vitreous.
    Number of subjects
    12
    16
    Age categorical
    Units: Subjects
        In utero
        Preterm newborn infants (gestational age < 37 wks)
        Newborns (0-27 days)
        Infants and toddlers (28 days-23 months)
        Children (2-11 years)
        Adolescents (12-17 years)
        Adults (18-64 years)
        From 65-84 years
        85 years and over
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    58.2 ( 8.1 )
    62.8 ( 6.8 )
    Gender categorical
    Units: Subjects
        Female
    4
    2
        Male
    8
    14

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Intraocular dabigatran level.
    Reporting group description
    		 All patients received 220 mg dabigatran. Depending on the type of surgery either a subretinal fluid sample (n=12) or a vitreous sample (n=16) could be taken for analysis.

    Subject analysis set title
    Dabigatran level in the subretinal fluid.
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Dabigatran concentration in the subretinal fluid after oral administration of 220 mg dabigatran etexilate.

    Subject analysis set title
    Dabigatran level in the vitreous.
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Dabigatran concentration in the vitreous after oral administration of 220 mg dabigatran etexilate.

    Primary: Intraocular dabigatran level.

    		 Close Top of page
    End point title
    		 Intraocular dabigatran level.
    End point description
    End point type
    Primary
    End point timeframe
    A single dose of dabigatran etexilate (220 mg) is administered 2 to 8 hours prior to surgery.
    End point values
    		 Dabigatran level in the subretinal fluid. Dabigatran level in the vitreous.
    Number of subjects analysed
    12
    16
    Units: Concentration.
        arithmetic mean (standard deviation)
    5.8 ( 6 )
    1.8 ( 1 )
    Statistical analysis title
    		 Comparison of dabigatran levels.
    Comparison groups
    Dabigatran level in the subretinal fluid. v Dabigatran level in the vitreous.
    Number of subjects included in analysis
    28
    Analysis specification
    Post-hoc
    Analysis type
    		 superiority
    P-value
    		 < 0.05
    Method
    		 Wilcoxon (Mann-Whitney)
    Confidence interval

    Adverse events

    		 Close Top of page
    Adverse events information [1]
    Timeframe for reporting adverse events
    Postoperative period.
    Assessment type
    		 Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    10
    Reporting groups
    Reporting group title
    All participants.
    Reporting group description
    		 -

    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 non-serious adverse events were reported.
    Serious adverse events
    		 All participants.
    Total subjects affected by serious adverse events
         subjects affected / exposed
    3 / 28 (10.71%)
         number of deaths (all causes)
    0
         number of deaths resulting from adverse events
    0
    Eye disorders
    Retinal detachment (rhegmatogenous).
    Additional description: The reported SAE (i.e. a recurrent retinal detachment) is a known complication of the initial condition.
         subjects affected / exposed
    3 / 28 (10.71%)
         occurrences causally related to treatment / all
    3 / 3
         deaths causally related to treatment / all
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 0.05%
    Non-serious adverse events
    		 All participants.
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    0 / 28 (0.00%)

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? No

    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.
    This was a pilot study to demonstrate that dabigatran reaches the intraocular space.

    Online references
    http://www.ncbi.nlm.nih.gov/pubmed/28128536
    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-Tue May 07 12:10:01 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA