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Reversal of Dabigatran Anticoagulant Effect With Idarucizumab

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ClinicalTrials.gov Identifier: NCT02104947
Recruitment Status : Completed
First Posted : April 7, 2014
Results First Posted : August 18, 2017
Last Update Posted : January 5, 2018
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim

Tracking Information
First Submitted Date  ICMJE April 2, 2014
First Posted Date  ICMJE April 7, 2014
Results First Submitted Date  ICMJE July 21, 2017
Results First Posted Date  ICMJE August 18, 2017
Last Update Posted Date January 5, 2018
Actual Study Start Date  ICMJE May 6, 2014
Actual Primary Completion Date July 25, 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 18, 2017)
Maximum Reversal of Anticoagulant Effect of Dabigatran Based on Central Laboratory Determination of dTT or ECT [ Time Frame: from the end of the first infusion up to 4 hours after the last infusion on Day 1 ]
Maximum reversal of anticoagulant effect of dabigatran based on central laboratory determination of diluted thrombin time (dTT) or ecarin clotting time (ECT), at any time point from the end of the first infusion up to 4 hours after the last infusion. Reversal is defined for patients with at least one post−dose coagulation test results and pre−dose result higher than 100% ULN (evaluable patients). Reversal is calculated as 100* (pre−dose value minus post dose value)/(pre−dose value minus 100% x ULN); if calculated reversal is > 100, it was set to 100.
Original Primary Outcome Measures  ICMJE
 (submitted: April 2, 2014)
Reversal of anticoagulant effect of dabigatran [ Time Frame: up to 4 hours ]
Change History Complete list of historical versions of study NCT02104947 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: July 21, 2017)
  • Reversal of aPTT and TT From Central Laboratory [ Time Frame: from the end of the first infusion up to 4 hours after the last infusion on Day 1 ]
    Reversal of anticoagulation as measured by Activated Partial Thromboplastin Time (aPTT) and Thrombin time (TT), at any time point since the end of first infusion up to 4 hours after the completion of the last infusion. Reversal is defined for patients with at least one post−dose coagulation test results and pre−dose result higher than 100% ULN (evaluable patients). Reversal is calculated as 100* (pre−dose value minus post dose value)/(pre−dose value minus 100% x ULN); if calculated reversal is > 100, it was set to 100.
  • Duration of Reversal [ Time Frame: from the first infusion up to 24 hours after the last infusion on Day 1 ]
    Duration of reversal, defined as the time period a patient remained completely reversed based on dTT or ECT, up to 24 hours or re-starting the treatment of dabigatran.
  • Occurrence of Major/Life-threatening/Fatal Bleeding (for Group B Only) Intraoperatively [ Time Frame: within 24 hours of surgery ]
    Occurrence of major/life-threatening/fatal bleeding (for group B only) intraoperatively and up to 24 hours post-surgery were classified according to major or life-threatening bleeding (ISTH [International Society for Thrombosis and Hemostasis] definition). 95% Confidence Interval (CI) is from Clopper-Pearson method.
  • Time to Cessation of Bleeding (for Group A Only) [ Time Frame: from the first infusion up to 24 hours after the last infusion on Day 1 ]
    Time to cessation of bleeding (for Group A only) since first infusion up to 24 hours after the completion of second infusion; bleeding status was to be categorized before and at several time points after treatment.
  • Cmin,1 of Unbound Sum (Free) Dabigatran [ Time Frame: Since the end of first vial of idarucizumab up to 4 hours after the completion of second vial ]
    Cmin,1 (Minimum concentrations at any time point since the end of first vial of idarucizumab up to 4 hours after the completion of second vial) of unbound sum (free) dabigatran, provided that two vials given not more than 15 min apart in group A and B.
  • Reversal of Anticoagulation as Measured by Diluted Thrombin Time (dTT) or Ecarin Clotting Time (ECT) After the First Vial of Idarucizumab and Before the Start of Second Vial [ Time Frame: after the first vial of idarucizumab and before the start of second vial on Day1 ]
    Reversal of anticoagulation as measured by diluted Thrombin Time (dTT) or Ecarin Clotting Time (ECT) after the first vial of idarucizumab and before the start of second vial. Reversal is defined for patients with at least one post−dose coagulation test results and pre−dose result higher than 100% ULN (evaluable patients). Reversal is calculated as 100*(pre−dose value minus post dose value)/(pre−dose value minus 100% x ULN); if calculated reversal is > 100, it was set to 100.
Original Secondary Outcome Measures  ICMJE
 (submitted: April 2, 2014)
  • Reversal of aPTT [ Time Frame: up to 4 hours ]
  • Reversal of TT [ Time Frame: up to 4 hours ]
  • Duration of Reversal [ Time Frame: up to 24 hours ]
  • Occurrence of major bleeding post-surgery (for Group B only) [ Time Frame: up to 24 hours ]
  • Time to Cessation of Bleeding (for Group A Only) [ Time Frame: up to 24 hours ]
  • Minimum unbound sum (free) dabigatran [ Time Frame: up to 4 hours ]
  • Reversal of dTT or ECT after the first infusion and before the start of the second [ Time Frame: up to 15 minutes ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Reversal of Dabigatran Anticoagulant Effect With Idarucizumab
Official Title  ICMJE A Phase III Case Series Clinical Study of the Reversal of the Anticoagulant Effects of Dabigatran by Intravenous Administration of 5.0g Idarucizumab (BI 655075) in Patients Treated Wtih Dabigatran Etexilate Who Have Uncontrolled Bleeding or Require Emergency Surgery or Procedures.RE-VERSE AD (A Study of the RE-VERSal Effects of Idarucizumab on Active Dabigatran) Trial
Brief Summary Evaluate the reversal of the anticoagulant effects of dabigatran by IV administration of 5.0g idarucizumab in patients treated with dabigatran etexilate who have uncontrolled bleeding or require emergency surgery or procedures.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Hemorrhage
Intervention  ICMJE Drug: idarucizumab
idarucizumab
Study Arms  ICMJE Experimental: idarucizumab
idarucizumab Only 1 treatment, no placebo or comparator
Intervention: Drug: idarucizumab
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: July 18, 2017)
503
Original Estimated Enrollment  ICMJE
 (submitted: April 2, 2014)
250
Actual Study Completion Date  ICMJE October 20, 2016
Actual Primary Completion Date July 25, 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion criteria:

  • Group A (Bleeding patients)

    • Overt bleeding judged by the physician to require a reversal agent
    • Currently taking dabigatran etexilate
    • At least 18 years of age
    • Written informed consent
  • Group B (Patients who are taking dabigatran who may not be bleeding, but do require an emergency surgery or procedure for a condition other than bleeding

    • Condition requiring emergency surgery or invasive procedure where adequate hemostasis is required. Emergency is defined as within the following 8 hours.
    • Current treatment with dabigatran
    • At least 18 years of age
    • Written Informed consent.

Exclusion criteria:

  • Group A (Bleeding Patients)

    • Patients with minor bleeds (epistaxis, hematuria) who can be managed with standard supportive care.
    • Patients with no clinical signs of bleeding
    • Contraindications to study medication including known hypersensitivity to the drug or its excipients.
  • Group B (Patients who require emergency surgery or procedure)

    • A surgery or procedure which is elective or where the risk of uncontrolled or unmanageable bleeding is low.
    • Contraindications to study medication including known hypersensitivity to the drug or its excipients (subjects with hereditary fructose intolerance may react to sorbitol).
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Argentina,   Australia,   Austria,   Belgium,   Brazil,   Canada,   Colombia,   Czechia,   Denmark,   Finland,   France,   Germany,   Hong Kong,   India,   Ireland,   Israel,   Italy,   Japan,   Korea, Republic of,   Mexico,   Netherlands,   New Zealand,   Norway,   Poland,   Portugal,   Russian Federation,   Singapore,   South Africa,   Spain,   Sweden,   Taiwan,   United Kingdom,   United States
Removed Location Countries Chile,   Czech Republic,   Estonia,   Latvia,   Lebanon,   Slovakia
 
Administrative Information
NCT Number  ICMJE NCT02104947
Other Study ID Numbers  ICMJE 1321.3
2013-004813-41 ( EudraCT Number )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Boehringer Ingelheim
Study Sponsor  ICMJE Boehringer Ingelheim
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
PRS Account Boehringer Ingelheim
Verification Date January 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP