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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02104947




Registration number
NCT02104947
Ethics application status
Date submitted
2/04/2014
Date registered
7/04/2014
Date last updated
5/01/2018

Titles & IDs
Public title
Reversal of Dabigatran Anticoagulant Effect With Idarucizumab
Scientific title
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
Secondary ID [1] 0 0
2013-004813-41
Secondary ID [2] 0 0
1321.3
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hemorrhage 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - idarucizumab

Experimental: idarucizumab - idarucizumab Only 1 treatment, no placebo or comparator


Treatment: Drugs: idarucizumab
idarucizumab
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Maximum Reversal of Anticoagulant Effect of Dabigatran Based on Central Laboratory Determination of dTT or ECT
Timepoint [1] 0 0
from the end of the first infusion up to 4 hours after the last infusion on Day 1
Secondary outcome [1] 0 0
Reversal of aPTT and TT From Central Laboratory
Timepoint [1] 0 0
from the end of the first infusion up to 4 hours after the last infusion on Day 1
Secondary outcome [2] 0 0
Duration of Reversal
Timepoint [2] 0 0
from the first infusion up to 24 hours after the last infusion on Day 1
Secondary outcome [3] 0 0
Occurrence of Major/Life-threatening/Fatal Bleeding (for Group B Only) Intraoperatively
Timepoint [3] 0 0
within 24 hours of surgery
Secondary outcome [4] 0 0
Time to Cessation of Bleeding (for Group A Only)
Timepoint [4] 0 0
from the first infusion up to 24 hours after the last infusion on Day 1
Secondary outcome [5] 0 0
Cmin,1 of Unbound Sum (Free) Dabigatran
Timepoint [5] 0 0
Since the end of first vial of idarucizumab up to 4 hours after the completion of second vial
Secondary outcome [6] 0 0
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
Timepoint [6] 0 0
after the first vial of idarucizumab and before the start of second vial on Day1

Eligibility
Key inclusion criteria
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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
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).

Study design
Purpose of the study
Treatment
Allocation to intervention
Not applicable
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
6/05/2014
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
20/10/2016
Sample size
Target
Accrual to date
Final
503
Recruitment in Australia
Recruitment state(s)
NSW,SA,VIC
Recruitment hospital [1] 0 0
Concord Repatriation General Hospital - Concord
Recruitment hospital [2] 0 0
St George Hospital - Kogarah
Recruitment hospital [3] 0 0
Royal North Shore Hospital - St Leonards
Recruitment hospital [4] 0 0
Westmead Hospital-Clinical Haematology Dept - Westmead
Recruitment hospital [5] 0 0
Flinders Medical Centre - Bedford Park
Recruitment hospital [6] 0 0
St. Vincents Hospital (MEL) - Fitzroy
Recruitment postcode(s) [1] 0 0
2139 - Concord
Recruitment postcode(s) [2] 0 0
2217 - Kogarah
Recruitment postcode(s) [3] 0 0
2065 - St Leonards
Recruitment postcode(s) [4] 0 0
2145 - Westmead
Recruitment postcode(s) [5] 0 0
5042 - Bedford Park
Recruitment postcode(s) [6] 0 0
3065 - Fitzroy
Recruitment outside Australia
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Zaragoza
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Lund
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Uppsala
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Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Boehringer Ingelheim
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT02104947
Trial related presentations / publications
Eikelboom JW, van Ryn J, Reilly P, Hylek EM, Elsaesser A, Glund S, Pollack CV, Weitz JI. Dabigatran Reversal With Idarucizumab in Patients With Renal Impairment. J Am Coll Cardiol. 2019 Oct 8;74(14):1760-1768. doi: 10.1016/j.jacc.2019.07.070.
Glund S, Coble K, Gansser D, Stangier J, Hoermann K, Pollack CV, Reilly P. Pharmacokinetics of idarucizumab and its target dabigatran in patients requiring urgent reversal of the anticoagulant effect of dabigatran. J Thromb Haemost. 2019 Aug;17(8):1319-1328. doi: 10.1111/jth.14476. Epub 2019 Jun 18.
Van der Wall SJ, Lopes RD, Aisenberg J, Reilly P, van Ryn J, Glund S, Elsaesser A, Klok FA, Pollack CV Jr, Huisman MV. Idarucizumab for Dabigatran Reversal in the Management of Patients With Gastrointestinal Bleeding. Circulation. 2019 Feb 5;139(6):748-756. doi: 10.1161/CIRCULATIONAHA.118.036710. Erratum In: Circulation. 2019 Feb 5;139(6):e36. doi: 10.1161/CIR.0000000000000660.
Pollack CV Jr, Reilly PA, van Ryn J, Eikelboom JW, Glund S, Bernstein RA, Dubiel R, Huisman MV, Hylek EM, Kam CW, Kamphuisen PW, Kreuzer J, Levy JH, Royle G, Sellke FW, Stangier J, Steiner T, Verhamme P, Wang B, Young L, Weitz JI. Idarucizumab for Dabigatran Reversal - Full Cohort Analysis. N Engl J Med. 2017 Aug 3;377(5):431-441. doi: 10.1056/NEJMoa1707278. Epub 2017 Jul 11.
Pollack CV Jr, Reilly PA, Eikelboom J, Glund S, Verhamme P, Bernstein RA, Dubiel R, Huisman MV, Hylek EM, Kamphuisen PW, Kreuzer J, Levy JH, Sellke FW, Stangier J, Steiner T, Wang B, Kam CW, Weitz JI. Idarucizumab for Dabigatran Reversal. N Engl J Med. 2015 Aug 6;373(6):511-20. doi: 10.1056/NEJMoa1502000. Epub 2015 Jun 22.
Pollack CV Jr, Reilly PA, Bernstein R, Dubiel R, Eikelboom J, Glund S, Huisman MV, Hylek E, Kam CW, Kamphuisen PW, Kreuzer J, Levy JH, Sellke F, Stangier J, Steiner T, Wang B, Weitz JI. Design and rationale for RE-VERSE AD: A phase 3 study of idarucizumab, a specific reversal agent for dabigatran. Thromb Haemost. 2015 Jul;114(1):198-205. doi: 10.1160/TH15-03-0192. Epub 2015 May 28.
Public notes

Contacts
Principal investigator
Name 0 0
Boehringer Ingelheim
Address 0 0
Boehringer Ingelheim
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT02104947