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Reversal of Dabigatran Anticoagulant Effect With Idarucizumab

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT02104947
First Posted: April 7, 2014
Last Update Posted: October 3, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Boehringer Ingelheim
  Purpose
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.

Condition Intervention Phase
Hemorrhage Drug: idarucizumab Phase 3

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official 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

Resource links provided by NLM:


Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • 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.



Secondary Outcome Measures:
  • 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.



Enrollment: 503
Actual Study Start Date: May 6, 2014
Study Completion Date: October 20, 2016
Primary Completion Date: July 25, 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: idarucizumab
idarucizumab Only 1 treatment, no placebo or comparator
Drug: idarucizumab
idarucizumab

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

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).
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02104947


  Hide Study Locations
Locations
United States, Arkansas
Little Rock, Arkansas, United States
United States, California
Loma Linda, California, United States
United States, District of Columbia
Washington, D.C., District of Columbia, United States
United States, Florida
Gainesville, Florida, United States
Jacksonville, Florida, United States
Tampa, Florida, United States
United States, Illinois
Chicago, Illinois, United States
Peoria, Illinois, United States
United States, Indiana
Indianapolis, Indiana, United States
Munster, Indiana, United States
United States, Massachusetts
Newton, Massachusetts, United States
United States, Michigan
Grand Blanc, Michigan, United States
Jackson, Michigan, United States
United States, Missouri
Saint Louis, Missouri, United States
United States, Nebraska
Omaha, Nebraska, United States
United States, Ohio
Cincinnati, Ohio, United States
Dayton, Ohio, United States
Youngstown, Ohio, United States
United States, Oklahoma
Tulsa, Oklahoma, United States
United States, Pennsylvania
Langhorne, Pennsylvania, United States
Wynnewood, Pennsylvania, United States
United States, South Carolina
Charleston, South Carolina, United States
United States, Texas
Fort Worth, Texas, United States
Argentina
Tucumán, Argentina
Australia, New South Wales
Concord, New South Wales, Australia
Kogarah, New South Wales, Australia
St Leonards, New South Wales, Australia
Westmead, New South Wales, Australia
Australia, Victoria
Fitzroy, Victoria, Australia
Austria
Linz, Austria
Wien, Austria
Belgium
Brussels, Belgium
Brussel, Belgium
Bruxelles, Belgium
Genk, Belgium
Leuven, Belgium
Brazil
Caxias do Sul, Brazil
Canada, British Columbia
Vancouver, British Columbia, Canada
Canada, Migration Data
Montreal, Migration Data, Canada
Canada, Ontario
Hamilton, Ontario, Canada
Colombia
Cali, Colombia
Floridablanca, Colombia
Medellin, Colombia
Czechia
Brno, Czechia
Ceske Budejovice, Czechia
Hradec Kralove, Czechia
Liberec, Czechia
Praha 5, Czechia
Praha, Czechia
Denmark
Aarhus C, Denmark
Finland
Helsinki, Finland
Jyväskylä, Finland
Oulu, Finland
Tampere, Finland
Turku, Finland
France
Chambray les tours, France
Dijon, France
Le Chesnay, France
Lille cedex, France
Limoges cedex, France
Lyon, France
Montpellier cedex, France
Pessac, France
Saint-Priest-en-Jarez, France
Toulon, France
Germany
Berlin, Germany
Greifswald, Germany
Mainz, Germany
Hong Kong
Hong Kong, Hong Kong
India
Kolkatta, India
Ireland
Wilton, Ireland
Israel
Haifa, Israel
Kfar Saba, Israel
Ramat Gan, Israel
Tel Aviv, Israel
Italy
Firenze, Italy
Perugia, Italy
Reggio Emilia, Italy
Roma, Italy
Japan
Aichi, Nagoya, Japan
Ehime, Matsuyama-shi, Japan
Fukuoka, Kasuga-shi, Japan
Gunma, Takasaki-shi, Japan
Hokkaido, Sapporo, Japan
Hyogo, Nishinomiya-shi, Japan
Kagoshima, Kagoshima-shi, Japan
Kanagawa, Kamakura, Japan
Osaka, Suita, Japan
Tokyo, Bunkyo-Ku, Japan
Tokyo,Tachikawa, Japan
Yamagata, Yamagata, Japan
Korea, Republic of
Daegu, Korea, Republic of
Goyang, Korea, Republic of
Gwangju, Korea, Republic of
Pusan, Korea, Republic of
Seongnam, Korea, Republic of
Seoul, Korea, Republic of
Mexico
Aguascalientes, Mexico
Netherlands
Amsterdam, Netherlands
Groningen, Netherlands
Maastricht, Netherlands
Nijmegen, Netherlands
New Zealand
Christchurch, New Zealand
Grafton / Auckland, New Zealand
Hamilton, New Zealand
Otahuhu South Auckland, New Zealand
Takapuna Auckland, New Zealand
Norway
Bergen, Norway
Drammen, Norway
Oslo, Norway
Poland
Bialystok, Poland
Gdansk, Poland
Gdynia, Poland
Kielce, Poland
Krakow, Poland
Lublin, Poland
Pulawy, Poland
Warszawa, Poland
Portugal
Covilhã, Portugal
Porto, Portugal
Russian Federation
Saint Petersburg, Russian Federation
St. Petersburg, Russian Federation
Singapore
Singapore, Singapore
South Africa
Panorama, South Africa
Sandton, South Africa
Somerset West, South Africa
Spain
Alicante, Spain
Barcelona, Spain
Madrid, Spain
Santander, Spain
Valencia, Spain
Vigo (Pontevedra), Spain
Zaragoza, Spain
Sweden
Lund, Sweden
Taiwan
Kaohsiung, Taiwan
New Taipei City, Taiwan
Taipei, Taiwan
United Kingdom
Basingstoke, United Kingdom
London, United Kingdom
Oxford, United Kingdom
Sponsors and Collaborators
Boehringer Ingelheim
Investigators
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
  More Information

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT02104947     History of Changes
Other Study ID Numbers: 1321.3
2013-004813-41 ( EudraCT Number: EudraCT )
First Submitted: April 2, 2014
First Posted: April 7, 2014
Results First Submitted: July 21, 2017
Results First Posted: August 18, 2017
Last Update Posted: October 3, 2017
Last Verified: September 2017

Additional relevant MeSH terms:
Hemorrhage
Pathologic Processes
Dabigatran
Anticoagulants
Antithrombins
Serine Proteinase Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action