Reversal of Dabigatran Anticoagulant Effect With Idarucizumab

NCT02104947 | Completed Phase 3 Results

• 2 other identifiers: 1321.32013-004813-41
• Study Type: interventional
• Target: 503
• Locations: 32 countries
• Sites: 170

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.

Conditions

Hemorrhage

Outcome Measures

Primary Outcomes (1)

• Maximum Reversal of Anticoagulant Effect of Dabigatran Based on Central Laboratory Determination of dTT or ECT

  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.

  from the end of the first infusion up to 4 hours after the last infusion on Day 1

Secondary Outcomes (6)

• Reversal of aPTT and TT From Central Laboratory

  from the end of the first infusion up to 4 hours after the last infusion on Day 1

• Duration of Reversal

  from the first infusion up to 24 hours after the last infusion on Day 1

• Occurrence of Major/Life-threatening/Fatal Bleeding (for Group B Only) Intraoperatively

  within 24 hours of surgery

• Time to Cessation of Bleeding (for Group A Only)

  from the first infusion up to 24 hours after the last infusion on Day 1

• Cmin,1 of Unbound Sum (Free) Dabigatran

  Since the end of first vial of idarucizumab up to 4 hours after the completion of second vial

Study Arms (1)

idarucizumab

EXPERIMENTAL

idarucizumab Only 1 treatment, no placebo or comparator

Drug: idarucizumab

Interventions

idarucizumab DRUG

idarucizumab

idarucizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (176)

Baptist Health Center for Clinical Research

Little Rock, Arkansas, 72205, United States

Location

Loma Linda University Medical Center

Loma Linda, California, 92354, United States

Location

MedStar Washington Hospital Center

Washington D.C., District of Columbia, 20010-2975, United States

Location

University of Florida College of Medicine

Gainesville, Florida, 32610, United States

Location

Baptist Medical Center

Jacksonville, Florida, 32207, United States

Location

Mayo Clinic Cancer Center

Jacksonville, Florida, 32224, United States

Location

Tampa General Hospital

Tampa, Florida, 33606, United States

Location

St. Joseph's Hospital

Tampa, Florida, 33607, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

OSF Saint Francis Medical Center

Peoria, Illinois, 61637, United States

Location

IU Health Methodist Hospital

Indianapolis, Indiana, 46202, United States

Location

Community Hospital

Munster, Indiana, 46321, United States

Location

Our Lady of the Lake Regional Medical Center

Baton Rouge, Louisiana, 70808, United States

Location

Newton-Wellesley Hospital

Newton, Massachusetts, 02462, United States

Location

Genesys Regional Medical Center

Grand Blanc, Michigan, 48439, United States

Location

Henry Ford Allegiance Health

Jackson, Michigan, 49201, United States

Location

Mercy Hospital St. Louis

St Louis, Missouri, 63141, United States

Location

University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

University of Cincinnati

Cincinnati, Ohio, 45219, United States

Location

Miami Valley Hospital

Dayton, Ohio, 45409, United States

Location

St. Elizabeth Youngstown Hospital

Youngstown, Ohio, 44501, United States

Location

St. John Health System Inc

Tulsa, Oklahoma, 74104, United States

Location

St. Mary Medical Center

Langhorne, Pennsylvania, 19047, United States

Location

Lankenau Medical Center

Wynnewood, Pennsylvania, 19096, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Texas Health Research and Education Institute

Fort Worth, Texas, 76104, United States

Location

Memorial Hermann Hospital - Texas Medical Center

Houston, Texas, 77030, United States

Location

Sentara RMH Medical Center

Harrisonburg, Virginia, 22801, United States

Location

Virginia Commonwealth University

Richmond, Virginia, 23298-0401, United States

Location

Centro Privado de Cardiología

San Miguel de Tucumán, ZC4000, Argentina

Location

Concord Repatriation General Hospital

Concord, New South Wales, 2139, Australia

Location

St George Hospital

Kogarah, New South Wales, 2217, Australia

Location

Royal North Shore Hospital

St Leonards, New South Wales, 2065, Australia

Location

Westmead Hospital-Clinical Haematology Dept

Westmead, New South Wales, 2145, Australia

Location

Flinders Medical Centre

Bedford Park, South Australia, 5042, Australia

Location

St. Vincents Hospital (MEL)

Fitzroy, Victoria, 3065, Australia

Location

KH der Barmherzigen Schwestern Linz

Linz, 4010, Austria

Location

Kepler Univ. Klinikum Linz

Linz, 4020, Austria

Location

AKH - Medical University of Vienna

Vienna, 1090, Austria

Location

Wilhelminenspital

Vienna, 1160, Austria

Location

Aalst - HOSP Onze-Lieve-Vrouw

Aalst, 9300, Belgium

Location

Brussels - UNIV St-Pierre

Brussels, 1000, Belgium

Location

Brussels - UNIV UZ Brussel

Brussels, 1090, Belgium

Location

Brussels - UNIV St-Luc

Brussels, 1200, Belgium

Location

Genk - HOSP ZOL (St-Jan)

Genk, 3600, Belgium

Location

UZ Leuven

Leuven, 3000, Belgium

Location

Hospital Nossa Senhora de Pompéia

Caxias do Sul, 95010-005, Brazil

Location

St. Paul's Hospital

Vancouver, British Columbia, V1Y 1S1, Canada

Location

Jewish General Hospital

Montreal, Migration Data, H3T 1E2, Canada

Location

Hamilton General Hospital

Hamilton, Ontario, L8L 2X2, Canada

Location

Juravinski Hospital

Hamilton, Ontario, L8V 5C2, Canada

Location

Fundación Valle del Lili

Cali, 760032, Colombia

Location

Centro Médico Imbanaco de Cali S.A.

Cali, 760042, Colombia

Location

Fundación Cardiovascular de Colombia

Floridablanca, Colombia

Location

Hospital Pablo Tobón Uribe

Medellín, 50034, Colombia

Location

University Hospital Brno

Brno, 625 00, Czechia

Location

Hospital,Neurology Dept,Ceske Budejovice

České Budějovice, 370 01, Czechia

Location

Hospital Hradec Kralove

Hradec Králové, 500 05, Czechia

Location

Regional Hospital Liberec

Liberec, 460 63, Czechia

Location

Univ. Hospital Kralovske Vinohrady

Prague, 100 34, Czechia

Location

University Hospital Motol

Prague, 150 06, Czechia

Location

Aarhus Universitetshospital

Aarhus C, 8000, Denmark

Location

HUS, Kirurginen päivystysosasto P1P, Meilahti, Helsinki

Helsinki, 00290, Finland

Location

Keski-Suomen keskussairaala

Jyväskylä, 40620, Finland

Location

Oulun yliopistollinen keskussairaala

Oulu, 90220, Finland

Location

TAYS, Acuta, Tampere

Tampere, 33521, Finland

Location

TYKS, Akuutti sisätautihoito ASIS, Turku

Turku, 20521, Finland

Location

HOP Trousseau

Chambray-lès-Tours, 37170, France

Location

HOP Bocage

Dijon, 21079, France

Location

HOP André Mignot

Le Chesnay, 78150, France

Location

HOP Lille, SAMU 59, Lille

Lille, 59037, France

Location

HOP Dupuytren

Limoges, 87042, France

Location

HOP Herriot

Lyon, 69003, France

Location

HOP Lapeyronie

Montpellier, 34295, France

Location

HOP Haut-Lévêque

Pessac, 33604, France

Location

HOP Lyon Sud

Pierre-Bénite, 69495, France

Location

HOP Nord

Saint-Priest-en-Jarez, 42270, France

Location

HOP Sainte Anne, Urgence, Toulon

Toulon, 83041, France

Location

Vivantes Netzwerk für Gesundheit GmbH

Berlin, 12351, Germany

Location

Universitätsmedizin Greifswald

Greifswald, 17475, Germany

Location

Universitätsmedizin der Johannes Gutenberg-Universität Mainz

Mainz, 55131, Germany

Location

Pamela Youde Nethersole Eastern Hospital

Hong Kong, 0, Hong Kong

Location

Prince of Wales Hospital

Hong Kong, 0, Hong Kong

Location

Prince of Wales Hosp, Dept of Med & Therapeutics

Hong Kong, Hong Kong

Location

B.M. Birla Heart research Centre

Kolkata, 700027, India

Location

Fortis Escorts Heart Institute

New Delhi, 110025, India

Location

St James's Hospital

Dublin, DUBLIN 8, Ireland

Location

Cork University Hospital

Wilton, Ireland

Location

Rambam Medical Center

Haifa, 3109601, Israel

Location

Meir Medical Center

Kfar Saba, 44281, Israel

Location

The Chaim Sheba Medical Center Tel Hashomer

Ramat Gan, 52621, Israel

Location

Sourasky Medical Center

Tel Aviv, 64239, Israel

Location

Azienda Ospedaliera Careggi

Florence, 50134, Italy

Location

Ospedale S.Maria della Misericordia, AO di Perugia

Perugia, 06132, Italy

Location

Azienda Unità Sanitaria Locale di Reggio Emilia

Reggio Emilia, 42123, Italy

Location

Policlinico Gemelli

Roma, 00168, Italy

Location

Az. Osp. S.Giovanni-Addolorata

Roma, 00184, Italy

Location

Japanese Red Cross Nagoya Daini Hospital

Aichi, Nagoya, 466-8650, Japan

Location

Ehime Prefectural Central Hospital

Ehime, Matsuyama, 790-0024, Japan

Location

Fukuoka Tokushukai Medical Center

Fukuoka, Kasuga, 816-0864, Japan

Location

Ogaki Municipal Hospital

Gifu, Ogaki, 503-8502, Japan

Location

National Hospital Organization Takasaki General Medical Center

Gunma, Takasaki, 370-0829, Japan

Location

Hyogo College of Medicine Hospital

Hyogo, Nishinomiya, 663-8501, Japan

Location

National Hospital Organization Kagoshima Medical Center

Kagoshima, Kagoshima, 892-0853, Japan

Location

Shonan Kamakura General Hospital

Kanagawa, Kamakura, 247-8533, Japan

Location

National Cerebral and Cardiovascular Center

Osaka, Suita, 565-8565, Japan

Location

Nippon Medical School Hospital

Tokyo, Bunkyo-Ku, 113-8603, Japan

Location

National Hospital Organization Disaster Medical Center

Tokyo, Tachikawa, 190-0014, Japan

Location

Yamagata City Hospital SAISEIKAN

Yamagata, Yamagata, 990-8533, Japan

Location

Hospital Cardiologica Aguascalientes

Aguascalientes, 20297, Mexico

Location

OLVG, locatie Oosterpark

Amsterdam, 1091 AC, Netherlands

Location

Academisch Medisch Centrum (AMC)

Amsterdam, 1105 AZ, Netherlands

Location

Martini Ziekenhuis

Groningen, 9728 NT, Netherlands

Location

Maastricht Universitair Medisch Centrum

Maastricht, 6229 ER, Netherlands

Location

Radboud Universitair Medisch Centrum

Nijmegen, 6525 GA, Netherlands

Location

Erasmus Medisch Centrum

Rotterdam, 3015 CE, Netherlands

Location

Christchurch Hospital

Christchurch, 8011, New Zealand

Location

Auckland City Hospital

Grafton / Auckland, 1023, New Zealand

Location

Waikato Hospital

Hamilton, 3240, New Zealand

Location

Middlemore Hospital

Otahuhu South Auckland, 2025, New Zealand

Location

North Shore Hospital, Takapuna

Takapuna Auckland, 0620, New Zealand

Location

Haukeland Universitetssykehus

Bergen, N-5021, Norway

Location

Vestre Viken HF, Drammen Sykehus

Drammen, N-3004, Norway

Location

Sykehuset Østfold Kalnes

Grålum, N-1714, Norway

Location

Oslo Universitetssykehus HF, Ullevål sykehus

Oslo, N-0424, Norway

Location

Universitetssykehuset Nord-Norge, Tromsø

Tromsø, N-9038, Norway

Location

Univ. Clinic Hosp, Bialystok

Bialystok, 15276, Poland

Location

University Clinical Center, Gdansk

Gdansk, 80952, Poland

Location

Saint Wincenty a Paulo Hosp., Cardiology Dept., Gdynia

Gdynia, 81348, Poland

Location

Reg.Hosp Kielce,Swietokrzyskie,1.Clinic of Cardiology,Kielce

Kielce, 25736, Poland

Location

The John Paul II Hosp.,Dept.of Coronary Heart Disease,Krakow

Krakow, 31202, Poland

Location

Stefan Kardynal Wyszynski Reg.Hosp,Cardiol&IntensUnit,Lublin

Lublin, 20718, Poland

Location

Independent Public Healthcare, Dept. of Cardiology, Pulawy

Puławy, 24100, Poland

Location

Central Hosp.Minis.Interior,Dep.Noninvasive Cardiol,Warszawa

Warsaw, 02507, Poland

Location

Centro Hospitalar da Cova da Beira Hospital Pêro da Covilhã

Covilha, 6200-251, Portugal

Location

CHLO, EPE - Hospital S. Francisco Xavier

Lisbon, 1495-005, Portugal

Location

Centro Hospitalar do Porto, EPE

Porto, 4099-001, Portugal

Location

Centro Hospitalar São João,EPE

Porto, 4202-451, Portugal

Location

Military Medical Academy n.a. S. M. Kirov, St. Petersburg

Saint Petersburg, 194175, Russia

Location

City Pokrovskiy Hospital, Cardiology Dept., Saint Petersburg

Saint Petersburg, 199 106, Russia

Location

National University Hospital

Singapore, 119074, Singapore

Location

Singapore General Hospital

Singapore, 169608, Singapore

Location

Changi General Hospital

Singapore, 529889, Singapore

Location

Dr. D. Adler

Sandton, 2021, South Africa

Location

Dr. Engelbrecht

Somerset West, 7130, South Africa

Location

Seoul National University Bundang Hospital

Seongnam, 463-707, South Korea

Location

The Catholic University of Korea, Seoul St.Mary's Hospital

Seoul, 137-701, South Korea

Location

Hospital General Universitario de Alicante

Alicante, 03010, Spain

Location

Hospital Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital Clínic de Barcelona

Barcelona, 08036, Spain

Location

Hospital de Bellvitge

Barcelona, 08907, Spain

Location

Hospital General Universitario Gregorio Marañón

Madrid, 28007, Spain

Location

Hospital Ramón y Cajal

Madrid, 28034, Spain

Location

Hospital Clínico San Carlos

Madrid, 28040, Spain

Location

Hospital La Paz

Madrid, 28046, Spain

Location

Hospital Regional Universitario de Málaga

Málaga, 29010, Spain

Location

Hospital Universitario Marqués de Valdecilla

Santander, 39008, Spain

Location

Hospital Politècnic La Fe

Valencia, 46009, Spain

Location

Hospital Clínico de Valencia

Valencia, 46010, Spain

Location

Hospital Álvaro Cunqueiro

Vigo (Pontevedra), 36312, Spain

Location

Hospital Clínico Universitario Lozano Blesa

Zaragoza, 50009, Spain

Location

Sahlgrenska US, Göteborg

Gothenburg, 413 45, Sweden

Location

Skånes universitetssjukhus

Lund, 221 85, Sweden

Location

Akademiska sjukhuset

Uppsala, 751 85, Sweden

Location

Kaohsiung Medical University Chung-Ho Memorial Hospital

Kaohsiung City, 807, Taiwan

Location

Far Eastern Memorial Hospital

New Taipei City, 220, Taiwan

Location

National Taiwan University Hospital

Taipei, 100, Taiwan

Location

Taipe Veterans General Hospital

Taipei, 11217, Taiwan

Location

North Hampshire Hospital

Basingstoke, RG24 9NA, United Kingdom

Location

Royal Liverpool University Hospital

Liverpool, L7 8XP, United Kingdom

Location

Royal London Hospital

London, E1 1ES, United Kingdom

Location

St George's Hospital

London, SW17 0QT, United Kingdom

Location

Emergency Department, John Radcliffe Hospital, Oxford

Oxford, OX3 9DU, United Kingdom

Location

Southampton General Hospital

Southampton, SO16 6YD, United Kingdom

Location

Musgrove Park Hospital

Taunton, TA1 5DA, United Kingdom

Location

Related Publications (6)

• 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.

  PMID: 31582135 DERIVED

• 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.

  PMID: 31050868 DERIVED

• 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.

  PMID: 30586692 DERIVED

• 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.

  PMID: 28693366 DERIVED

• 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.

  PMID: 26095746 DERIVED

• 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.

  PMID: 26020620 DERIVED

MeSH Terms

Conditions

Hemorrhage

Interventions

idarucizumab

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Boehringer Ingelheim, Call Center
• Organization: Boehringer Ingelheim

clintriage.rdg@boehringer-ingelheim.com

1-800-243-0127

Study Officials

• Boehringer Ingelheim

  Boehringer Ingelheim

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 2, 2014
• First Posted: April 7, 2014
• Study Start: May 6, 2014
• Primary Completion: July 25, 2016
• Study Completion: October 20, 2016
• Last Updated: January 5, 2018
• Results First Posted: August 18, 2017

Record last verified: 2018-01

Locations

RU (2); BR (1); IE (2); JP (12); IN (2); AU (4); SE (3); TW (4); DE (3); CZ (6); DK (1); AR (1); GB (7); KR (2); FI (5); NL (6); IL (4); HK (3); ZA (2); CO (4); FR (11); IT (5); ME (1); NZ (5); NO (5); SG (3); BE (6); PT (4); US (30); CA (4); ES (14); PL (8)