Clinical trial NCT02104947: Reversal of Dabigatran Anticoagulant Effect With Idarucizumab
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hemorrhage
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2014-04-07
Enrollment: 503
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility 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).

Primary outcomes:
measure: Maximum Reversal of Anticoagulant Effect of Dabigatran Based on Central Laboratory Determination of dTT or ECT
timeFrame: from the end of the first infusion up to 4 hours after the last infusion on Day 1
Secondary outcomes:
measure: Reversal of aPTT and TT From Central Laboratory
timeFrame: from the end of the first infusion up to 4 hours after the last infusion on Day 1
measure: Duration of Reversal
timeFrame: from the first infusion up to 24 hours after the last infusion on Day 1
measure: Occurrence of Major/Life-threatening/Fatal Bleeding (for Group B Only) Intraoperatively
timeFrame: within 24 hours of surgery
measure: Time to Cessation of Bleeding (for Group A Only)
timeFrame: from the first infusion up to 24 hours after the last infusion on Day 1
measure: Cmin,1 of Unbound Sum (Free) Dabigatran
timeFrame: Since the end of first vial of idarucizumab up to 4 hours after the completion of second vial
measure: 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
timeFrame: after the first vial of idarucizumab and before the start of second vial on Day1
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: Baptist Health Center for Clinical Research
state: Arkansas
city: Loma Linda
country: United States
facility: Loma Linda University Medical Center
state: California
city: Washington
country: United States
facility: MedStar Washington Hospital Center
state: District of Columbia
city: Gainesville
country: United States
facility: University of Florida College of Medicine
state: Florida
city: Jacksonville
country: United States
facility: Baptist Medical Center
state: Florida
city: Jacksonville
country: United States
facility: Mayo Clinic Cancer Center
state: Florida
city: Tampa
country: United States
facility: Tampa General Hospital
state: Florida
city: Tampa
country: United States
facility: St. Joseph's Hospital
state: Florida
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Peoria
country: United States
facility: OSF Saint Francis Medical Center
state: Illinois
city: Indianapolis
country: United States
facility: IU Health Methodist Hospital
state: Indiana
city: Munster
country: United States
facility: Community Hospital
state: Indiana
city: Baton Rouge
country: United States
facility: Our Lady of the Lake Regional Medical Center
state: Louisiana
city: Newton
country: United States
facility: Newton-Wellesley Hospital
state: Massachusetts
city: Grand Blanc
country: United States
facility: Genesys Regional Medical Center
state: Michigan
city: Jackson
country: United States
facility: Henry Ford Allegiance Health
state: Michigan
city: Saint Louis
country: United States
facility: Mercy Hospital St. Louis
state: Missouri
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Dayton
country: United States
facility: Miami Valley Hospital
state: Ohio
city: Youngstown
country: United States
facility: St. Elizabeth Youngstown Hospital
state: Ohio
city: Tulsa
country: United States
facility: St. John Health System Inc
state: Oklahoma
city: Langhorne
country: United States
facility: St. Mary Medical Center
state: Pennsylvania
city: Wynnewood
country: United States
facility: Lankenau Medical Center
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Fort Worth
country: United States
facility: Texas Health Research and Education Institute
state: Texas
city: Houston
country: United States
facility: Memorial Hermann Hospital - Texas Medical Center
state: Texas
city: Harrisonburg
country: United States
facility: Sentara RMH Medical Center
state: Virginia
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
city: Tucumán
country: Argentina
facility: Centro Privado de Cardiología
city: Concord
country: Australia
facility: Concord Repatriation General Hospital
state: New South Wales
city: Kogarah
country: Australia
facility: St George Hospital
state: New South Wales
city: St Leonards
country: Australia
facility: Royal North Shore Hospital
state: New South Wales
city: Westmead
country: Australia
facility: Westmead Hospital-Clinical Haematology Dept
state: New South Wales
city: Bedford Park
country: Australia
facility: Flinders Medical Centre
state: South Australia
city: Fitzroy
country: Australia
facility: St. Vincents Hospital (MEL)
state: Victoria
city: Linz
country: Austria
facility: KH der Barmherzigen Schwestern Linz
city: Linz
country: Austria
facility: Kepler Univ. Klinikum Linz
city: Wien
country: Austria
facility: AKH - Medical University of Vienna
city: Wien
country: Austria
facility: Wilhelminenspital
city: Aalst
country: Belgium
facility: Aalst - HOSP Onze-Lieve-Vrouw
city: Brussels
country: Belgium
facility: Brussels - UNIV St-Pierre
city: Brussel
country: Belgium
facility: Brussels - UNIV UZ Brussel
city: Bruxelles
country: Belgium
facility: Brussels - UNIV St-Luc
city: Genk
country: Belgium
facility: Genk - HOSP ZOL (St-Jan)
city: Leuven
country: Belgium
facility: UZ Leuven
city: Caxias do Sul
country: Brazil
facility: Hospital Nossa Senhora de Pompéia
city: Vancouver
country: Canada
facility: St. Paul's Hospital
state: British Columbia
city: Montreal
country: Canada
facility: Jewish General Hospital
state: Migration Data
city: Hamilton
country: Canada
facility: Hamilton General Hospital
state: Ontario
city: Hamilton
country: Canada
facility: Juravinski Hospital
state: Ontario
city: Cali
country: Colombia
facility: Fundación Valle del Lili
city: Cali
country: Colombia
facility: Centro Médico Imbanaco de Cali S.A.
city: Floridablanca
country: Colombia
facility: Fundación Cardiovascular de Colombia
city: Medellin
country: Colombia
facility: Hospital Pablo Tobón Uribe
city: Brno
country: Czechia
facility: University Hospital Brno
city: Ceske Budejovice
country: Czechia
facility: Hospital,Neurology Dept,Ceske Budejovice
city: Hradec Kralove
country: Czechia
facility: Hospital Hradec Kralove
city: Liberec
country: Czechia
facility: Regional Hospital Liberec
city: Praha 5
country: Czechia
facility: University Hospital Motol
city: Praha
country: Czechia
facility: Univ. Hospital Kralovske Vinohrady
city: Aarhus C
country: Denmark
facility: Aarhus Universitetshospital
city: Helsinki
country: Finland
facility: HUS, Kirurginen päivystysosasto P1P, Meilahti, Helsinki
city: Jyväskylä
country: Finland
facility: Keski-Suomen keskussairaala
city: Oulu
country: Finland
facility: Oulun yliopistollinen keskussairaala
city: Tampere
country: Finland
facility: TAYS, Acuta, Tampere
city: Turku
country: Finland
facility: TYKS, Akuutti sisätautihoito ASIS, Turku
city: Chambray les tours
country: France
facility: HOP Trousseau
city: Dijon
country: France
facility: HOP Bocage
city: Le Chesnay
country: France
facility: HOP André Mignot
city: Lille cedex
country: France
facility: HOP Lille, SAMU 59, Lille
city: Limoges
country: France
facility: HOP Dupuytren
city: Lyon
country: France
facility: HOP Herriot
city: Montpellier cedex
country: France
facility: HOP Lapeyronie
city: Pessac
country: France
facility: HOP Haut-Lévêque
city: Pierre Benite
country: France
facility: HOP Lyon Sud
city: Saint-Priest-en-Jarez
country: France
facility: HOP Nord
city: Toulon
country: France
facility: HOP Sainte Anne, Urgence, Toulon
city: Berlin
country: Germany
facility: Vivantes Netzwerk für Gesundheit GmbH
city: Greifswald
country: Germany
facility: Universitätsmedizin Greifswald
city: Mainz
country: Germany
facility: Universitätsmedizin der Johannes Gutenberg-Universität Mainz
city: Hong Kong
country: Hong Kong
facility: Pamela Youde Nethersole Eastern Hospital
city: Hong Kong
country: Hong Kong
facility: Prince of Wales Hospital
city: Hong Kong
country: Hong Kong
facility: Prince of Wales Hosp, Dept of Med & Therapeutics
city: Kolkatta
country: India
facility: B.M. Birla Heart research Centre
city: New Delhi
country: India
facility: Fortis Escorts Heart Institute
city: Dublin
country: Ireland
facility: St James's Hospital
city: Wilton
country: Ireland
facility: Cork University Hospital
city: Haifa
country: Israel
facility: Rambam Medical Center
city: Kfar Saba
country: Israel
facility: Meir Medical Center
city: Ramat Gan
country: Israel
facility: The Chaim Sheba Medical Center Tel Hashomer
city: Tel Aviv
country: Israel
facility: Sourasky Medical Center
city: Firenze
country: Italy
facility: Azienda Ospedaliera Careggi
city: Perugia
country: Italy
facility: Ospedale S.Maria della Misericordia, AO di Perugia
city: Reggio Emilia
country: Italy
facility: Azienda Unità Sanitaria Locale di Reggio Emilia
city: Roma
country: Italy
facility: Policlinico Gemelli
city: Roma
country: Italy
facility: Az. Osp. S.Giovanni-Addolorata
city: Aichi, Nagoya
country: Japan
facility: Japanese Red Cross Nagoya Daini Hospital
city: Ehime, Matsuyama
country: Japan
facility: Ehime Prefectural Central Hospital
city: Fukuoka, Kasuga
country: Japan
facility: Fukuoka Tokushukai Medical Center
city: Gifu, Ogaki
country: Japan
facility: Ogaki Municipal Hospital
city: Gunma, Takasaki
country: Japan
facility: National Hospital Organization Takasaki General Medical Center
city: Hyogo, Nishinomiya
country: Japan
facility: Hyogo College of Medicine Hospital
city: Kagoshima, Kagoshima
country: Japan
facility: National Hospital Organization Kagoshima Medical Center
city: Kanagawa, Kamakura
country: Japan
facility: Shonan Kamakura General Hospital
city: Osaka, Suita
country: Japan
facility: National Cerebral and Cardiovascular Center
city: Tokyo, Bunkyo-Ku
country: Japan
facility: Nippon Medical School Hospital
city: Tokyo, Tachikawa
country: Japan
facility: National Hospital Organization Disaster Medical Center
city: Yamagata, Yamagata
country: Japan
facility: Yamagata City Hospital SAISEIKAN
city: Seongnam
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
city: Seoul
country: Korea, Republic of
facility: The Catholic University of Korea, Seoul St.Mary's Hospital
city: Aguascalientes
country: Mexico
facility: Hospital Cardiologica Aguascalientes
city: Amsterdam
country: Netherlands
facility: OLVG, locatie Oosterpark
city: Amsterdam
country: Netherlands
facility: Academisch Medisch Centrum (AMC)
city: Groningen
country: Netherlands
facility: Martini Ziekenhuis
city: Maastricht
country: Netherlands
facility: Maastricht Universitair Medisch Centrum
city: Nijmegen
country: Netherlands
facility: Radboud Universitair Medisch Centrum
city: Rotterdam
country: Netherlands
facility: Erasmus Medisch Centrum
city: Christchurch
country: New Zealand
facility: Christchurch Hospital
city: Grafton / Auckland
country: New Zealand
facility: Auckland City Hospital
city: Hamilton
country: New Zealand
facility: Waikato Hospital
city: Otahuhu South Auckland
country: New Zealand
facility: Middlemore Hospital
city: Takapuna Auckland
country: New Zealand
facility: North Shore Hospital, Takapuna
city: Bergen
country: Norway
facility: Haukeland Universitetssykehus
city: Drammen
country: Norway
facility: Vestre Viken HF, Drammen Sykehus
city: Grålum
country: Norway
facility: Sykehuset Østfold Kalnes
city: Oslo
country: Norway
facility: Oslo Universitetssykehus HF, Ullevål sykehus
city: Tromsø
country: Norway
facility: Universitetssykehuset Nord-Norge, Tromsø
city: Bialystok
country: Poland
facility: Univ. Clinic Hosp, Bialystok
city: Gdansk
country: Poland
facility: University Clinical Center, Gdansk
city: Gdynia
country: Poland
facility: Saint Wincenty a Paulo Hosp., Cardiology Dept., Gdynia
city: Kielce
country: Poland
facility: Reg.Hosp Kielce,Swietokrzyskie,1.Clinic of Cardiology,Kielce
city: Krakow
country: Poland
facility: The John Paul II Hosp.,Dept.of Coronary Heart Disease,Krakow
city: Lublin
country: Poland
facility: Stefan Kardynal Wyszynski Reg.Hosp,Cardiol&IntensUnit,Lublin
city: Pulawy
country: Poland
facility: Independent Public Healthcare, Dept. of Cardiology, Pulawy
city: Warszawa
country: Poland
facility: Central Hosp.Minis.Interior,Dep.Noninvasive Cardiol,Warszawa
city: Covilhã
country: Portugal
facility: Centro Hospitalar da Cova da Beira Hospital Pêro da Covilhã
city: Lisboa
country: Portugal
facility: CHLO, EPE - Hospital S. Francisco Xavier
city: Porto
country: Portugal
facility: Centro Hospitalar do Porto, EPE
city: Porto
country: Portugal
facility: Centro Hospitalar São João,EPE
city: Saint Petersburg
country: Russian Federation
facility: City Pokrovskiy Hospital, Cardiology Dept., Saint Petersburg
city: St. Petersburg
country: Russian Federation
facility: Military Medical Academy n.a. S. M. Kirov, St. Petersburg
city: Singapore
country: Singapore
facility: National University Hospital
city: Singapore
country: Singapore
facility: Singapore General Hospital
city: Singapore
country: Singapore
facility: Changi General Hospital
city: Sandton
country: South Africa
facility: Dr. D. Adler
city: Somerset West
country: South Africa
facility: Dr. Engelbrecht
city: Alicante
country: Spain
facility: Hospital General Universitario de Alicante
city: Barcelona
country: Spain
facility: Hospital Vall d'Hebron
city: Barcelona
country: Spain
facility: Hospital Clínic de Barcelona
city: Barcelona
country: Spain
facility: Hospital de Bellvitge
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañón
city: Madrid
country: Spain
facility: Hospital Ramón y Cajal
city: Madrid
country: Spain
facility: Hospital Clínico San Carlos
city: Madrid
country: Spain
facility: Hospital La Paz
city: Malaga
country: Spain
facility: Hospital Regional Universitario de Málaga
city: Santander
country: Spain
facility: Hospital Universitario Marqués de Valdecilla
city: Valencia
country: Spain
facility: Hospital Politècnic La Fe
city: Valencia
country: Spain
facility: Hospital Clínico de Valencia
city: Vigo (Pontevedra)
country: Spain
facility: Hospital Álvaro Cunqueiro
city: Zaragoza
country: Spain
facility: Hospital Clínico Universitario Lozano Blesa
city: Göteborg
country: Sweden
facility: Sahlgrenska US, Göteborg
city: Lund
country: Sweden
facility: Skånes universitetssjukhus
city: Uppsala
country: Sweden
facility: Akademiska sjukhuset
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Medical University Chung-Ho Memorial Hospital
city: New Taipei City
country: Taiwan
facility: Far Eastern Memorial Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei
country: Taiwan
facility: Taipe Veterans General Hospital
city: Basingstoke
country: United Kingdom
facility: North Hampshire Hospital
city: Liverpool
country: United Kingdom
facility: Royal Liverpool University Hospital
city: London
country: United Kingdom
facility: Royal London Hospital
city: London
country: United Kingdom
facility: St George's Hospital
city: Oxford
country: United Kingdom
facility: Emergency Department, John Radcliffe Hospital, Oxford
city: Southampton
country: United Kingdom
facility: Southampton General Hospital
city: Taunton
country: United Kingdom
facility: Musgrove Park Hospital
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.