Trial Review

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 endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/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
N/A
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
Country [1] 0 0
United States of America
State/province [1] 0 0
Arkansas
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
District of Columbia
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Illinois
Country [6] 0 0
United States of America
State/province [6] 0 0
Indiana
Country [7] 0 0
United States of America
State/province [7] 0 0
Louisiana
Country [8] 0 0
United States of America
State/province [8] 0 0
Massachusetts
Country [9] 0 0
United States of America
State/province [9] 0 0
Michigan
Country [10] 0 0
United States of America
State/province [10] 0 0
Missouri
Country [11] 0 0
United States of America
State/province [11] 0 0
Nebraska
Country [12] 0 0
United States of America
State/province [12] 0 0
North Carolina
Country [13] 0 0
United States of America
State/province [13] 0 0
Ohio
Country [14] 0 0
United States of America
State/province [14] 0 0
Oklahoma
Country [15] 0 0
United States of America
State/province [15] 0 0
Pennsylvania
Country [16] 0 0
United States of America
State/province [16] 0 0
South Carolina
Country [17] 0 0
United States of America
State/province [17] 0 0
Texas
Country [18] 0 0
United States of America
State/province [18] 0 0
Virginia
Country [19] 0 0
Argentina
State/province [19] 0 0
Tucumán
Country [20] 0 0
Austria
State/province [20] 0 0
Linz
Country [21] 0 0
Austria
State/province [21] 0 0
Wien
Country [22] 0 0
Belgium
State/province [22] 0 0
Aalst
Country [23] 0 0
Belgium
State/province [23] 0 0
Brussels
Country [24] 0 0
Belgium
State/province [24] 0 0
Brussel
Country [25] 0 0
Belgium
State/province [25] 0 0
Bruxelles
Country [26] 0 0
Belgium
State/province [26] 0 0
Genk
Country [27] 0 0
Belgium
State/province [27] 0 0
Leuven
Country [28] 0 0
Brazil
State/province [28] 0 0
Caxias do Sul
Country [29] 0 0
Canada
State/province [29] 0 0
British Columbia
Country [30] 0 0
Canada
State/province [30] 0 0
Migration Data
Country [31] 0 0
Canada
State/province [31] 0 0
Ontario
Country [32] 0 0
Colombia
State/province [32] 0 0
Cali
Country [33] 0 0
Colombia
State/province [33] 0 0
Floridablanca
Country [34] 0 0
Colombia
State/province [34] 0 0
Medellin
Country [35] 0 0
Czechia
State/province [35] 0 0
Brno
Country [36] 0 0
Czechia
State/province [36] 0 0
Ceske Budejovice
Country [37] 0 0
Czechia
State/province [37] 0 0
Hradec Kralove
Country [38] 0 0
Czechia
State/province [38] 0 0
Liberec
Country [39] 0 0
Czechia
State/province [39] 0 0
Praha 5
Country [40] 0 0
Czechia
State/province [40] 0 0
Praha
Country [41] 0 0
Denmark
State/province [41] 0 0
Aarhus C
Country [42] 0 0
Finland
State/province [42] 0 0
Helsinki
Country [43] 0 0
Finland
State/province [43] 0 0
Jyväskylä
Country [44] 0 0
Finland
State/province [44] 0 0
Oulu
Country [45] 0 0
Finland
State/province [45] 0 0
Tampere
Country [46] 0 0
Finland
State/province [46] 0 0
Turku
Country [47] 0 0
France
State/province [47] 0 0
Chambray les tours
Country [48] 0 0
France
State/province [48] 0 0
Dijon
Country [49] 0 0
France
State/province [49] 0 0
Le Chesnay
Country [50] 0 0
France
State/province [50] 0 0
Lille cedex
Country [51] 0 0
France
State/province [51] 0 0
Limoges
Country [52] 0 0
France
State/province [52] 0 0
Lyon
Country [53] 0 0
France
State/province [53] 0 0
Montpellier cedex
Country [54] 0 0
France
State/province [54] 0 0
Pessac
Country [55] 0 0
France
State/province [55] 0 0
Pierre Benite
Country [56] 0 0
France
State/province [56] 0 0
Saint-Priest-en-Jarez
Country [57] 0 0
France
State/province [57] 0 0
Toulon
Country [58] 0 0
Germany
State/province [58] 0 0
Berlin
Country [59] 0 0
Germany
State/province [59] 0 0
Greifswald
Country [60] 0 0
Germany
State/province [60] 0 0
Mainz
Country [61] 0 0
Hong Kong
State/province [61] 0 0
Hong Kong
Country [62] 0 0
India
State/province [62] 0 0
Kolkatta
Country [63] 0 0
India
State/province [63] 0 0
New Delhi
Country [64] 0 0
Ireland
State/province [64] 0 0
Dublin
Country [65] 0 0
Ireland
State/province [65] 0 0
Wilton
Country [66] 0 0
Israel
State/province [66] 0 0
Haifa
Country [67] 0 0
Israel
State/province [67] 0 0
Kfar Saba
Country [68] 0 0
Israel
State/province [68] 0 0
Ramat Gan
Country [69] 0 0
Israel
State/province [69] 0 0
Tel Aviv
Country [70] 0 0
Italy
State/province [70] 0 0
Firenze
Country [71] 0 0
Italy
State/province [71] 0 0
Perugia
Country [72] 0 0
Italy
State/province [72] 0 0
Reggio Emilia
Country [73] 0 0
Italy
State/province [73] 0 0
Roma
Country [74] 0 0
Japan
State/province [74] 0 0
Aichi, Nagoya
Country [75] 0 0
Japan
State/province [75] 0 0
Ehime, Matsuyama
Country [76] 0 0
Japan
State/province [76] 0 0
Fukuoka, Kasuga
Country [77] 0 0
Japan
State/province [77] 0 0
Gifu, Ogaki
Country [78] 0 0
Japan
State/province [78] 0 0
Gunma, Takasaki
Country [79] 0 0
Japan
State/province [79] 0 0
Hyogo, Nishinomiya
Country [80] 0 0
Japan
State/province [80] 0 0
Kagoshima, Kagoshima
Country [81] 0 0
Japan
State/province [81] 0 0
Kanagawa, Kamakura
Country [82] 0 0
Japan
State/province [82] 0 0
Osaka, Suita
Country [83] 0 0
Japan
State/province [83] 0 0
Tokyo, Bunkyo-Ku
Country [84] 0 0
Japan
State/province [84] 0 0
Tokyo, Tachikawa
Country [85] 0 0
Japan
State/province [85] 0 0
Yamagata, Yamagata
Country [86] 0 0
Korea, Republic of
State/province [86] 0 0
Seongnam
Country [87] 0 0
Korea, Republic of
State/province [87] 0 0
Seoul
Country [88] 0 0
Mexico
State/province [88] 0 0
Aguascalientes
Country [89] 0 0
Netherlands
State/province [89] 0 0
Amsterdam
Country [90] 0 0
Netherlands
State/province [90] 0 0
Groningen
Country [91] 0 0
Netherlands
State/province [91] 0 0
Maastricht
Country [92] 0 0
Netherlands
State/province [92] 0 0
Nijmegen
Country [93] 0 0
Netherlands
State/province [93] 0 0
Rotterdam
Country [94] 0 0
New Zealand
State/province [94] 0 0
Christchurch
Country [95] 0 0
New Zealand
State/province [95] 0 0
Grafton / Auckland
Country [96] 0 0
New Zealand
State/province [96] 0 0
Hamilton
Country [97] 0 0
New Zealand
State/province [97] 0 0
Otahuhu South Auckland
Country [98] 0 0
New Zealand
State/province [98] 0 0
Takapuna Auckland
Country [99] 0 0
Norway
State/province [99] 0 0
Bergen
Country [100] 0 0
Norway
State/province [100] 0 0
Drammen
Country [101] 0 0
Norway
State/province [101] 0 0
Grålum
Country [102] 0 0
Norway
State/province [102] 0 0
Oslo
Country [103] 0 0
Norway
State/province [103] 0 0
Tromsø
Country [104] 0 0
Poland
State/province [104] 0 0
Bialystok
Country [105] 0 0
Poland
State/province [105] 0 0
Gdansk
Country [106] 0 0
Poland
State/province [106] 0 0
Gdynia
Country [107] 0 0
Poland
State/province [107] 0 0
Kielce
Country [108] 0 0
Poland
State/province [108] 0 0
Krakow
Country [109] 0 0
Poland
State/province [109] 0 0
Lublin
Country [110] 0 0
Poland
State/province [110] 0 0
Pulawy
Country [111] 0 0
Poland
State/province [111] 0 0
Warszawa
Country [112] 0 0
Portugal
State/province [112] 0 0
Covilhã
Country [113] 0 0
Portugal
State/province [113] 0 0
Lisboa
Country [114] 0 0
Portugal
State/province [114] 0 0
Porto
Country [115] 0 0
Russian Federation
State/province [115] 0 0
Saint Petersburg
Country [116] 0 0
Russian Federation
State/province [116] 0 0
St. Petersburg
Country [117] 0 0
Singapore
State/province [117] 0 0
Singapore
Country [118] 0 0
South Africa
State/province [118] 0 0
Sandton
Country [119] 0 0
South Africa
State/province [119] 0 0
Somerset West
Country [120] 0 0
Spain
State/province [120] 0 0
Alicante
Country [121] 0 0
Spain
State/province [121] 0 0
Barcelona
Country [122] 0 0
Spain
State/province [122] 0 0
Madrid
Country [123] 0 0
Spain
State/province [123] 0 0
Malaga
Country [124] 0 0
Spain
State/province [124] 0 0
Santander
Country [125] 0 0
Spain
State/province [125] 0 0
Valencia
Country [126] 0 0
Spain
State/province [126] 0 0
Vigo (Pontevedra)
Country [127] 0 0
Spain
State/province [127] 0 0
Zaragoza
Country [128] 0 0
Sweden
State/province [128] 0 0
Göteborg
Country [129] 0 0
Sweden
State/province [129] 0 0
Lund
Country [130] 0 0
Sweden
State/province [130] 0 0
Uppsala
Country [131] 0 0
Taiwan
State/province [131] 0 0
Kaohsiung
Country [132] 0 0
Taiwan
State/province [132] 0 0
New Taipei City
Country [133] 0 0
Taiwan
State/province [133] 0 0
Taipei
Country [134] 0 0
United Kingdom
State/province [134] 0 0
Basingstoke
Country [135] 0 0
United Kingdom
State/province [135] 0 0
Liverpool
Country [136] 0 0
United Kingdom
State/province [136] 0 0
London
Country [137] 0 0
United Kingdom
State/province [137] 0 0
Oxford
Country [138] 0 0
United Kingdom
State/province [138] 0 0
Southampton
Country [139] 0 0
United Kingdom
State/province [139] 0 0
Taunton

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/ct2/show/NCT02104947
Trial related presentations / publications
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/ct2/show/NCT02104947