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This Study Looks at the Effects of Idarucizumab in Patients Who Take Dabigatran and Need Emergency Surgery or Are Bleeding

Primary Purpose

Hemorrhage

Status
Completed
Phase
Phase 3
Locations
China
Study Type
Interventional
Intervention
Idarucizumab
Sponsored by
Boehringer Ingelheim
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hemorrhage

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion criteria:

  • ≥ 18 years at screening.
  • Male or female patients. Women of childbearing potential (WOCBP) and men able to father a child must be ready and able to use highly effective methods of birth control per ICH M3 (R2) that result in a low failure rate of less than 1% per year when used consistently and correctly. A list of contraception methods meeting these criteria is provided in the patient information.
  • Signed and dated written informed consent in accordance with ICH-GCP and local legislation prior to admission to the trial
  • Currently taking dabigatran etexilate

  • They meet the following criteria:

    • Group A: Overt bleeding judged by the physician to require a reversal agent. OR
    • Group B: A condition requiring emergency surgery or invasive procedure where adequate hemostasis is required. Emergency is defined as within the following 8 hours.

Exclusion criteria:

Group A:

  • Patients with minor bleeding (e.g. 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 (subjects with hereditary fructose intolerance may react to sorbitol).

Group B:

  • 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).

Sites / Locations

  • Beijing AnZhen Hospital
  • Peking University First Hospital
  • Cardiovascular Institute and Fu Wai Hospital
  • First Affiliated Hospital of Dalian Medical University
  • Guangdong Provincial People's Hospital
  • Sun yet-sen Memorial Hospital, Sun yet-sen Univesity
  • 2nd Affiliated Hosp Zhejiang University College of Medical
  • Zhejiang Province People's Hospital
  • The Second Affiliated Hospital to Nanchang University
  • Jiangsu Province Hospital
  • Shanghai First People's Hospital
  • The First Affiliated Hospital of Xinjiang Medical University
  • The First Affiliated Hospital of Wenzhou Med College

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Group A - patients with uncontrolled or life-threatening bleeding

Group B - patients not bleeding but requiring emergency surgery or invasive procedure

Arm Description

Outcomes

Primary Outcome Measures

Maximum Reversal of Anticoagulant Effect of Dabigatran Based on Central Laboratory Determination of Ecarin Clotting Time
Maximum reversal of anticoagulant effect of dabigatran based on central laboratory determination of ecarin clotting time is reported. The maximum reversal of anticoagulant effect of dabigatran is defined for patients with at least one post-dose coagulation test results and pre-dose result higher than 100% Upper limit of normal (ULN). Maximum reversal is calculated as 100% x (pre-dose value - post-dose value)/(pre-dose value - 100% ULN). If the calculated reversal is > 100, it was set to 100. 100% ULN is 41.26 seconds.
Maximum Reversal of Anticoagulant Effect of Dabigatran Based on Central Laboratory Determination of Diluted Thrombin Time
Maximum reversal of anticoagulant effect of dabigatran based on central laboratory determination of diluted thrombin time is reported. The maximum reversal of anticoagulant effect of dabigatran is defined for patients with at least one post-dose coagulation test results and pre-dose result higher than 100% Upper limit of normal (ULN). Maximum reversal is calculated as 100% x (pre-dose value - post-dose value)/(pre-dose value - 100% ULN). If the calculated reversal is > 100, it was set to 100. 100% ULN is 35.54 seconds.

Secondary Outcome Measures

Percentage of Participants Achieving Cessation of Bleeding Within 24 Hours After Completion of Second Infusion (for Group A Only)
Percentage of participants achieving cessation of bleeding within 24 hours after completion of second infusion for Group A is reported.
Number of Participants With Major Bleeding (for Group B Only) Intra-operatively and up to 24 Hours Post-surgery
Number of participants with major bleeding (for Group B only) intra-operatively and up to 24 hours post-surgery per International Society for Thrombosis and Hemostasis (ISTH) classification is reported.
Minimum Unbound Sum Dabigatran Concentrations Since the End of First Infusion up to 4 Hours After the Completion of the Last Infusion (Cmin,1)
Minimum unbound sum dabigatran concentrations since the end of first infusion up to 4 hours after the completion of the last infusion (Cmin,1) is reported.
Maximum Reversal of Anticoagulation as Measured by Activated Partial Thromboplastin Time (aPTT)
Maximum reversal of anticoagulation as measured by activated partial thromboplastin time (aPTT) is reported. The reversal of anticoagulant effect of dabigatran is defined for patients with at least one post-dose coagulation test results and pre-dose result higher than 100% Upper limit of normal (ULN). Maximum reversal is calculated as 100% x (pre-dose value - post-dose value)/(pre-dose value - 100% ULN). If the calculated reversal is > 100, it was set to 100. 100% ULN is 39.80 seconds.
Maximum Reversal of Anticoagulation as Measured by Thrombin Time (TT)
Maximum reversal of anticoagulation as measured by thrombin time (TT) is reported. The reversal of anticoagulant effect of dabigatran is defined for patients with at least one post-dose coagulation test results and pre-dose result higher than 100% Upper limit of normal (ULN). Maximum reversal is calculated as 100% x (pre-dose value - post-dose value)/(pre-dose value - 100% ULN). If calculated reversal is > 100, it was set to 100. 100% ULN is 14.22 seconds.
Numbers of Participants With Any Adverse Events - on Treatment
Numbers of participants with any adverse events during on treatment period is reported.
Numbers of Participants With Any Adverse Events - Including Post Treatment Period
Numbers of participants with any adverse events until end of study is reported.
Number of Participants With Serious Adverse Events - on Treatment
Number of participants with Serious adverse events during on treatment period is reported.
Number of Participants With Serious Adverse Events - Including Post Treatment Period
Number of participants with Serious adverse events until the end of study is reported.
Number of Participants With Drug-related Adverse Events - on Treatment
Numbers of patients with drug-related adverse events during on treatment period is reported.
Number of Participants With Drug-related Adverse Events - Including Post Treatment Period
Numbers of patients with drug-related adverse events until end of study is reported.
Number of Participants With Immune Reaction Adverse Event - on Treatment
Number of participants with immune reaction adverse event during on treatment period is reported.
Number of Participants With Immune Reaction Adverse Event - Including Post Treatment Period
Number of participants with immune reaction adverse event until end of study is reported.
Number of Participants With Thrombotic Events - on Treatment
Number of participants with thrombotic events (ischemic stroke, myocardial infarction, pulmonary embolism, deep vein thrombosis, systemic embolism) during on treatment period is reported.
Number of Participants With Thrombotic Events - Including Post Treatment Period
Number of participants with thrombotic events (ischemic stroke, myocardial infarction, pulmonary embolism, deep vein thrombosis, systemic embolism) until end of study is reported.

Full Information

First Posted
November 13, 2017
Last Updated
May 24, 2022
Sponsor
Boehringer Ingelheim
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1. Study Identification

Unique Protocol Identification Number
NCT03343704
Brief Title
This Study Looks at the Effects of Idarucizumab in Patients Who Take Dabigatran and Need Emergency Surgery or Are Bleeding
Official Title
A Phase III, Case Series Clinical Study of the Reversal of the Anticoagulant Effects of Dabigatran by Intravenous Administration of Idarucizumab (BI 655075) in Patients Treated With Dabigatran Etexilate Who Have Uncontrolled Bleeding or Require Emergency Surgery or Procedures.
Study Type
Interventional

2. Study Status

Record Verification Date
May 2022
Overall Recruitment Status
Completed
Study Start Date
March 26, 2018 (Actual)
Primary Completion Date
July 2, 2020 (Actual)
Study Completion Date
July 2, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Boehringer Ingelheim

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
The primary objective is to demonstrate reversal of the anticoagulant effect of dabigatran in patients treated with dabigatran etexilate who have uncontrolled or life-threatening bleeding requiring urgent intervention, and in patients treated with dabigatran etexilate who require emergency surgery or other invasive procedure. The secondary objectives are to assess the reduction or cessation of bleeding, evaluate the clinical outcomes, safety and the pharmacokinetics of dabigatran in the presence of idarucizumab.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hemorrhage

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
19 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Group A - patients with uncontrolled or life-threatening bleeding
Arm Type
Experimental
Arm Title
Group B - patients not bleeding but requiring emergency surgery or invasive procedure
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Idarucizumab
Other Intervention Name(s)
PRAXBIND, Praxbind, Prizbind
Intervention Description
Intravenous
Primary Outcome Measure Information:
Title
Maximum Reversal of Anticoagulant Effect of Dabigatran Based on Central Laboratory Determination of Ecarin Clotting Time
Description
Maximum reversal of anticoagulant effect of dabigatran based on central laboratory determination of ecarin clotting time is reported. The maximum reversal of anticoagulant effect of dabigatran is defined for patients with at least one post-dose coagulation test results and pre-dose result higher than 100% Upper limit of normal (ULN). Maximum reversal is calculated as 100% x (pre-dose value - post-dose value)/(pre-dose value - 100% ULN). If the calculated reversal is > 100, it was set to 100. 100% ULN is 41.26 seconds.
Time Frame
From the end of first infusion up to 4 hours after the completion of the second infusion on Day 1 of the treatment period.
Title
Maximum Reversal of Anticoagulant Effect of Dabigatran Based on Central Laboratory Determination of Diluted Thrombin Time
Description
Maximum reversal of anticoagulant effect of dabigatran based on central laboratory determination of diluted thrombin time is reported. The maximum reversal of anticoagulant effect of dabigatran is defined for patients with at least one post-dose coagulation test results and pre-dose result higher than 100% Upper limit of normal (ULN). Maximum reversal is calculated as 100% x (pre-dose value - post-dose value)/(pre-dose value - 100% ULN). If the calculated reversal is > 100, it was set to 100. 100% ULN is 35.54 seconds.
Time Frame
From the end of first infusion up to 4 hours after the completion of the second infusion on Day 1 of the treatment period.
Secondary Outcome Measure Information:
Title
Percentage of Participants Achieving Cessation of Bleeding Within 24 Hours After Completion of Second Infusion (for Group A Only)
Description
Percentage of participants achieving cessation of bleeding within 24 hours after completion of second infusion for Group A is reported.
Time Frame
Up to 24 hours after the completion of the second infusion on Day 1 of the treatment period.
Title
Number of Participants With Major Bleeding (for Group B Only) Intra-operatively and up to 24 Hours Post-surgery
Description
Number of participants with major bleeding (for Group B only) intra-operatively and up to 24 hours post-surgery per International Society for Thrombosis and Hemostasis (ISTH) classification is reported.
Time Frame
Up to 24 hours post-surgery.
Title
Minimum Unbound Sum Dabigatran Concentrations Since the End of First Infusion up to 4 Hours After the Completion of the Last Infusion (Cmin,1)
Description
Minimum unbound sum dabigatran concentrations since the end of first infusion up to 4 hours after the completion of the last infusion (Cmin,1) is reported.
Time Frame
Just prior to the second infusion (last infusion) and 10 minutes (min), 30 min, 1 hour (h), 2 h, and 4 h after the end of the second infusion.
Title
Maximum Reversal of Anticoagulation as Measured by Activated Partial Thromboplastin Time (aPTT)
Description
Maximum reversal of anticoagulation as measured by activated partial thromboplastin time (aPTT) is reported. The reversal of anticoagulant effect of dabigatran is defined for patients with at least one post-dose coagulation test results and pre-dose result higher than 100% Upper limit of normal (ULN). Maximum reversal is calculated as 100% x (pre-dose value - post-dose value)/(pre-dose value - 100% ULN). If the calculated reversal is > 100, it was set to 100. 100% ULN is 39.80 seconds.
Time Frame
From the end of first infusion up to 4 hours after the completion of the second infusion on Day 1 of the treatment period.
Title
Maximum Reversal of Anticoagulation as Measured by Thrombin Time (TT)
Description
Maximum reversal of anticoagulation as measured by thrombin time (TT) is reported. The reversal of anticoagulant effect of dabigatran is defined for patients with at least one post-dose coagulation test results and pre-dose result higher than 100% Upper limit of normal (ULN). Maximum reversal is calculated as 100% x (pre-dose value - post-dose value)/(pre-dose value - 100% ULN). If calculated reversal is > 100, it was set to 100. 100% ULN is 14.22 seconds.
Time Frame
From the end of first infusion up to 4 hours after the completion of the second infusion on Day 1 of the treatment period.
Title
Numbers of Participants With Any Adverse Events - on Treatment
Description
Numbers of participants with any adverse events during on treatment period is reported.
Time Frame
Since the first infusion up until 5 days after the completion of the second infusion.
Title
Numbers of Participants With Any Adverse Events - Including Post Treatment Period
Description
Numbers of participants with any adverse events until end of study is reported.
Time Frame
Since informed consent up to 30 days (± 7 days) after the completion of the second infusion, up to 37 days.
Title
Number of Participants With Serious Adverse Events - on Treatment
Description
Number of participants with Serious adverse events during on treatment period is reported.
Time Frame
Since the first infusion up until 5 days after the completion of the second infusion.
Title
Number of Participants With Serious Adverse Events - Including Post Treatment Period
Description
Number of participants with Serious adverse events until the end of study is reported.
Time Frame
Since informed consent up to 30 days (± 7 days) after the completion of the second infusion, up to 37 days.
Title
Number of Participants With Drug-related Adverse Events - on Treatment
Description
Numbers of patients with drug-related adverse events during on treatment period is reported.
Time Frame
Since the first infusion up until 5 days after the completion of the second infusion.
Title
Number of Participants With Drug-related Adverse Events - Including Post Treatment Period
Description
Numbers of patients with drug-related adverse events until end of study is reported.
Time Frame
Since informed consent up to 30 days (± 7 days) after the completion of the second infusion, up to 37 days.
Title
Number of Participants With Immune Reaction Adverse Event - on Treatment
Description
Number of participants with immune reaction adverse event during on treatment period is reported.
Time Frame
Since the first infusion up until 5 days after the completion of the second infusion.
Title
Number of Participants With Immune Reaction Adverse Event - Including Post Treatment Period
Description
Number of participants with immune reaction adverse event until end of study is reported.
Time Frame
Since informed consent up to 30 days (± 7 days) after the completion of the second infusion, up to 37 days.
Title
Number of Participants With Thrombotic Events - on Treatment
Description
Number of participants with thrombotic events (ischemic stroke, myocardial infarction, pulmonary embolism, deep vein thrombosis, systemic embolism) during on treatment period is reported.
Time Frame
Since the first infusion up until 5 days after the completion of the second infusion.
Title
Number of Participants With Thrombotic Events - Including Post Treatment Period
Description
Number of participants with thrombotic events (ischemic stroke, myocardial infarction, pulmonary embolism, deep vein thrombosis, systemic embolism) until end of study is reported.
Time Frame
Since informed consent up to 30 days (± 7 days) after the completion of the second infusion, up to 37 days.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion criteria: ≥ 18 years at screening. Male or female patients. Women of childbearing potential (WOCBP) and men able to father a child must be ready and able to use highly effective methods of birth control per ICH M3 (R2) that result in a low failure rate of less than 1% per year when used consistently and correctly. A list of contraception methods meeting these criteria is provided in the patient information. Signed and dated written informed consent in accordance with ICH-GCP and local legislation prior to admission to the trial Currently taking dabigatran etexilate They meet the following criteria: Group A: Overt bleeding judged by the physician to require a reversal agent. OR Group B: A condition requiring emergency surgery or invasive procedure where adequate hemostasis is required. Emergency is defined as within the following 8 hours. Exclusion criteria: Group A: Patients with minor bleeding (e.g. 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 (subjects with hereditary fructose intolerance may react to sorbitol). Group B: 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).
Facility Information:
Facility Name
Beijing AnZhen Hospital
City
Beijing
ZIP/Postal Code
100029
Country
China
Facility Name
Peking University First Hospital
City
Beijing
ZIP/Postal Code
100034
Country
China
Facility Name
Cardiovascular Institute and Fu Wai Hospital
City
Beijing
ZIP/Postal Code
100037
Country
China
Facility Name
First Affiliated Hospital of Dalian Medical University
City
Dalian
ZIP/Postal Code
116011
Country
China
Facility Name
Guangdong Provincial People's Hospital
City
Guangzhou
ZIP/Postal Code
510080
Country
China
Facility Name
Sun yet-sen Memorial Hospital, Sun yet-sen Univesity
City
Guangzhou
ZIP/Postal Code
510288
Country
China
Facility Name
2nd Affiliated Hosp Zhejiang University College of Medical
City
Hangzhou
ZIP/Postal Code
310009
Country
China
Facility Name
Zhejiang Province People's Hospital
City
Hangzhou
ZIP/Postal Code
310014
Country
China
Facility Name
The Second Affiliated Hospital to Nanchang University
City
Nanchang
ZIP/Postal Code
330006
Country
China
Facility Name
Jiangsu Province Hospital
City
Nanjing, Jiangsu Province
ZIP/Postal Code
210029
Country
China
Facility Name
Shanghai First People's Hospital
City
Shanghai
ZIP/Postal Code
200080
Country
China
Facility Name
The First Affiliated Hospital of Xinjiang Medical University
City
Urumqi
ZIP/Postal Code
830054
Country
China
Facility Name
The First Affiliated Hospital of Wenzhou Med College
City
Wenzhou
ZIP/Postal Code
325000
Country
China

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Once the criteria in section "Time Frame" are fulfilled, researchers can use the following link https://www.mystudywindow.com/msw/datasharing to request access to the clinical study documents regarding this study, and upon a signed "Document Sharing Agreement". Furthermore, researchers can request access to the clinical study data, for this and other listed studies, after the submission of a research proposal and according to the terms outlined in the website.
IPD Sharing Time Frame
After structured results have been posted, all regulatory activities are completed in the US and EU for the product and indication, and after the primary manuscript has been accepted for publication.
IPD Sharing Access Criteria
For study documents - upon signing of a 'Document Sharing Agreement'. For study data - 1. after the submission and approval of the research proposal (checks will be performed by the sponsor and/or the independent review panel, including checking that the planned analysis does not compete with sponsor's publication plan); 2. and upon signing of a legal agreement.
IPD Sharing URL
https://www.mystudywindow.com/msw/datasharing
Links:
URL
http://www.mystudywindow.com/
Description
Related Info

Learn more about this trial

This Study Looks at the Effects of Idarucizumab in Patients Who Take Dabigatran and Need Emergency Surgery or Are Bleeding

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