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

Hemorrhage Clinical Trial

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03343704
• Other study ID #: 1321-0019
• Status: Completed
• Phase: Phase 3
• Start date: March 26, 2018
• Est. completion date: July 2, 2020

Study information

• Verified date: May 2022
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 19
• Est. completion date: July 2, 2020
• Est. primary completion date: July 2, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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).

Related Conditions & MeSH terms

• Emergencies
• Hemorrhage

Intervention

Drug:
• Idarucizumab
Intravenous

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	From the end of first infusion up to 4 hours after the completion of the second infusion on Day 1 of the treatment period.
Primary	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.	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	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.	Up to 24 hours after the completion of the second infusion on Day 1 of the treatment period.
Secondary	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.	Up to 24 hours post-surgery.
Secondary	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.	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.
Secondary	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.	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	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.	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	Numbers of Participants With Any Adverse Events - on Treatment	Numbers of participants with any adverse events during on treatment period is reported.	Since the first infusion up until 5 days after the completion of the second infusion.
Secondary	Numbers of Participants With Any Adverse Events - Including Post Treatment Period	Numbers of participants with any adverse events until end of study is reported.	Since informed consent up to 30 days (± 7 days) after the completion of the second infusion, up to 37 days.
Secondary	Number of Participants With Serious Adverse Events - on Treatment	Number of participants with Serious adverse events during on treatment period is reported.	Since the first infusion up until 5 days after the completion of the second infusion.
Secondary	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.	Since informed consent up to 30 days (± 7 days) after the completion of the second infusion, up to 37 days.
Secondary	Number of Participants With Drug-related Adverse Events - on Treatment	Numbers of patients with drug-related adverse events during on treatment period is reported.	Since the first infusion up until 5 days after the completion of the second infusion.
Secondary	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.	Since informed consent up to 30 days (± 7 days) after the completion of the second infusion, up to 37 days.
Secondary	Number of Participants With Immune Reaction Adverse Event - on Treatment	Number of participants with immune reaction adverse event during on treatment period is reported.	Since the first infusion up until 5 days after the completion of the second infusion.
Secondary	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.	Since informed consent up to 30 days (± 7 days) after the completion of the second infusion, up to 37 days.
Secondary	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.	Since the first infusion up until 5 days after the completion of the second infusion.
Secondary	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.	Since informed consent up to 30 days (± 7 days) after the completion of the second infusion, up to 37 days.

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