Clinical trial NCT03343704: 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
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hemorrhage
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2017-11-17
Enrollment: 19
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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).

Primary outcomes:
measure: Maximum Reversal of Anticoagulant Effect of Dabigatran Based on Central Laboratory Determination of Ecarin Clotting Time
timeFrame: From the end of first infusion up to 4 hours after the completion of the second infusion on Day 1 of the treatment period.
measure: Maximum Reversal of Anticoagulant Effect of Dabigatran Based on Central Laboratory Determination of Diluted Thrombin Time
timeFrame: 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 outcomes:
measure: Percentage of Participants Achieving Cessation of Bleeding Within 24 Hours After Completion of Second Infusion (for Group A Only)
timeFrame: Up to 24 hours after the completion of the second infusion on Day 1 of the treatment period.
measure: Number of Participants With Major Bleeding (for Group B Only) Intra-operatively and up to 24 Hours Post-surgery
timeFrame: Up to 24 hours post-surgery.
measure: Minimum Unbound Sum Dabigatran Concentrations Since the End of First Infusion up to 4 Hours After the Completion of the Last Infusion (Cmin,1)
timeFrame: 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.
measure: Maximum Reversal of Anticoagulation as Measured by Activated Partial Thromboplastin Time (aPTT)
timeFrame: From the end of first infusion up to 4 hours after the completion of the second infusion on Day 1 of the treatment period.
measure: Maximum Reversal of Anticoagulation as Measured by Thrombin Time (TT)
timeFrame: From the end of first infusion up to 4 hours after the completion of the second infusion on Day 1 of the treatment period.
measure: Numbers of Participants With Any Adverse Events - on Treatment
timeFrame: Since the first infusion up until 5 days after the completion of the second infusion.
measure: Numbers of Participants With Any Adverse Events - Including Post Treatment Period
timeFrame: Since informed consent up to 30 days (± 7 days) after the completion of the second infusion, up to 37 days.
measure: Number of Participants With Serious Adverse Events - on Treatment
timeFrame: Since the first infusion up until 5 days after the completion of the second infusion.
measure: Number of Participants With Serious Adverse Events - Including Post Treatment Period
timeFrame: Since informed consent up to 30 days (± 7 days) after the completion of the second infusion, up to 37 days.
measure: Number of Participants With Drug-related Adverse Events - on Treatment
timeFrame: Since the first infusion up until 5 days after the completion of the second infusion.
measure: Number of Participants With Drug-related Adverse Events - Including Post Treatment Period
timeFrame: Since informed consent up to 30 days (± 7 days) after the completion of the second infusion, up to 37 days.
measure: Number of Participants With Immune Reaction Adverse Event - on Treatment
timeFrame: Since the first infusion up until 5 days after the completion of the second infusion.
measure: Number of Participants With Immune Reaction Adverse Event - Including Post Treatment Period
timeFrame: Since informed consent up to 30 days (± 7 days) after the completion of the second infusion, up to 37 days.
measure: Number of Participants With Thrombotic Events - on Treatment
timeFrame: Since the first infusion up until 5 days after the completion of the second infusion.
measure: Number of Participants With Thrombotic Events - Including Post Treatment Period
timeFrame: Since informed consent up to 30 days (± 7 days) after the completion of the second infusion, up to 37 days.
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing AnZhen Hospital
city: Beijing
country: China
facility: Peking University First Hospital
city: Beijing
country: China
facility: Cardiovascular Institute and Fu Wai Hospital
city: Dalian
country: China
facility: First Affiliated Hospital of Dalian Medical University
city: Guangzhou
country: China
facility: Guangdong Provincial People's Hospital
city: Guangzhou
country: China
facility: Sun yet-sen Memorial Hospital, Sun yet-sen Univesity
city: Hangzhou
country: China
facility: 2nd Affiliated Hosp Zhejiang University College of Medical
city: Hangzhou
country: China
facility: Zhejiang Province People's Hospital
city: Nanchang
country: China
facility: The Second Affiliated Hospital to Nanchang University
city: Nanjing, Jiangsu Province
country: China
facility: Jiangsu Province Hospital
city: Shanghai
country: China
facility: Shanghai First People's Hospital
city: Urumqi
country: China
facility: The First Affiliated Hospital of Xinjiang Medical University
city: Wenzhou
country: China
facility: The First Affiliated Hospital of Wenzhou Med College
Study officials:
References: