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.
Brief Title
Reversal of Dabigatran Anticoagulant Effect With Idarucizumab
Categories
Completion Date
Completion Date Type
Actual
Conditions
Hemorrhage
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).
* 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).
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.
* 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.
Gender
All
Gender Based
false
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT02104947
Org Class
Industry
Org Full Name
Boehringer Ingelheim
Org Study Id
1321.3
Overall Status
Completed
Phases
Phase 3
Primary Completion Date
Primary Completion Date Type
Actual
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
Primary Outcomes
Outcome Description
Maximum reversal of anticoagulant effect of dabigatran based on central laboratory determination of diluted thrombin time (dTT) or ecarin clotting time (ECT), at any time point from the end of the first infusion up to 4 hours after the last infusion.
Reversal is defined for patients with at least one post-dose coagulation test results and pre-dose result higher than 100% ULN (evaluable patients).
Reversal is calculated as 100\* (pre-dose value minus post dose value)/(pre-dose value minus 100% x ULN); if calculated reversal is \> 100, it was set to 100.
Reversal is defined for patients with at least one post-dose coagulation test results and pre-dose result higher than 100% ULN (evaluable patients).
Reversal is calculated as 100\* (pre-dose value minus post dose value)/(pre-dose value minus 100% x ULN); if calculated reversal is \> 100, it was set to 100.
Outcome Measure
Maximum Reversal of Anticoagulant Effect of Dabigatran Based on Central Laboratory Determination of dTT or ECT
Outcome Time Frame
from the end of the first infusion up to 4 hours after the last infusion on Day 1
Secondary Ids
Secondary Id
2013-004813-41
Secondary Outcomes
Outcome Description
Reversal of anticoagulation as measured by Activated Partial Thromboplastin Time (aPTT) and Thrombin time (TT), at any time point since the end of first infusion up to 4 hours after the completion of the last infusion. Reversal is defined for patients with at least one post-dose coagulation test results and pre-dose result higher than 100% ULN (evaluable patients).
Reversal is calculated as 100\* (pre-dose value minus post dose value)/(pre-dose value minus 100% x ULN); if calculated reversal is \> 100, it was set to 100.
Reversal is calculated as 100\* (pre-dose value minus post dose value)/(pre-dose value minus 100% x ULN); if calculated reversal is \> 100, it was set to 100.
Outcome Time Frame
from the end of the first infusion up to 4 hours after the last infusion on Day 1
Outcome Measure
Reversal of aPTT and TT From Central Laboratory
Outcome Description
Duration of reversal, defined as the time period a patient remained completely reversed based on dTT or ECT, up to 24 hours or re-starting the treatment of dabigatran.
Outcome Time Frame
from the first infusion up to 24 hours after the last infusion on Day 1
Outcome Measure
Duration of Reversal
Outcome Description
Occurrence of major/life-threatening/fatal bleeding (for group B only) intraoperatively and up to 24 hours post-surgery were classified according to major or life-threatening bleeding (ISTH \[International Society for Thrombosis and Hemostasis\] definition). 95% Confidence Interval (CI) is from Clopper-Pearson method.
Outcome Time Frame
within 24 hours of surgery
Outcome Measure
Occurrence of Major/Life-threatening/Fatal Bleeding (for Group B Only) Intraoperatively
Outcome Description
Time to cessation of bleeding (for Group A only) since first infusion up to 24 hours after the completion of second infusion; bleeding status was to be categorized before and at several time points after treatment.
Outcome Time Frame
from the first infusion up to 24 hours after the last infusion on Day 1
Outcome Measure
Time to Cessation of Bleeding (for Group A Only)
Outcome Description
Cmin,1 (Minimum concentrations at any time point since the end of first vial of idarucizumab up to 4 hours after the completion of second vial) of unbound sum (free) dabigatran, provided that two vials given not more than 15 min apart in group A and B.
Outcome Time Frame
Since the end of first vial of idarucizumab up to 4 hours after the completion of second vial
Outcome Measure
Cmin,1 of Unbound Sum (Free) Dabigatran
Outcome Description
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.
Reversal is defined for patients with at least one post-dose coagulation test results and pre-dose result higher than 100% ULN (evaluable patients). Reversal is calculated as 100\*(pre-dose value minus post dose value)/(pre-dose value minus 100% x ULN); if calculated reversal is \> 100, it was set to 100.
Reversal is defined for patients with at least one post-dose coagulation test results and pre-dose result higher than 100% ULN (evaluable patients). Reversal is calculated as 100\*(pre-dose value minus post dose value)/(pre-dose value minus 100% x ULN); if calculated reversal is \> 100, it was set to 100.
Outcome Time Frame
after the first vial of idarucizumab and before the start of second vial on Day1
Outcome 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
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Kevin Ferrick
Investigator Email
kferrick@montefiore.org
Investigator Phone
718-920-4293