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Trial record 1 of 1 for:    re-verse-ad
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Reversal of Dabigatran Anticoagulant Effect With Idarucizumab

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT02104947
First Posted: April 7, 2014
Last Update Posted: October 3, 2017
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 evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Boehringer Ingelheim
Results First Submitted: July 21, 2017  
Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition: Hemorrhage
Intervention: Drug: idarucizumab

  Participant Flow
  Hide Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Idarucizumab (Group A) Patients who were treated with dabigatran and who had uncontrolled or life threatening bleeding that required urgent medical or surgical intervention were administered idarucizumab 5 g (two 2.5 g vials) as an intravenous (IV) infusion. A single vial contains 2.5 g of idarucizumab. Patients received a 2.5 g vial of study medication and a second 2.5-g vial within the next 15 minutes.
Idarucizumab (Group B) Patients who were treated with dabigatran and who may not have been bleeding, but required an emergency surgery or other invasive procedure for a condition other than bleeding where therapeutic anticoagulation might have increased the risk of intra- and post-operative bleeding were administered idarucizumab 5 g (two 2.5 g vials) as an intravenous (IV) infusion. A single vial contains 2.5 g of idarucizumab. Patients received a 2.5 g vial of study medication and a second 2.5-g vial within the next 15 minutes.

Participant Flow:   Overall Study
    Idarucizumab (Group A)   Idarucizumab (Group B)
STARTED   301   202 
COMPLETED   222   146 
NOT COMPLETED   79   56 
Withdrawal by Subject                10                3 
Lost to Follow-up                4                4 
Protocol Violation                6                8 
Adverse Event                57                38 
Other than stated above                2                3 



  Baseline Characteristics
  Hide Baseline Characteristics

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Treated set: Treated Set is defined as all patients who were administered idarucizumab.

Reporting Groups
  Description
Idarucizumab (Group A) Patients who were treated with dabigatran and who had uncontrolled or life threatening bleeding that required urgent medical or surgical intervention were administered idarucizumab 5 g (two 2.5 g vials) as an intravenous (IV) infusion. A single vial contains 2.5 g of idarucizumab. Patients received a 2.5 g vial of study medication and a second 2.5-g vial within the next 15 minutes.
Idarucizumab (Group B) Patients who were treated with dabigatran and who may not have been bleeding, but required an emergency surgery or other invasive procedure for a condition other than bleeding where therapeutic anticoagulation might have increased the risk of intra- and post-operative bleeding were administered idarucizumab 5 g (two 2.5 g vials) as an intravenous (IV) infusion. A single vial contains 2.5 g of idarucizumab. Patients received a 2.5 g vial of study medication and a second 2.5-g vial within the next 15 minutes.
Total Total of all reporting groups

Baseline Measures
   Idarucizumab (Group A)   Idarucizumab (Group B)   Total 
Overall Participants Analyzed 
[Units: Participants]
 301   202   503 
Age 
[Units: Years]
Mean (Standard Deviation)
 77.1  (10.4)   75.9  (10.5)   76.6  (10.5) 
Sex: Female, Male 
[Units: Participants]
Count of Participants
     
Female      129  42.9%      100  49.5%      229  45.5% 
Male      172  57.1%      102  50.5%      274  54.5% 


  Outcome Measures
  Hide All Outcome Measures

1.  Primary:   Maximum Reversal of Anticoagulant Effect of Dabigatran Based on Central Laboratory Determination of dTT or ECT   [ Time Frame: from the end of the first infusion up to 4 hours after the last infusion on Day 1 ]

Measure Type Primary
Measure Title Maximum Reversal of Anticoagulant Effect of Dabigatran Based on Central Laboratory Determination of dTT or ECT
Measure 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.

Time Frame from the end of the first infusion up to 4 hours after the last infusion on Day 1  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Treated Set

Reporting Groups
  Description
Idarucizumab (Group A) Patients who were treated with dabigatran and who had uncontrolled or life threatening bleeding that required urgent medical or surgical intervention were administered idarucizumab 5 g (two 2.5 g vials) as an intravenous (IV) infusion. A single vial contains 2.5 g of idarucizumab. Patients received a 2.5 g vial of study medication and a second 2.5-g vial within the next 15 minutes.
Idarucizumab (Group B) Patients who were treated with dabigatran and who may not have been bleeding, but required an emergency surgery or other invasive procedure for a condition other than bleeding where therapeutic anticoagulation might have increased the risk of intra- and post-operative bleeding were administered idarucizumab 5 g (two 2.5 g vials) as an intravenous (IV) infusion. A single vial contains 2.5 g of idarucizumab. Patients received a 2.5 g vial of study medication and a second 2.5-g vial within the next 15 minutes.

Measured Values
   Idarucizumab (Group A)   Idarucizumab (Group B) 
Participants Analyzed 
[Units: Participants]
 301   202 
Maximum Reversal of Anticoagulant Effect of Dabigatran Based on Central Laboratory Determination of dTT or ECT 
[Units: Percentage]
Median (95% Confidence Interval)
   
dTT (# patients evaluable for reversal=244; 152)   100.0 
 (100.0 to 100.0) 
 100.0 
 (100.0 to 100.0) 
ECT (# patients evaluable for reversal=276; 185)   100.0 
 (100.0 to 100.0) 
 100.0 
 (100.0 to 100.0) 

No statistical analysis provided for Maximum Reversal of Anticoagulant Effect of Dabigatran Based on Central Laboratory Determination of dTT or ECT



2.  Secondary:   Reversal of aPTT and TT From Central Laboratory   [ Time Frame: from the end of the first infusion up to 4 hours after the last infusion on Day 1 ]

Measure Type Secondary
Measure Title Reversal of aPTT and TT From Central Laboratory
Measure 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.

Time Frame from the end of the first infusion up to 4 hours after the last infusion on Day 1  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Treated Set

Reporting Groups
  Description
Idarucizumab (Group A) Patients who were treated with dabigatran and who had uncontrolled or life threatening bleeding that required urgent medical or surgical intervention were administered idarucizumab 5 g (two 2.5 g vials) as an intravenous (IV) infusion. A single vial contains 2.5 g of idarucizumab. Patients received a 2.5 g vial of study medication and a second 2.5-g vial within the next 15 minutes.
Idarucizumab (Group B) Patients who were treated with dabigatran and who may not have been bleeding, but required an emergency surgery or other invasive procedure for a condition other than bleeding where therapeutic anticoagulation might have increased the risk of intra- and post-operative bleeding were administered idarucizumab 5 g (two 2.5 g vials) as an intravenous (IV) infusion. A single vial contains 2.5 g of idarucizumab. Patients received a 2.5 g vial of study medication and a second 2.5-g vial within the next 15 minutes.

Measured Values
   Idarucizumab (Group A)   Idarucizumab (Group B) 
Participants Analyzed 
[Units: Participants]
 301   202 
Reversal of aPTT and TT From Central Laboratory 
[Units: Percentage]
Median (95% Confidence Interval)
   
aPTT (# patients evaluable for reversal=232; 141)   100.0 
 (100.0 to 100.0) 
 100.0 
 (100.0 to 100.0) 
TT (# patients evaluable for reversal=278; 188)   100.0 
 (100.0 to 100.0) 
 100.0 
 (100.0 to 100.0) 

No statistical analysis provided for Reversal of aPTT and TT From Central Laboratory



3.  Secondary:   Duration of Reversal   [ Time Frame: from the first infusion up to 24 hours after the last infusion on Day 1 ]

Measure Type Secondary
Measure Title Duration of Reversal
Measure 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.
Time Frame from the first infusion up to 24 hours after the last infusion on Day 1  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Treated Set

Reporting Groups
  Description
Idarucizumab (Group A) Patients who were treated with dabigatran and who had uncontrolled or life threatening bleeding that required urgent medical or surgical intervention were administered idarucizumab 5 g (two 2.5 g vials) as an intravenous (IV) infusion. A single vial contains 2.5 g of idarucizumab. Patients received a 2.5 g vial of study medication and a second 2.5-g vial within the next 15 minutes.
Idarucizumab (Group B) Patients who were treated with dabigatran and who may not have been bleeding, but required an emergency surgery or other invasive procedure for a condition other than bleeding where therapeutic anticoagulation might have increased the risk of intra- and post-operative bleeding were administered idarucizumab 5 g (two 2.5 g vials) as an intravenous (IV) infusion. A single vial contains 2.5 g of idarucizumab. Patients received a 2.5 g vial of study medication and a second 2.5-g vial within the next 15 minutes.

Measured Values
   Idarucizumab (Group A)   Idarucizumab (Group B) 
Participants Analyzed 
[Units: Participants]
 301   202 
Duration of Reversal 
[Units: Hours]
Mean (Standard Deviation)
   
ECT (# patients evaluable for reversal=276; 185)   13.2  (10.0)   12.8  (9.7) 
dTT (# patients evaluable for reversal=244; 152)   19.8  (6.7)   18.8  (7.6) 

No statistical analysis provided for Duration of Reversal



4.  Secondary:   Occurrence of Major/Life-threatening/Fatal Bleeding (for Group B Only) Intraoperatively   [ Time Frame: within 24 hours of surgery ]

Measure Type Secondary
Measure Title Occurrence of Major/Life-threatening/Fatal Bleeding (for Group B Only) Intraoperatively
Measure 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.
Time Frame within 24 hours of surgery  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Treated Set

Reporting Groups
  Description
Idarucizumab (Group B) Patients who were treated with dabigatran and who may not have been bleeding, but required an emergency surgery or other invasive procedure for a condition other than bleeding where therapeutic anticoagulation might have increased the risk of intra- and post-operative bleeding were administered idarucizumab 5 g (two 2.5 g vials) as an intravenous (IV) infusion. A single vial contains 2.5 g of idarucizumab. Patients received a 2.5 g vial of study medication and a second 2.5-g vial within the next 15 minutes.

Measured Values
   Idarucizumab (Group B) 
Participants Analyzed 
[Units: Participants]
 202 
Occurrence of Major/Life-threatening/Fatal Bleeding (for Group B Only) Intraoperatively 
[Units: Percentage of participants]
Number (95% Confidence Interval)
 3.0 
 (1.1 to 6.5) 

No statistical analysis provided for Occurrence of Major/Life-threatening/Fatal Bleeding (for Group B Only) Intraoperatively



5.  Secondary:   Time to Cessation of Bleeding (for Group A Only)   [ Time Frame: from the first infusion up to 24 hours after the last infusion on Day 1 ]

Measure Type Secondary
Measure Title Time to Cessation of Bleeding (for Group A Only)
Measure 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.
Time Frame from the first infusion up to 24 hours after the last infusion on Day 1  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Treated set with patients who stopped bleeding within 24 hours

Reporting Groups
  Description
ICH (Group A) Group A patients with baseline intracranial hemorrhage (ICH).
Non-ICH (Group A) Group A patients with baseline non-intracranial hemorrhage (non-ICH).

Measured Values
   ICH (Group A)   Non-ICH (Group A) 
Participants Analyzed 
[Units: Participants]
 41   134 
Time to Cessation of Bleeding (for Group A Only) 
[Units: Hours]
Median (95% Confidence Interval)
 10.73 
 (4.80 to 15.73) 
 2.49 
 (2.18 to 3.93) 

No statistical analysis provided for Time to Cessation of Bleeding (for Group A Only)



6.  Secondary:   Cmin,1 of Unbound Sum (Free) Dabigatran   [ Time Frame: Since the end of first vial of idarucizumab up to 4 hours after the completion of second vial ]

Measure Type Secondary
Measure Title Cmin,1 of Unbound Sum (Free) Dabigatran
Measure 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.
Time Frame Since the end of first vial of idarucizumab up to 4 hours after the completion of second vial  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The Pharmacokinetic Set (PKS): This analysis set was used for all PK analyses and was defined as all patients in the Treated Set who provided at least one PK data point.

Reporting Groups
  Description
Idarucizumab (Group A & B)

In Group A the patients who were treated with dabigatran and who had uncontrolled or life threatening bleeding that required urgent medical or surgical intervention were administered idarucizumab 5 g (two 2.5 g vials) as an intravenous (IV) infusion. A single vial contains 2.5 g of idarucizumab. Patients received a 2.5 g vial of study medication and a second 2.5-g vial within the next 15 minutes.

In Group B the patients who were treated with dabigatran and who may not have been bleeding, but required an emergency surgery or other invasive procedure for a condition other than bleeding where therapeutic anticoagulation might have increased the risk of intra- and post-operative bleeding were administered idarucizumab 5 g (two 2.5 g vials) as an intravenous (IV) infusion. A single vial contains 2.5 g of idarucizumab. Patients received a 2.5 g vial of study medication and a second 2.5-g vial within the next 15 minutes.


Measured Values
   Idarucizumab (Group A & B) 
Participants Analyzed 
[Units: Participants]
 493 
Cmin,1 of Unbound Sum (Free) Dabigatran 
[Units: ng/mL]
Geometric Mean (Geometric Coefficient of Variation)
 1.12 
 (61.2%) 

No statistical analysis provided for Cmin,1 of Unbound Sum (Free) Dabigatran



7.  Secondary:   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   [ Time Frame: after the first vial of idarucizumab and before the start of second vial on Day1 ]

Measure Type Secondary
Measure Title 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
Measure 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.

Time Frame after the first vial of idarucizumab and before the start of second vial on Day1  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Treated Set

Reporting Groups
  Description
Idarucizumab (Group A) Patients who were treated with dabigatran and who had uncontrolled or life threatening bleeding that required urgent medical or surgical intervention were administered idarucizumab 5 g (two 2.5 g vials) as an intravenous (IV) infusion. A single vial contains 2.5 g of idarucizumab. Patients received a 2.5 g vial of study medication and a second 2.5-g vial within the next 15 minutes.
Idarucizumab (Group B) Patients who were treated with dabigatran and who may not have been bleeding, but required an emergency surgery or other invasive procedure for a condition other than bleeding where therapeutic anticoagulation might have increased the risk of intra- and post-operative bleeding were administered idarucizumab 5 g (two 2.5 g vials) as an intravenous (IV) infusion. A single vial contains 2.5 g of idarucizumab. Patients received a 2.5 g vial of study medication and a second 2.5-g vial within the next 15 minutes.

Measured Values
   Idarucizumab (Group A)   Idarucizumab (Group B) 
Participants Analyzed 
[Units: Participants]
 301   202 
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 
[Units: Percentage]
Median (95% Confidence Interval)
   
dTT (# patients evaluable for reversal=240; 150)   100.0 
 (100.0 to 100.0) 
 100.0 
 (100.0 to 100.0) 
ECT (# patients evaluable for reversal=271; 182)   100.0 
 (100.0 to 100.0) 
 100.0 
 (100.0 to 100.0) 

No statistical analysis provided for 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




  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
  Hide Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.


  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Boehringer Ingelheim, Call Center
Organization: Boehringer Ingelheim
phone: 1-800-243-0127
e-mail: clintriage.rdg@boehringer-ingelheim.com


Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT02104947     History of Changes
Other Study ID Numbers: 1321.3
2013-004813-41 ( EudraCT Number: EudraCT )
First Submitted: April 2, 2014
First Posted: April 7, 2014
Results First Submitted: July 21, 2017
Results First Posted: August 18, 2017
Last Update Posted: October 3, 2017