Back to resultsReversal Dabigatran Anticoagulant Effect With Idarucizumab
Primary Purpose
Hemorrhage
Status
Completed
Phase
Phase 3
Locations
Russian Federation
Study Type
Interventional
Intervention
Idarucizumab
Sponsored by
About this trial
This is an interventional treatment trial for Hemorrhage
Eligibility Criteria
Inclusion criteria:
Patients taking dabigatran etexilate in the paediatric trials 1160.106 or 1160.108 are eligible for this trial if they meet the following criteria:
Group A:
- Overt bleeding judged by the treating physician to require a reversal agent.
- Currently taking dabigatran etexilate in the context of a clinical trial with dabigatran etexilate (1160.106 or 1160.108).
- Male or female patients from 0 to less than 18 years of age at the time of informed consent/assent for participation in trial 1160.106 or in trial 1160.108.
- Female patients of childbearing potential (defined as having experienced menarche) must have followed the contraception requirements according to the dabigatran trial 1160.106 or trial 1160.108 in which they are enrolled.
- Written informed consent provided by the patient (and/or the patient's legally accepted representative) and assent provided by the patient (if applicable) at the time of informed consent signature in accordance with Good Clinical Practice (GCP) and local legislation prior to admission to the trial. If the child is unable to give assent at the time of the emergency, the assent, when applicable will be obtained as soon as feasible.
Group B:
- A condition requiring an emergency surgery or invasive procedure where adequate haemostasis is required. Emergency is defined as need for surgery or intervention within the following 8 hours.
- Currently taking dabigatran etexilate in the context of a clinical trial with dabigatran etexilate (1160.106 or 1160.108).
- Male or female patients from 0 to less than 18 years of age at the time of informed consent/assent for participation in trial 1160.106 or in trial 1160.108.
- Female patients of childbearing potential (defined as having experienced menarche) must have followed the contraception requirements according to the dabigatran trial 1160.106 or trial 1160.108 in which they are enrolled.
- Written informed consent provided by the patient (and/or the patient's legally accepted representative) and assent provided by the patient (if applicable) at the time of informed consent signature in accordance with GCP and local legislation prior to admission to the trial. If the child is unable to give assent at the time of the emergency, the assent, when applicable will be obtained as soon as feasible.
Exclusion criteria:
Group A:
- Patients with minor bleeding (e.g. epistaxis, haematuria) who can be managed with standard supportive care.
- Patients with no clinical signs of bleeding.
- Patients with body weight < 2.5 kg
- Contraindications to trial medication including known hypersensitivity to the drug or its excipients; i.e. patients with hereditary fructose intolerance who may react to sorbitol.
- Female patients who are pregnant, nursing, or who plan to become pregnant while in the trial.
Group B:
- A surgery or procedure which is elective or where the risk of uncontrolled or unmanageable bleeding is low.
- Patients with body weight < 2.5 kg
- Contraindications to trial medication including known hypersensitivity to the drug or its excipients; i.e. patients with hereditary fructose intolerance who may react to sorbitol.
- Female patients who are pregnant, nursing, or who plan to become pregnant while in the trial.
Sites / Locations
- Children Rep.Clin.Hosp of MoH,Cardio Vas.surgery Dept, Kazan
- Regional Clin.Hosp.1,Congen.heart defects&child.Cardiol.dept
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Idarucizumab
Arm Description
Outcomes
Primary Outcome Measures
Number of Participants With Drug-related Adverse Events (AEs)
Number of participants with drug-related adverse events (AEs) including immune reactions and all cause mortality during the trial.
Secondary Outcome Measures
Percent Change of Coagulation Time for Diluted Thrombin Time (dTT) and Ecarin Clotting Time (ECT) at 30 Minutes Post-dose Compared With Pre-dose
Percent change of coagulation time for diluted thrombin time (dTT) and ecarin clotting time (ECT) at 30 minutes (min) post-dose compared with pre-dose. Central blood sampling for dTT, ECT were to occur immediately prior to administration of each vial of Idarucizumab and post-dose at 30min, 4h, 12h and 24h.
Time to Achieve Reversal of the Dabigatran Effect (Based on the Coagulation Time for dTT and ECT)
Idarucizumab administration resulted in normalisation of dTT and ECT. Time to achieve reversal of anticoagulant effect of dabigatran based on the coagulation time for dTT and ECT, at any time point from the end of the second injection (vial 2) up to 24 hours (h). Reversal of the dabigatran effect at time t was defined as the 100 percent (%) *(pre-dose coagulation time - post-dose coagulation time at time t)/(pre-dose coagulation test - upper limit of normal).
Values equal to or higher than 100% were interpreted as reversal. Central blood sampling for dTT, ECT were to occur immediately prior to administration of each vial of Idarucizumab and post-dose at 30min, 4h, 12h and 24h.
Duration of Reversal of the Dabigatran Effect Sustained up to 24 Hours Post-dose (Based on the Coagulation Time for dTT and ECT)
Duration of reversal, defined as the time period a patient remained completely reversed based on dTT and ECT, up to 24 hours post-dose or restarting the treatment of anticoagulation. Central blood sampling for dTT, ECT were to occur immediately prior to administration of each vial of idarucizumab and post-dose at 30min, 4h, 12h and 24h.
Number of Participants With Cessation of Bleeding
Number of Participants Per Bleeding Status During the Trial
Numbers of participants whose bleeding had stopped, reduced, unchanged, worsened or not applicable during the trial were characterized.
Number of Participants With Clinical Conditions Contributing to Bleeding During the Trial
Number of participants with clinical conditions (trauma, surgery and use of antiplatelet) contributing to bleeding during the trial were characterized.
Number of Participants Developing Treatment-emergent Antidrug Antibodies (ADA) With Cross Reactivity to Idarucizumab
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02815670
Brief Title
Reversal Dabigatran Anticoagulant Effect With Idarucizumab
Official Title
Single Dose, Open Label, Uncontrolled, Safety Trial of Intravenous Administration of Idarucizumab to Paediatric Patients Enrolled From Ongoing Phase IIb/III Clinical Trials With Dabigatran Etexilate for the Treatment and Secondary Prevention of Venous Thromboembolism.
Study Type
Interventional
2. Study Status
Record Verification Date
March 2020
Overall Recruitment Status
Completed
Study Start Date
September 7, 2016 (Actual)
Primary Completion Date
October 19, 2019 (Actual)
Study Completion Date
October 19, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Boehringer Ingelheim
4. Oversight
5. Study Description
Brief Summary
The trial objective is to demonstrate the safety of idarucizumab, as assessed by the occurence of patients with drug related adverse events (including immune reactions) and all-cause mortality in paediatric venous thromboembolism patients treated with dabigatran in ongoing clinical trials who require emergency surgery/urgent procedures or patients who have life-threatening or uncontrolled bleeding which requires urgent intervention, when rapid reversal of the anticoagulant effect of dabigatran is needed.
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
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
1 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Idarucizumab
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Idarucizumab
Primary Outcome Measure Information:
Title
Number of Participants With Drug-related Adverse Events (AEs)
Description
Number of participants with drug-related adverse events (AEs) including immune reactions and all cause mortality during the trial.
Time Frame
From vial 1 of Idarucizumab until prematurely discontinued of the trial, up to 25 days
Secondary Outcome Measure Information:
Title
Percent Change of Coagulation Time for Diluted Thrombin Time (dTT) and Ecarin Clotting Time (ECT) at 30 Minutes Post-dose Compared With Pre-dose
Description
Percent change of coagulation time for diluted thrombin time (dTT) and ecarin clotting time (ECT) at 30 minutes (min) post-dose compared with pre-dose. Central blood sampling for dTT, ECT were to occur immediately prior to administration of each vial of Idarucizumab and post-dose at 30min, 4h, 12h and 24h.
Time Frame
At immediately prior to administration of vial 1 of Idarucizumab and 30 minutes (min) post vial 2 administration.
Title
Time to Achieve Reversal of the Dabigatran Effect (Based on the Coagulation Time for dTT and ECT)
Description
Idarucizumab administration resulted in normalisation of dTT and ECT. Time to achieve reversal of anticoagulant effect of dabigatran based on the coagulation time for dTT and ECT, at any time point from the end of the second injection (vial 2) up to 24 hours (h). Reversal of the dabigatran effect at time t was defined as the 100 percent (%) *(pre-dose coagulation time - post-dose coagulation time at time t)/(pre-dose coagulation test - upper limit of normal).
Values equal to or higher than 100% were interpreted as reversal. Central blood sampling for dTT, ECT were to occur immediately prior to administration of each vial of Idarucizumab and post-dose at 30min, 4h, 12h and 24h.
Time Frame
From end of vial 2 of Idarucizumab up to 24h.
Title
Duration of Reversal of the Dabigatran Effect Sustained up to 24 Hours Post-dose (Based on the Coagulation Time for dTT and ECT)
Description
Duration of reversal, defined as the time period a patient remained completely reversed based on dTT and ECT, up to 24 hours post-dose or restarting the treatment of anticoagulation. Central blood sampling for dTT, ECT were to occur immediately prior to administration of each vial of idarucizumab and post-dose at 30min, 4h, 12h and 24h.
Time Frame
From end of vial 2 of Idarucizumab up to 24h.
Title
Number of Participants With Cessation of Bleeding
Time Frame
From vial 1 of Idarucizumab through vial 2 of Idarucizumab, up to 24h 30min.
Title
Number of Participants Per Bleeding Status During the Trial
Description
Numbers of participants whose bleeding had stopped, reduced, unchanged, worsened or not applicable during the trial were characterized.
Time Frame
From vial 1 of Idarucizumab until prematurely discontinued of the trial, up to 25 days
Title
Number of Participants With Clinical Conditions Contributing to Bleeding During the Trial
Description
Number of participants with clinical conditions (trauma, surgery and use of antiplatelet) contributing to bleeding during the trial were characterized.
Time Frame
From vial 1 of Idarucizumab until prematurely discontinued of the trial, up to 25 days
Title
Number of Participants Developing Treatment-emergent Antidrug Antibodies (ADA) With Cross Reactivity to Idarucizumab
Time Frame
At day 25 post vial 2 of Idarucizumab administration, up to 1 day
10. Eligibility
Sex
All
Maximum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion criteria:
Patients taking dabigatran etexilate in the paediatric trials 1160.106 or 1160.108 are eligible for this trial if they meet the following criteria:
Group A:
Overt bleeding judged by the treating physician to require a reversal agent.
Currently taking dabigatran etexilate in the context of a clinical trial with dabigatran etexilate (1160.106 or 1160.108).
Male or female patients from 0 to less than 18 years of age at the time of informed consent/assent for participation in trial 1160.106 or in trial 1160.108.
Female patients of childbearing potential (defined as having experienced menarche) must have followed the contraception requirements according to the dabigatran trial 1160.106 or trial 1160.108 in which they are enrolled.
Written informed consent provided by the patient (and/or the patient's legally accepted representative) and assent provided by the patient (if applicable) at the time of informed consent signature in accordance with Good Clinical Practice (GCP) and local legislation prior to admission to the trial. If the child is unable to give assent at the time of the emergency, the assent, when applicable will be obtained as soon as feasible.
Group B:
A condition requiring an emergency surgery or invasive procedure where adequate haemostasis is required. Emergency is defined as need for surgery or intervention within the following 8 hours.
Currently taking dabigatran etexilate in the context of a clinical trial with dabigatran etexilate (1160.106 or 1160.108).
Male or female patients from 0 to less than 18 years of age at the time of informed consent/assent for participation in trial 1160.106 or in trial 1160.108.
Female patients of childbearing potential (defined as having experienced menarche) must have followed the contraception requirements according to the dabigatran trial 1160.106 or trial 1160.108 in which they are enrolled.
Written informed consent provided by the patient (and/or the patient's legally accepted representative) and assent provided by the patient (if applicable) at the time of informed consent signature in accordance with GCP and local legislation prior to admission to the trial. If the child is unable to give assent at the time of the emergency, the assent, when applicable will be obtained as soon as feasible.
Exclusion criteria:
Group A:
Patients with minor bleeding (e.g. epistaxis, haematuria) who can be managed with standard supportive care.
Patients with no clinical signs of bleeding.
Patients with body weight < 2.5 kg
Contraindications to trial medication including known hypersensitivity to the drug or its excipients; i.e. patients with hereditary fructose intolerance who may react to sorbitol.
Female patients who are pregnant, nursing, or who plan to become pregnant while in the trial.
Group B:
A surgery or procedure which is elective or where the risk of uncontrolled or unmanageable bleeding is low.
Patients with body weight < 2.5 kg
Contraindications to trial medication including known hypersensitivity to the drug or its excipients; i.e. patients with hereditary fructose intolerance who may react to sorbitol.
Female patients who are pregnant, nursing, or who plan to become pregnant while in the trial.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Boehringer Ingelheim
Organizational Affiliation
Boehringer Ingelheim
Official's Role
Study Chair
Facility Information:
Facility Name
Children Rep.Clin.Hosp of MoH,Cardio Vas.surgery Dept, Kazan
City
Kazan
ZIP/Postal Code
420138
Country
Russian Federation
Facility Name
Regional Clin.Hosp.1,Congen.heart defects&child.Cardiol.dept
City
Tyumen
ZIP/Postal Code
625021
Country
Russian Federation
12. IPD Sharing Statement
Citations:
PubMed Identifier
30046708
Citation
Albisetti M, Schlosser A, Brueckmann M, Gropper S, Glund S, Tartakovsky I, Brandao LR, Reilly PA. Rationale and design of a phase III safety trial of idarucizumab in children receiving dabigatran etexilate for venous thromboembolism. Res Pract Thromb Haemost. 2017 Nov 17;2(1):69-76. doi: 10.1002/rth2.12053. eCollection 2018 Jan.
Results Reference
derived
Links:
URL
https://trials.boehringer-ingelheim.com/
Description
Related Info
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Reversal Dabigatran Anticoagulant Effect With Idarucizumab
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