Reversal Dabigatran Anticoagulant Effect With Idarucizumab

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.

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.

Study Overview

• Status: Completed
• Conditions: Hemorrhage
• Intervention / Treatment: Drug: Idarucizumab

• Study Type: Interventional
• Enrollment (Actual): 1
• Phase: Phase 3

Contacts and Locations

Study Locations

• Russian Federation
  • Kazan, Russian Federation, 420138
    • Children Rep.Clin.Hosp of MoH,Cardio Vas.surgery Dept, Kazan
  • Tyumen, Russian Federation, 625021
    • Regional Clin.Hosp.1,Congen.heart defects&child.Cardiol.dept

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 16 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Idarucizumab	Drug: Idarucizumab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	From vial 1 of Idarucizumab until prematurely discontinued of the trial, up to 25 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	At immediately prior to administration of vial 1 of Idarucizumab and 30 minutes (min) post vial 2 administration.
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.	From end of vial 2 of Idarucizumab up to 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.	From end of vial 2 of Idarucizumab up to 24h.
Number of Participants With Cessation of Bleeding		From vial 1 of Idarucizumab through vial 2 of Idarucizumab, up to 24h 30min.
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.	From vial 1 of Idarucizumab until prematurely discontinued of the trial, up to 25 days
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.	From vial 1 of Idarucizumab until prematurely discontinued of the trial, up to 25 days
Number of Participants Developing Treatment-emergent Antidrug Antibodies (ADA) With Cross Reactivity to Idarucizumab		At day 25 post vial 2 of Idarucizumab administration, up to 1 day

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

General Publications

• 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.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): September 7, 2016
• Primary Completion (Actual): October 19, 2019
• Study Completion (Actual): October 19, 2019

Study Registration Dates

• First Submitted: June 24, 2016
• First Submitted That Met QC Criteria: June 24, 2016
• First Posted (Estimate): June 28, 2016

Study Record Updates

• Last Update Posted (Actual): April 14, 2020
• Last Update Submitted That Met QC Criteria: March 31, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Hemorrhage
• Other Study ID Numbers: 1321.7; 2015-002177-37 (EudraCT Number)