Clinical trial NCT02815670: 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
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hemorrhage
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2016-06-28
Enrollment: 1
Sex: ALL
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Number of Participants With Drug-related Adverse Events (AEs)
timeFrame: From vial 1 of Idarucizumab until prematurely discontinued of the trial, up to 25 days
Secondary outcomes:
measure: Percent Change of Coagulation Time for Diluted Thrombin Time (dTT) and Ecarin Clotting Time (ECT) at 30 Minutes Post-dose Compared With Pre-dose
timeFrame: At immediately prior to administration of vial 1 of Idarucizumab and 30 minutes (min) post vial 2 administration.
measure: Time to Achieve Reversal of the Dabigatran Effect (Based on the Coagulation Time for dTT and ECT)
timeFrame: From end of vial 2 of Idarucizumab up to 24h.
measure: Duration of Reversal of the Dabigatran Effect Sustained up to 24 Hours Post-dose (Based on the Coagulation Time for dTT and ECT)
timeFrame: From end of vial 2 of Idarucizumab up to 24h.
measure: Number of Participants With Cessation of Bleeding
timeFrame: From vial 1 of Idarucizumab through vial 2 of Idarucizumab, up to 24h 30min.
measure: Number of Participants Per Bleeding Status During the Trial
timeFrame: From vial 1 of Idarucizumab until prematurely discontinued of the trial, up to 25 days
measure: Number of Participants With Clinical Conditions Contributing to Bleeding During the Trial
timeFrame: From vial 1 of Idarucizumab until prematurely discontinued of the trial, up to 25 days
measure: Number of Participants Developing Treatment-emergent Antidrug Antibodies (ADA) With Cross Reactivity to Idarucizumab
timeFrame: At day 25 post vial 2 of Idarucizumab administration, up to 1 day
Other outcomes:
Locations:
city: Kazan
country: Russian Federation
facility: Children Rep.Clin.Hosp of MoH,Cardio Vas.surgery Dept, Kazan
city: Tyumen
country: Russian Federation
facility: Regional Clin.Hosp.1,Congen.heart defects&child.Cardiol.dept
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References:
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.