Reversal of dabigatran anticoagulant effect with idarucizumab.

Phase 1

Conditions: Eligible paediatric patients from trial 1160.106 or 1160.108 treated with dabigatran etexilate who require emergency surgery/urgent procedures requiring rapid reversal of the anticoagulant effect of dabigatran prior to these emergency surgery/urgent procedures or patients who exhibiting signs and symptoms of life-threatening or uncontrolled bleeding requiring urgent medical intervention, could participate.
Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]
MedDRA version: 21.1Level: LLTClassification code 10066899Term: Venous thromboembolismSystem Organ Class: 100000004866
MedDRA version: 21.1Level: LLTClassification code 10049909Term: Venous thromboembolism prophylaxisSystem Organ Class: 100000004865

Registration Number: EUCTR2015-002177-37-DE

Lead Sponsor: Boehringer Ingelheim Pharma GmbH & Co.KG

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 1

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 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.

Are the trial subjects under 18? yes
Number of subjects for this age range: 9
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range 1
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

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 or infants with unknown hereditary fructose intolerance status.
- 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 or infants with unknown hereditary fructose intolerance status.
- Female patients who are pregnant, nursing, or who plan to become pregnant while in the trial.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To demonstrate the safety of idarucizumab, as assessed by the occurrence of patients with drug related adverse events (including immune reactions) and all-cause mortality in paediatric venous thromboembolism (VTE) 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 effects of dabigatran is needed.;Secondary Objective: Assessments of the reversal of dabigatran, bleeding status or emergency surgery/urgent procedures, clinical outcomes, pharmacokinetics of dabigatran and idarucizumab.;Primary end point(s): 1: Safety of idarucizumab in a paediatric population as assessed by the occurrence of drug-related adverse events (including immune reactions) and all-cause mortality during the trial.<br>;Timepoint(s) of evaluation of this end point: 1: 30 days post-dose<br>

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): 1: Percent change of coagulation tests (dTT, ECT) at 30 minutes post-dose compared to pre-dose.<br><br>2: Time to achieve complete reversal of dabigatran effect, based on coagulation tests (dTT and ECT).<br><br>3: Duration of complete reversal of dabigatran effect sustained at 24 hours post-dose, based on coagulation tests (dTT and ECT).<br><br>4: Cessation of bleeding (Group A patients only).<br><br>5: Bleeding status and other clinical conditions that may contribute to bleeding (Group A patients only) during the trial.<br><br>6: Development of treatment-emergent ADA with cross reactivity to idarucizumab at <br>30 days post-dose of idarucizumab (binary).<br><br>;Timepoint(s) of evaluation of this end point: 1: 30 minutes post-dose<br><br>2: Up to 24 hours post-dose<br><br>3: Up to 24 hours post-dose<br><br>4: Up to 24 hours post-dose<br><br>5: 30 days post-dose<br><br>6: 30 days post-dose<br>

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