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.

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.