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Rationale and design of a phase III safety trial of idarucizumab in children receiving dabigatran etexilate for venous thromboembolism


Albisetti, Manuela; Schlosser, Arno; Brueckmann, Martina; Gropper, Savion; Glund, Stephan; Tartakovsky, Igor; Brandão, Leonardo R; Reilly, Paul A (2018). Rationale and design of a phase III safety trial of idarucizumab in children receiving dabigatran etexilate for venous thromboembolism. Research and Practice in Thrombosis and Haemostasis, 2(1):69-76.

Abstract

Background
The incidence of venous thromboembolism (VTE) in children has been increasing. Anticoagulants are the mainstay of treatment but are associated with bleeding events that may be life-threatening. Idarucizumab is a fragment antigen-binding (fab) that provides immediate, complete, and sustained reversal of dabigatran's anticoagulant effects in adults.

Objective and Methods
This phase III, open-label, single-arm, multicenter, multinational trial will assess the safety of idarucizumab in children participating in two ongoing trials investigating dabigatran etexilate. Eligible patients will be children with VTE (aged 0-≤18 years; n = ~5) with life-threatening or uncontrolled bleeding (group A), and children who require emergency surgery/urgent procedures for a condition other than bleeding (group B). Patients will receive idarucizumab up to 5 g as two consecutive intravenous infusions over 5-10 minutes each, as two 10-15-minute drips or as two bolus injections (15 minutes apart) and will be monitored for 30 days. The primary endpoint will be the safety of idarucizumab assessed by the occurrence of drug-related adverse events (including immune reactions) and all-cause mortality. Secondary endpoints will be the reversal of dabigatran anticoagulant effects assessed by changes in diluted thrombin time and ecarin clotting time, time to achieve complete reversal and the duration of the reversal and bleeding severity (group A). The formation of antidrug antibodies at 30 days post-dose and cessation of bleeding will also be assessed.

Conclusion
This study will report the safety of idarucizumab in children with VTE who require rapid reversal of the anticoagulant effects of dabigatran. Clinical trial registration: NCT02815670.

Abstract

Background
The incidence of venous thromboembolism (VTE) in children has been increasing. Anticoagulants are the mainstay of treatment but are associated with bleeding events that may be life-threatening. Idarucizumab is a fragment antigen-binding (fab) that provides immediate, complete, and sustained reversal of dabigatran's anticoagulant effects in adults.

Objective and Methods
This phase III, open-label, single-arm, multicenter, multinational trial will assess the safety of idarucizumab in children participating in two ongoing trials investigating dabigatran etexilate. Eligible patients will be children with VTE (aged 0-≤18 years; n = ~5) with life-threatening or uncontrolled bleeding (group A), and children who require emergency surgery/urgent procedures for a condition other than bleeding (group B). Patients will receive idarucizumab up to 5 g as two consecutive intravenous infusions over 5-10 minutes each, as two 10-15-minute drips or as two bolus injections (15 minutes apart) and will be monitored for 30 days. The primary endpoint will be the safety of idarucizumab assessed by the occurrence of drug-related adverse events (including immune reactions) and all-cause mortality. Secondary endpoints will be the reversal of dabigatran anticoagulant effects assessed by changes in diluted thrombin time and ecarin clotting time, time to achieve complete reversal and the duration of the reversal and bleeding severity (group A). The formation of antidrug antibodies at 30 days post-dose and cessation of bleeding will also be assessed.

Conclusion
This study will report the safety of idarucizumab in children with VTE who require rapid reversal of the anticoagulant effects of dabigatran. Clinical trial registration: NCT02815670.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Children's Hospital Zurich > Medical Clinic
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:January 2018
Deposited On:30 Jan 2019 08:43
Last Modified:30 Jan 2020 14:00
Publisher:Wiley-Blackwell Publishing, Inc.
ISSN:2475-0379
OA Status:Closed
Publisher DOI:https://doi.org/10.1002/rth2.12053
PubMed ID:30046708

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