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Res Pract Thromb Haemost. 2018 Mar 25;2(2):347-356. doi: 10.1002/rth2.12086. eCollection 2018 Apr.

Design and rationale for the DIVERSITY study: An open-label, randomized study of dabigatran etexilate for pediatric venous thromboembolism.

Author information

1
Hematology Department University Children's Hospital Zürich Switzerland.
2
Department of Clinical Development Boehringer Ingelheim RCV GmbH & Co. KG Vienna Austria.
3
Department for Pediatrics Baylor College of Medicine Houston TX USA.
4
Department of Pediatrics Division of Hematology/Oncology University of Toronto The Hospital for Sick Children Toronto ON Canada.
5
Clinical Development and Medical Affairs Boehringer Ingelheim Pharma GmbH& Co. KG Ingelheim Germany.
6
Faculty of Medicine Mannheim University of Heidelberg Mannheim Germany.
7
Royal Hospital for Children Glasgow Scotland.
8
Boehringer Ingelheim Ltd Bracknell Berkshire UK.
9
Translational Medicine and Clinical Pharmacology Boehringer Ingelheim Pharmaceuticals, Inc. Ridgefield CT USA.
10
OncoHematology Department Bambino Gesù Children's Hospital Rome Italy.
11
University of Alberta Edmonton AB Canada.
12
Biostatistics and Data Sciences Boehringer Ingelheim Pharmaceuticals, Inc. Ridgefield CT USA.
13
Children's Hospital of Eastern Ontario University of Ottawa Ottawa ON Canada.

Abstract

Background:

The current standard of care (SOC) for pediatric venous thromboembolism (VTE) comprises unfractionated heparin (UFH), or low-molecular-weight heparin (LMWH) followed by LMWH or vitamin K antagonists, all of which have limitations. Dabigatran etexilate (DE) has demonstrated efficacy and safety for adult VTE and has the potential to overcome some of the limitations of the current SOC. Pediatric trials are needed to establish dosing in children and to confirm that results obtained in adults are applicable in the pediatric setting.

Objectives:

To describe the design and rationale of a planned phase IIb/III trial that will evaluate a proposed dosing algorithm for DE and assess the safety and efficacy of DE versus SOC for pediatric VTE treatment.

Patients/Methods:

An open-label, randomized, parallel-group noninferiority study will be conducted in approximately 180 patients aged 0 to <18 years with VTE, who have received initial UFH or LMWH treatment and who are expected to require ≥3 months of anticoagulation therapy. Patients will receive DE or SOC for 3 months. DE will be administered twice daily as capsules, pellets, or an oral liquid formulation according to patient age. Initial doses will be calculated using a proposed dosing algorithm.

Results:

There will be two coprimary endpoints: a composite efficacy endpoint comprising the proportion of patients with complete thrombus resolution, freedom from recurrent VTE and VTE-related mortality, and a safety endpoint: freedom from major bleeding events.

Conclusion:

Findings will provide valuable information regarding the efficacy and safety of DE for the treatment of pediatric VTE. ClinicalTrials.gov registration number: NCT01895777.

KEYWORDS:

anticoagulants; dabigatran etexilate; direct thrombin inhibitors; pediatrics; venous thromboembolism

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