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BMC Pediatrics
Published in: BMC Pediatrics 1/2017

Open Access 01-12-2017 | Study protocol

TropicALL study: Thromboprophylaxis in Children treated for Acute Lymphoblastic Leukemia with Low-molecular-weight heparin: a multicenter randomized controlled trial

Authors: Irene L. M. Klaassen, Mandy N. Lauw, Marianne D. van de Wetering, Bart J. Biemond, Saskia Middeldorp, Floor C. H. Abbink, Marc Bierings, D. Maroeska M. W. te Loo, Rob Pieters, Inge M. van der Sluis, Wim J. E. Tissing, C. Michel Zwaan, C. Heleen van Ommen

Published in: BMC Pediatrics | Issue 1/2017

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Abstract

Background

Venous thromboembolism (VTE) is a common and severe complication during treatment of acute lymphoblastic leukemia (ALL). An important cause is the intensive use of asparaginase. Prospective cohort studies in which prophylactic low-molecular-weight heparin (LMWH) was used to prevent VTE showed lower VTE risk than in historic control cohorts, with a negligible bleeding risk. However, the efficacy of thromboprophylaxis with LMWH during ALL treatment has never been investigated in a randomized design. Here, we present the protocol of a randomized controlled trial in which the efficacy and safety of thromboprophylaxis with high prophylactic dose LMWH versus no thromboprophylaxis will be assessed in children treated for primary ALL with asparaginase.

Methods/Design

Thromboprophylaxis in Children treated for Acute Lymphoblastic Leukemia with Low-molecular-weight heparin (TropicALL) is a multicenter, randomized controlled open-label trial conducted in the Netherlands. Patients between 1 and 19 years of age with primary ALL, who are treated within the Dutch Childhood Oncology Group (DCOG) ALL-11 or 12 study will be randomized to thromboprophylaxis with LMWH once daily, (dose of 85 IU/kg (intervention arm A)), or to no thromboprophylaxis (arm B, standard of care) during asparaginase courses of ALL treatment. Primary efficacy endpoint is symptomatic objectified VTE during ALL treatment; secondary efficacy endpoints are overall survival and the composite of symptomatic and asymptomatic objectified VTE. Primary safety endpoints are major bleeding, clinically relevant non-major bleeding and minor bleeding. A total of 324 patients will be included to obtain a relative risk reduction of 75% with a power of 80%, using a two-sided test with significance level α = 0.05.

Discussion

This trial will be the first to assess efficacy and safety of thromboprophylaxis with LMWH during asparaginase treatment for ALL in children in a randomized design.

Trail registration

Nederlands Trial Register NTR4707. Registered 30 July 2014.
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Metadata
Title
TropicALL study: Thromboprophylaxis in Children treated for Acute Lymphoblastic Leukemia with Low-molecular-weight heparin: a multicenter randomized controlled trial
Authors
Irene L. M. Klaassen
Mandy N. Lauw
Marianne D. van de Wetering
Bart J. Biemond
Saskia Middeldorp
Floor C. H. Abbink
Marc Bierings
D. Maroeska M. W. te Loo
Rob Pieters
Inge M. van der Sluis
Wim J. E. Tissing
C. Michel Zwaan
C. Heleen van Ommen
Publication date
01-12-2017
Publisher
BioMed Central
Published in
BMC Pediatrics / Issue 1/2017
Electronic ISSN: 1471-2431
DOI
https://doi.org/10.1186/s12887-017-0877-x

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