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

BMC Pediatrics

Study Protocol

Bart J. Biemond¹  Floor C. H. Abbink²  Marc Bierings³  Irene L. M. Klaassen⁴  D. Maroeska M. W. te Loo⁵  Marianne D. van de Wetering⁶  Wim J. E. Tissing⁷  C. Heleen van Ommen⁸  Inge M. van der Sluis⁸  C. Michel Zwaan⁸  Saskia Middeldorp⁹  Mandy N. Lauw^1,10  Rob Pieters^1,11 

[1] Department of Hematology, Academic Medical Center, Amsterdam, The Netherlands;Department of Hematology/Oncology, VU Medical Center, Amsterdam, The Netherlands;Department of Hematology/Oncology, Wilhelmina Children’s Hospital, Utrecht, The Netherlands;Department of Pediatric Hematology, Academic Medical Center, Amsterdam, The Netherlands;Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands;Department of Pediatric Hematology/Oncology, Radboud University Medical Center, Nijmegen, The Netherlands;Department of Pediatric Oncology, Academic Medical Center, Amsterdam, The Netherlands;Department of Pediatric Oncology, Beatrix Children’s Hospital, University Medical Center Groningen, Groningen, the Netherlands;Department of Pediatric Oncology/Hematology, Erasmus MC-Sophia Children’s Hospital, Rotterdam, The Netherlands;Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands;Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands;Department of Hematology, Academic Medical Center, Amsterdam, The Netherlands;Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands;

关键词: Acute lymphoblastic leukemia;    Low molecular weight heparin;    Venous thromboembolic disease;    Asparaginase;    Pediatric;   

DOI  :  10.1186/s12887-017-0877-x

 received in 2016-11-24, accepted in 2017-04-27,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundVenous 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/DesignThromboprophylaxis 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.DiscussionThis 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 registrationNederlands Trial Register NTR4707. Registered 30 July 2014.

【 授权许可】

CC BY   
© The Author(s). 2017