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TropicALL study: Thromboprophylaxis in Children treated for Acute Lymphoblastic Leukemia with Low-molecular-weight heparin: a multicenter randomized controlled trial
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 s...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5424373/ https://www.ncbi.nlm.nih.gov/pubmed/28486976 http://dx.doi.org/10.1186/s12887-017-0877-x |
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author | Klaassen, Irene L. M. Lauw, Mandy N. van de Wetering, Marianne D. Biemond, Bart J. Middeldorp, Saskia Abbink, Floor C. H. Bierings, Marc te Loo, D. Maroeska M. W. Pieters, Rob van der Sluis, Inge M. Tissing, Wim J. E. Michel Zwaan, C. Heleen van Ommen, C. |
author_facet | Klaassen, Irene L. M. Lauw, Mandy N. van de Wetering, Marianne D. Biemond, Bart J. Middeldorp, Saskia Abbink, Floor C. H. Bierings, Marc te Loo, D. Maroeska M. W. Pieters, Rob van der Sluis, Inge M. Tissing, Wim J. E. Michel Zwaan, C. Heleen van Ommen, C. |
author_sort | Klaassen, Irene L. M. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-5424373 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-54243732017-05-10 TropicALL study: Thromboprophylaxis in Children treated for Acute Lymphoblastic Leukemia with Low-molecular-weight heparin: a multicenter randomized controlled trial Klaassen, Irene L. M. Lauw, Mandy N. van de Wetering, Marianne D. Biemond, Bart J. Middeldorp, Saskia Abbink, Floor C. H. Bierings, Marc te Loo, D. Maroeska M. W. Pieters, Rob van der Sluis, Inge M. Tissing, Wim J. E. Michel Zwaan, C. Heleen van Ommen, C. BMC Pediatr Study Protocol 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. BioMed Central 2017-05-10 /pmc/articles/PMC5424373/ /pubmed/28486976 http://dx.doi.org/10.1186/s12887-017-0877-x Text en © The Author(s). 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Study Protocol Klaassen, Irene L. M. Lauw, Mandy N. van de Wetering, Marianne D. Biemond, Bart J. Middeldorp, Saskia Abbink, Floor C. H. Bierings, Marc te Loo, D. Maroeska M. W. Pieters, Rob van der Sluis, Inge M. Tissing, Wim J. E. Michel Zwaan, C. Heleen van Ommen, C. TropicALL study: Thromboprophylaxis in Children treated for Acute Lymphoblastic Leukemia with Low-molecular-weight heparin: a multicenter randomized controlled trial |
title | TropicALL study: Thromboprophylaxis in Children treated for Acute Lymphoblastic Leukemia with Low-molecular-weight heparin: a multicenter randomized controlled trial |
title_full | TropicALL study: Thromboprophylaxis in Children treated for Acute Lymphoblastic Leukemia with Low-molecular-weight heparin: a multicenter randomized controlled trial |
title_fullStr | TropicALL study: Thromboprophylaxis in Children treated for Acute Lymphoblastic Leukemia with Low-molecular-weight heparin: a multicenter randomized controlled trial |
title_full_unstemmed | TropicALL study: Thromboprophylaxis in Children treated for Acute Lymphoblastic Leukemia with Low-molecular-weight heparin: a multicenter randomized controlled trial |
title_short | TropicALL study: Thromboprophylaxis in Children treated for Acute Lymphoblastic Leukemia with Low-molecular-weight heparin: a multicenter randomized controlled trial |
title_sort | tropicall study: thromboprophylaxis in children treated for acute lymphoblastic leukemia with low-molecular-weight heparin: a multicenter randomized controlled trial |
topic | Study Protocol |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5424373/ https://www.ncbi.nlm.nih.gov/pubmed/28486976 http://dx.doi.org/10.1186/s12887-017-0877-x |
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