PREVAPIX-ALL: Apixaban Compared to Standard of Care for Prevention of Venous Thrombosis in Paediatric Acute Lymphoblastic Leukaemia (ALL)—Rationale and Design

Sarah H. O'Brien; Danshi Li; Lesley G. Mitchell; Thomas Hess; Pamela Zee; Donald L. Yee; Jane W. Newburger; Lillian Sung; Vilmarie Rodriguez

doi:10.1055/s-0039-1679938

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 2019; 119(05): 844-853
DOI: 10.1055/s-0039-1679938

Trial Protocol Design Paper

Georg Thieme Verlag KG Stuttgart · New York

PREVAPIX-ALL: Apixaban Compared to Standard of Care for Prevention of Venous Thrombosis in Paediatric Acute Lymphoblastic Leukaemia (ALL)—Rationale and Design

Sarah H. O'Brien

¹Division of Pediatric Hematology/Oncology, Nationwide Children's Hospital/The Ohio State University, Columbus, Ohio, United States

,

Danshi Li

²Cardiovascular, Innovative Medicines Development, Bristol-Myers Squibb, Lawrenceville, New Jersey, United States

,

Lesley G. Mitchell

³Division Pediatric Hematology/Oncology, University of Alberta, Edmonton, Alberta, Canada

,

Thomas Hess

²Cardiovascular, Innovative Medicines Development, Bristol-Myers Squibb, Lawrenceville, New Jersey, United States

,

Pamela Zee

²Cardiovascular, Innovative Medicines Development, Bristol-Myers Squibb, Lawrenceville, New Jersey, United States

,

Donald L. Yee

⁴Hematology-Oncology Section, Department of Pediatrics, Baylor College of Medicine, Houston, Texas, United States

,

Jane W. Newburger

⁵Department of Cardiology, Boston Children's Hospital, Boston, Massachusetts, United States

⁶Department of Pediatrics, Harvard Medical School, Harvard University, Boston, Massachusetts, United States

,

Lillian Sung

⁷Children's Oncology Group Cancer Control Chair, The Hospital for Sick Children, Toronto, Ontario, Canada

,

Vilmarie Rodriguez

⁸Division of Pediatric Hematology/Oncology, Department of Pediatrics and Adolescent Medicine, Mayo Clinic, Rochester, Minnesota, United States

› Institutsangaben

Abstract

Venous thromboembolic (VTE) complications in children and adolescents with acute lymphoblastic leukaemia (ALL) and T or B cell lymphoblastic lymphoma (T/B cell LL) can result not only in life-threatening acute complications but also contribute to significant long-term sequelae. The PREVAPIX-ALL study is an open-label randomized controlled study comparing outcomes of treatment with prophylactic dose apixaban versus no anticoagulation (standard of care) in children and adolescents with ALL and T/B cell LL receiving standard induction chemotherapy with asparaginase and the presence of a central venous access device. On day 29 of induction, all patients undergo screening imaging with duplex ultrasonography and echocardiography. The primary efficacy endpoint of the study is a composite of symptomatic and asymptomatic VTE that includes deep vein thrombosis, pulmonary embolism, cerebral sinovenous thrombosis or VTE-related death. The primary safety outcome is major bleeding. Secondary outcomes are central line-associated infections, patency and line replacement, superficial thrombosis, arterial events and death. A planned sample size of 500 randomized paediatric patients enrolled over a period of 5 years is based on the estimation of VTE rates of 20 and 10% in the standard of care and apixaban groups, respectively. An optional biomarker study in 150 patients will examine predictors of increased VTE risk and study in vivo anticoagulant effects of apixaban in children by measuring specific biomarkers in the haemostatic system and inflammatory pathway. This study will provide valuable information for the safety and efficacy of apixaban in VTE prevention during induction in paediatric ALL.

Keywords

anticoagulation - deep vein thrombosis - direct-acting oral anticoagulant - thromboprophylaxis - children

Volltext

Referenzen

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