A multi-national trial of a direct oral anticoagulant in children with cardiac disease

Design and rationale of the Safety of ApiXaban On Pediatric Heart disease On the preventioN of Embolism (SAXOPHONE) study

Pediatric Heart Network Investigators

Research output: Contribution to journalArticle

Abstract

Anticoagulation in children is problematic for multiple reasons. Currently used anticoagulants have significant disadvantages and may negatively affect quality of life (QOL). This manuscript describes the design, rationale, and methods of a prospective, randomized, open label phase II multi-national clinical trial of a direct oral anticoagulant (DOAC), apixaban, in children and infants with congenital and acquired heart disease. This trial is designed to gather preliminary safety and pharmacokinetics (PK) data, as well as generate data on QOL of individuals taking apixaban compared to the standard of care (SOC) anticoagulants vitamin K antagonists (VKA) or low molecular weight heparin (LMWH). A key issue this trial seeks to address is the practice of using therapeutics tested in adult trials in the pediatric population without robust pediatric safety or efficacy data. Pediatric heart diseases are not common, and specific diagnoses often meet the criteria of a rare disease; thus, statistical efficacy may be difficult to achieve. This trial will provide valuable PK and safety data intended to inform clinical practice for anticoagulation in pediatric heart diseases, a setting in which a fully powered phase III clinical trial is not feasible. A second consideration this trial addresses is that metrics besides efficacy, such as QOL, have not been traditionally used as endpoints in regulated anticoagulation studies yet may add substantial weight to the clinical decision for use of a DOAC in place of VKA or LMWH. This study examines QOL related to both heart disease and anticoagulation among children randomized to either SOC or apixaban. There are considerable strengths and benefits to conducting a clinical trial in pediatric rare disease populations via an industry-academic collaboration. The SAXOPHONE study represents a collaboration between Bristol-Myers Squibb (BMS)/Pfizer Alliance, and the National Heart, Lung, and Blood Institute's (NHLBI) Pediatric Heart Network (PHN) and may be an attractive model for future pediatric drug trials.

Original languageEnglish (US)
Pages (from-to)52-63
Number of pages12
JournalAmerican Heart Journal
Volume217
DOIs
StatePublished - Nov 1 2019

Fingerprint

Embolism
Anticoagulants
Heart Diseases
Pediatrics
Safety
Quality of Life
Vitamin K
Low Molecular Weight Heparin
Standard of Care
Rare Diseases
Pharmacokinetics
Clinical Trials
National Heart, Lung, and Blood Institute (U.S.)
Phase III Clinical Trials
apixaban
Population
Industry
Weights and Measures
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

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title = "A multi-national trial of a direct oral anticoagulant in children with cardiac disease: Design and rationale of the Safety of ApiXaban On Pediatric Heart disease On the preventioN of Embolism (SAXOPHONE) study",
abstract = "Anticoagulation in children is problematic for multiple reasons. Currently used anticoagulants have significant disadvantages and may negatively affect quality of life (QOL). This manuscript describes the design, rationale, and methods of a prospective, randomized, open label phase II multi-national clinical trial of a direct oral anticoagulant (DOAC), apixaban, in children and infants with congenital and acquired heart disease. This trial is designed to gather preliminary safety and pharmacokinetics (PK) data, as well as generate data on QOL of individuals taking apixaban compared to the standard of care (SOC) anticoagulants vitamin K antagonists (VKA) or low molecular weight heparin (LMWH). A key issue this trial seeks to address is the practice of using therapeutics tested in adult trials in the pediatric population without robust pediatric safety or efficacy data. Pediatric heart diseases are not common, and specific diagnoses often meet the criteria of a rare disease; thus, statistical efficacy may be difficult to achieve. This trial will provide valuable PK and safety data intended to inform clinical practice for anticoagulation in pediatric heart diseases, a setting in which a fully powered phase III clinical trial is not feasible. A second consideration this trial addresses is that metrics besides efficacy, such as QOL, have not been traditionally used as endpoints in regulated anticoagulation studies yet may add substantial weight to the clinical decision for use of a DOAC in place of VKA or LMWH. This study examines QOL related to both heart disease and anticoagulation among children randomized to either SOC or apixaban. There are considerable strengths and benefits to conducting a clinical trial in pediatric rare disease populations via an industry-academic collaboration. The SAXOPHONE study represents a collaboration between Bristol-Myers Squibb (BMS)/Pfizer Alliance, and the National Heart, Lung, and Blood Institute's (NHLBI) Pediatric Heart Network (PHN) and may be an attractive model for future pediatric drug trials.",
author = "{Pediatric Heart Network Investigators} and R. Payne and Burns, {Kristin M.} and Glatz, {Andrew C.} and Danshi Li and Xiaodong Li and Paul Monagle and Newburger, {Jane W.} and Swan, {Elizabeth A.} and Olivia Wheaton and Christoph Male",
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AU - Pediatric Heart Network Investigators

AU - Payne, R.

AU - Burns, Kristin M.

AU - Glatz, Andrew C.

AU - Li, Danshi

AU - Li, Xiaodong

AU - Monagle, Paul

AU - Newburger, Jane W.

AU - Swan, Elizabeth A.

AU - Wheaton, Olivia

AU - Male, Christoph

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