OC 15.2 - The SAXOPHONE Study; A Multi-Center, Multi-National Randomized Trial of Apixaban versus Standard of Care Anticoagulation for Thromboprophylaxis in Children with Congenital or Acquired Heart Disease

Sunday, July 10, 2022

11:00 AM – 11:15 AM

Location: ExCel Center, ICC Capital Suite Room 14-16

Presentation Format: In-Person

Presenting Author(s)

Ronald M. Payne, MD

Professor of Pediatrics, Division of Cardiology
Indiana University School of Medicine
Indianapolis, Indiana, United States

Co-Author(s)

KB

Kristin M. Burns

Program officer
Heart Development and Structural Diseases Branch / Division of Cardiovascular Sciences
Bethesda, Maryland, United States
AG

Andrew C. Glatz

Interventional cardiologist
Children’s Hospital of Philadelphia
Philadelphia, Pennsylvania, United States
Christoph Male, MD, MSc

Head of the Pediatric Hemostasis & Thrombosis Unit
Department of Paediatrics, Medical University of Vienna, Vienna, Austria.
Vienna, Wien, Austria
AD

Andrea Donti

Physician and Pediatric Cardiologist
Azienda Ospedaliera-Universitaria- Ospedale di S. Orsola, Bologna, Italy
Bologna, Emilia-Romagna, Italy
Leonardo R. Brandão, MD, MSc

Staff Hematologist
The Hospital for Sick Children
Toronto, Ontario, Canada
GB

Gunter Balling

Physician and Pediatric Cardiologist
German Heart Center Munich, Technical University Munich
Munich, Bayern, Germany
CV

Christina J. VanderPluym

Assistant Professor and Pediatric Cardiologist
Children’s Hospital, Harvard University
Boston, Massachusetts, United States
FB

Frances Bu'Lock

Consultant Paediatric Cardiologist
East Midlands Congenital Heart Centre, University Hospitals of Leicester NHS Trust
Leicester, England, United Kingdom
LK

Lazaros K. Kochilas

Associate Professor, Pediatric Cardiology
Children’s Healthcare of Atlanta and Emory University, School of Medicine, Department of Pediatrics
Atlanta, Georgia, United States
BS

Brigitte Stiller

Professor of Pediatric Cardiology
Department of Congenital Heart Defects and Pediatric Cardiology, University Heart Center Freiburg-BadKrozingen, University of Freiburg
Freiburg-BadKrozingen, Baden-Wurttemberg, Germany
JC

James F. Cnota, II

Professor of Pediatric Cardiology
Cincinnati Children’s Hospital Medical Center, Cincinnati, OH
Cincinnati, Ohio, United States
AB

Alfonso Buendia

Professor of Pediatric Cardiology
Departamento de Cardiología Pedíatrica, Instituto Nacional de Cardiología
Mexico City, Distrito Federal, Mexico
OR

Otto Rahkonen

Professor of Pediatric Cardiology
New Children's Hospital, University of Helsinki and Helsinki University Hospital
Helsinki, Uusimaa, Finland
OW

Olivia Wheaton

Senior Clinical Research Project Manager
HealthCore
Wilmington, Delaware, United States
AR

Alison M. Reedy

Clinical scientist
Bristol Myers Squibb, Inc
Lawrence Township, New Jersey, United States
JD

Joshua L. Dyme

Senior Clinical Trial Physician
Bristol Myers Squibb
Lawrence Township, New Jersey, United States
LC

Lauren Carlson

Biostatistician
Bristol Myers Squibb, Inc
Lawrence Township, New Jersey, United States
CC

Christina T. Crevar

Global Trial Manager
Bristol Myers Squibb, Inc.
Lawrence Township, New Jersey, United States
Paul Monagle, MD

Professor
Haematology Research, Murdoch Children's Research Institute
Melbourne, Victoria, Australia

Background: Vitamin K antagonists (VKA) or low molecular weight heparin (LMWH) are currently standard of care (SOC) for chronic anticoagulation in children with heart disease. Direct anticoagulants are the preferred SOC for thromboembolism prevention (TE) in adults due to their proven efficacy and safety without need for monitoring.

Aims: SAXOPHONE compared safety and tolerability of apixaban versus SOC for TE prevention in children with heart disease and assessed pharmacokinetics/pharmacodynamics (PK/PD).

Methods: Children 29 days to < 18 years of age with heart disease requiring chronic thromboprophylaxis were randomized 2:1 apixaban:SOC for ≤12 months in this open-label, phase 2, multi-center trial. The primary safety endpoint was major or clinically relevant non-major (CRNM) bleeding. Secondary endpoints were PK/PD and TE. Safety and efficacy events were reviewed by a blinded independent Event Adjudication Committee. Ethics committee review and informed consent were obtained. SAXOPHONE was funded by the Bristol Myers Squibb and Pfizer Alliance, with scientific leadership from NIH’s Pediatric Heart Network.

Results: 198 participants were screened, 192 randomized, 188 treated (126 apixaban, 62 SOC) and included in the analysis across 33 sites in 12 countries over 4 years. Primary diagnosis was single ventricle in 72.9% of apixaban subjects and 76.2% of SOC. Overall 66.7% were post-Fontan. One apixaban subject had 2 primary safety events (incidence rate [IR] 1.8/100 person-years exposure [P-Y]) versus 3 subjects in SOC with 4 events (IR 6.8/100 P-Y). Serious adverse event rates were similar (apixaban 20.6% versus SOC 21.0%) but mild hematomas and epistaxis were reported more frequently with apixaban (6.3% versus 1.6%, and 15.9% versus 9.7%, respectively). There were no adjudicated TE events.

Conclusion(s): Thromboprophylaxis with apixaban was found to be safe and well tolerated in children with heart disease with numerically lower rate of major/CRNM bleeding versus SOC. PK/PD data will inform apixaban dosing for thromboprophylaxis in children.