Liza Miriam Pina1, Xiangwen Dong1, Liping Zhang1, Mahesh N Samtani1, Alan D Michelson2, Henri Justino3, Damien Bonnet4, Kevin C Harris5, John Jefferies6, Brian W McCrindle7, Jennifer S Li8. 1. Janssen Research and Development, LLC., Raritan, NJ 08869. 2. Boston Children's Hospital, Boston, MA 02115. 3. Texas Children's Hospital, Houston, TX 77030. 4. Hôpital Necker-Enfants Malades, Paris 15, France. 5. Children's Heart Centre, BC Children's Hospital, Vancouver, BC V6H 3N1, Canada. 6. The Heart Institute, Cincinnati Children's Hospital Medical Centre, Cincinnati, OH 45229. 7. The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada. 8. Duke University Medical Center, Durham, NC 27710. Electronic address: jennifer.li@duke.edu.
Abstract
BACKGROUND: The Fontan procedure is the final step of the 3-stage palliative procedure commonly performed in children with single ventricle physiology. Thrombosis remains an important complication in children after this procedure. To date, guideline recommendations for the type and duration of thromboprophylaxis after Fontan surgery are mainly based on extrapolation of knowledge gained from adults at risk for thrombosis in other clinical settings. Warfarin is being used off-label, and because of its multiple interactions with other drugs and food, a new alternative is highly desirable. Rivaroxaban, a direct Factor Xa inhibitor with a predictable pharmacokinetic profile, is a candidate to address this medical need. STUDY DESIGN: The UNIVERSE study is a prospective, open-label, active-controlled, multicenter study in children 2 to 8 years of age who have single ventricle physiology and had the Fontan procedure within the 4 months preceding enrollment. This study consists of 2 parts. In Part A, rivaroxaban pharmacokinetics, pharmacodynamics, safety, and tolerability are assessed to validate the pediatric dosing selected. In Part B, safety and efficacy of rivaroxaban versus acetylsalicylic acid are evaluated for thromboprophylaxis in children post-Fontan procedure. Children in each part will receive study drug for 12 months. Part A has been completed with 12 children enrolled. Enrollment into Part B is currently ongoing. CONCLUSIONS: The UNIVERSE study aims to provide dosing, pharmacokinetics/pharmacodynamics, safety, and efficacy information on the use of rivaroxaban, an oral anticoagulant, versus acetylsalicylic acid, an antiplatelet agent, in children with single ventricle physiology after the Fontan procedure.
RCT Entities:
BACKGROUND: The Fontan procedure is the final step of the 3-stage palliative procedure commonly performed in children with single ventricle physiology. Thrombosis remains an important complication in children after this procedure. To date, guideline recommendations for the type and duration of thromboprophylaxis after Fontan surgery are mainly based on extrapolation of knowledge gained from adults at risk for thrombosis in other clinical settings. Warfarin is being used off-label, and because of its multiple interactions with other drugs and food, a new alternative is highly desirable. Rivaroxaban, a direct Factor Xa inhibitor with a predictable pharmacokinetic profile, is a candidate to address this medical need. STUDY DESIGN: The UNIVERSE study is a prospective, open-label, active-controlled, multicenter study in children 2 to 8 years of age who have single ventricle physiology and had the Fontan procedure within the 4 months preceding enrollment. This study consists of 2 parts. In Part A, rivaroxaban pharmacokinetics, pharmacodynamics, safety, and tolerability are assessed to validate the pediatric dosing selected. In Part B, safety and efficacy of rivaroxaban versus acetylsalicylic acid are evaluated for thromboprophylaxis in children post-Fontan procedure. Children in each part will receive study drug for 12 months. Part A has been completed with 12 children enrolled. Enrollment into Part B is currently ongoing. CONCLUSIONS: The UNIVERSE study aims to provide dosing, pharmacokinetics/pharmacodynamics, safety, and efficacy information on the use of rivaroxaban, an oral anticoagulant, versus acetylsalicylic acid, an antiplatelet agent, in children with single ventricle physiology after the Fontan procedure.
Authors: John M Kelly; Gabriel J M Mirhaidari; Yu-Chun Chang; Toshiharu Shinoka; Christopher K Breuer; Andrew R Yates; Kan N Hor Journal: Pediatr Cardiol Date: 2020-11-08 Impact factor: 1.655
Authors: Brian W McCrindle; Alan D Michelson; Andrew H Van Bergen; Estela Suzana Horowitz; Juan Pablo Sandoval; Henri Justino; Kevin C Harris; John L Jefferies; Liza Miriam Pina; Colleen Peluso; Kimberly Nessel; Wentao Lu; Jennifer S Li Journal: J Am Heart Assoc Date: 2021-09-24 Impact factor: 5.501
Authors: Suelyn Van Den Helm; Christopher Noel Sparks; Vera Ignjatovic; Paul Monagle; Chantal Attard Journal: Front Pediatr Date: 2022-03-28 Impact factor: 3.418
Authors: Peijuan Zhu; Stefan Willmann; Wangda Zhou; Haitao Yang; Alan D Michelson; Brian W McCrindle; Jennifer S Li; Kevin C Harris; Liza Miriam Pina; Traci Weber; Kimberly Nessel; Lawrence J Lesko; Dagmar Kubitza; Peter Zannikos Journal: J Clin Pharmacol Date: 2022-01-09 Impact factor: 2.860