Rivaroxaban, a direct Factor Xa inhibitor, versus acetylsalicylic acid as thromboprophylaxis in children post-Fontan procedure: Rationale and design of a prospective, randomized trial (the UNIVERSE study)

Am Heart J. 2019 Jul:213:97-104. doi: 10.1016/j.ahj.2019.04.009. Epub 2019 May 1.

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.

Publication types

  • Clinical Trial Protocol
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aspirin / administration & dosage*
  • Aspirin / pharmacokinetics
  • Child
  • Child, Preschool
  • Factor Xa Inhibitors / administration & dosage*
  • Factor Xa Inhibitors / pharmacokinetics
  • Female
  • Fibrinolytic Agents / administration & dosage*
  • Fibrinolytic Agents / pharmacokinetics
  • Fontan Procedure / adverse effects*
  • Humans
  • Male
  • Multicenter Studies as Topic
  • Postoperative Complications / prevention & control*
  • Prospective Studies
  • Randomized Controlled Trials as Topic*
  • Rivaroxaban / administration & dosage*
  • Rivaroxaban / pharmacokinetics
  • Thrombosis / prevention & control*

Substances

  • Factor Xa Inhibitors
  • Fibrinolytic Agents
  • Rivaroxaban
  • Aspirin