pharmacokinetic, pharmacodynamic, safety, and efficacy study of rivaroxaban for thromboprophylaxis in pediatric participants 2 to 8 years of age after the fontan procedure

Conditions: Thrombosis

Summary: the purpose of this study is to characterize the single and multiple-dose pharmacokinetic (pk) and pharmacokinetic/pharmacodynamic (pk/ pd) profiles after oral rivaroxaban therapy administered to pediatric participants 2 to 8 years of age with single ventricle physiology who have completed the fontan procedure within 4 months prior to enrollment (part a) and to evaluate the safety and efficacy of rivaroxaban, administered twice daily (exposure matched to rivaroxaban 10 milligram \[mg\] once daily in adults) compared to acetylsalicylic acid (asa), given once daily (approximately 5 milligram per kilogram \[mg/kg\]) for thromboprophylaxis in pediatric participants 2 to 8 years of age with single ventricle physiology who have completed the fontan procedure within 4 months prior to enrollment.

part a: this part includes a 12-day initial pk, pd, and safety assessment period. participants in part a will not participate in part b. randomization in part b of this study will begin once the cumulative data from the initial pk, pd, and safety assessment period in part a are deemed acceptable by the independent data monitoring committee. part a of the study will consist of an up to 21-day screening period, a 12-day initial pk, pd, and safety assessment period, a 12-month open-label treatment period, and a 30-day follow-up phone contact. part b: participants will be randomly assigned to two treatment groups and randomization ratio will be 2:1 for rivaroxaban and asa. asa will be used as control. there will be an up to a 21-day screening period, a 12 month open-label treatment period and a 30-day follow-up phone contact.

Eligibility criteria:
inclusion criteria: * participant must be considered to be clinically stable by the investigator and able to tolerate oral or enteral administration of a suspension formulation and oral/enteral feedings * satisfactory initial post-fontan transthoracic echocardiographic screening as defined in the post-fontan echocardiographic examination research protocol * parent/legally acceptable representative must sign an informed consent form (icf) and child assent will also be provided, if applicable, according to local requirements exclusion criteria: * evidence of thrombosis, including those that are asymptomatic confirmed by post-fontan procedure transthoracic echocardiogram, or other imaging techniques, during the screening period of the study * history of gastrointestinal disease or surgery associated with clinically relevant impaired absorption * history of or signs/symptoms suggestive of protein-losing enteropathy * active bleeding or high risk for bleeding contraindicating antiplatelet or anticoagulant therapy, including a history of intracranial bleeding * platelet count less than (\<)50\*10\^9/liters (l) at screening * estimated glomerular filtration rate (egfr) \<30 milliliters per minute per 1.73 meter square (ml/min/1.73m\^2) * known clinically significant liver disease

Keywords: thromboembolism fontan procedure children