Pharmacokinetic, Pharmacodynamic, Safety, and Efficacy Study of Rivaroxaban for Thromboprophylaxis in Pediatric Participants 2 to 8 Years of Age After the Fontan Procedure

NCT ID: NCT02846532

Last Updated: 2025-03-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 112 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-11-16
• Study Completion Date: 2020-07-16

Brief 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.

Detailed Description

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.

Conditions

Thrombosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Rivaroxaban

Group Type: EXPERIMENTAL

Rivaroxaban

Intervention Type: DRUG

Participants will receive oral suspension containing rivaroxaban 1 milligram per milliliter (mg/ml) twice daily in Part A and Part B. Following total daily doses of Rivaroxaban will be administered based on the weight of the participants: 7 to \<8 kilogram (kg) will receive 2.2 milligram (mg); 8 to \<10 kg will receive 3.2 mg; 10 to\<12 kg will receive 3.4 mg; 12 to \<20 will receive 4.0 mg and 20 to \<30 will receive 5.0 mg.

Acetylsalicylic Acid

Group Type: EXPERIMENTAL

Acetylsalicylic Acid

Intervention Type: DRUG

Participants will receive 5 milligram per kilogram (mg/kg) of acetylsalicylic acid once daily up to 12 months in Part B.

Interventions

Rivaroxaban

Participants will receive oral suspension containing rivaroxaban 1 milligram per milliliter (mg/ml) twice daily in Part A and Part B. Following total daily doses of Rivaroxaban will be administered based on the weight of the participants: 7 to \<8 kilogram (kg) will receive 2.2 milligram (mg); 8 to \<10 kg will receive 3.2 mg; 10 to\<12 kg will receive 3.4 mg; 12 to \<20 will receive 4.0 mg and 20 to \<30 will receive 5.0 mg.

Intervention Type: DRUG

Acetylsalicylic Acid

Participants will receive 5 milligram per kilogram (mg/kg) of acetylsalicylic acid once daily up to 12 months in Part B.

Intervention Type: DRUG

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

• Minimum Eligible Age: 2 Years
• Maximum Eligible Age: 8 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Janssen Research & Development, LLC

INDUSTRY

Sponsor Role: lead

Bayer

INDUSTRY

Sponsor Role: collaborator

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Janssen Research & Development, LLC Clinical Trial

Role: STUDY_DIRECTOR

Janssen Research & Development, LLC

Locations

Los Angeles, California, United States

Gainesville, Florida, United States

Oak Lawn, Illinois, United States

Indianapolis, Indiana, United States

Iowa City, Iowa, United States

Baltimore, Maryland, United States

Boston, Massachusetts, United States

Minneapolis, Minnesota, United States

Omaha, Nebraska, United States

Durham, North Carolina, United States

Cincinnati, Ohio, United States

Hershey, Pennsylvania, United States

Philadelphia, Pennsylvania, United States

Memphis, Tennessee, United States

Houston, Texas, United States

Salt Lake City, Utah, United States

Milwaukee, Wisconsin, United States

Buenos Aires, , Argentina

Córdoba, , Argentina

Brussels, , Belgium

Ghent, , Belgium

Leuven, , Belgium

Curitiba, , Brazil

Porto Alegre, , Brazil

São Paulo, , Brazil

Vancouver, British Columbia, Canada

Toronto, Ontario, Canada

Montreal, Quebec, Canada

Fukuoka, , Japan

Kitakyushu-shi, , Japan

Setagaya Ku, , Japan

Shizuoka, , Japan

Kuala Lumpur, , Malaysia

México, , Mexico

Leiden, , Netherlands

Rotterdam, , Netherlands

Utrecht, , Netherlands

A Coruña, , Spain

Barcelona, , Spain

Bilbao, , Spain

Madrid, , Spain

Valencia, , Spain

Countries

United States; Argentina; Belgium; Brazil; Canada; Japan; Malaysia; Mexico; Netherlands; Spain

References

McCrindle BW, Michelson AD, Van Bergen AH, Suzana Horowitz E, Pablo Sandoval J, Justino H, Harris KC, Jefferies JL, Miriam Pina L, Peluso C, Nessel K, Lu W, Li JS; UNIVERSE Study Investigators *. Thromboprophylaxis for Children Post-Fontan Procedure: Insights From the UNIVERSE Study. J Am Heart Assoc. 2021 Nov 16;10(22):e021765. doi: 10.1161/JAHA.120.021765. Epub 2021 Sep 24.

Reference Type: DERIVED

PMID: 34558312 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

https://filehosting-v2.pharmacm.com/api/Attachment/Download?tenantId=80217051&amp;parentIdentifier=CR108075&amp;attachmentIdentifier=ecc7606d-69c9-4747-8c64-2f0ad414eacd&amp;fileName=2015-002610-76-_Receipt.png&amp;versionIdentifier=

ERF update upload receipt

Other Identifiers

39039039CHD3001

Identifier Type: OTHER

Identifier Source: secondary_id

2015-002610-76

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CR108075

Identifier Type: -

Identifier Source: org_study_id