Clinical trial NCT02846532: Pharmacokinetic, Pharmacodynamic, Safety, and Efficacy Study of Rivaroxaban for Thromboprophylaxis in Pediatric Participants 2 to 8 Years of Age After the Fontan Procedure
Official title: A Prospective, Open-Label, Active-Controlled Study to Evaluate the Pharmacokinetics, Pharmacodynamics, Safety, and Efficacy of Rivaroxaban for Thromboprophylaxis in Pediatric Subjects 2 to 8 Years of Age After the Fontan Procedure
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Thrombosis
Keywords: Thromboembolism
Fontan Procedure
Children
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
Collaborators: name: Bayer
First posted: 2016-07-27
Enrollment: 112
Sex: ALL
Minimum age (years): 2
Maximum age (years): 8
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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

Primary outcomes:
measure: Percentage of Participants With Any Thrombotic Event (Venous or Arterial and Symptomatic or Asymptomatic)
timeFrame: Up to 12 months
measure: Plasma Concentration of Rivaroxaban at Day 1 (0.5-1.5 Hours Postdose)
timeFrame: Day 1: 0.5-1.5 hours postdose
measure: Plasma Concentration of Rivaroxaban at Day 1 (1.5-4 Hours Postdose)
timeFrame: Day 1: 1.5-4 hours postdose
measure: Plasma Concentration of Rivaroxaban at Day 4 (Up to 3 Hours Predose)
timeFrame: Day 4: Up to 3 hours predose
measure: Plasma Concentration of Rivaroxaban at Day 4 (0.5-1.5 Hours Postdose)
timeFrame: Day 4: 0.5-1.5 hours postdose
measure: Plasma Concentration of Rivaroxaban at Day 4 (1.5-4 Hours Postdose)
timeFrame: Day 4: 1.5-4 hours postdose
measure: Plasma Concentration of Rivaroxaban at Day 4 (6-8 Hours Postdose)
timeFrame: Day 4: 6-8 hours postdose
measure: Plasma Concentration of Rivaroxaban at Month 3 (Up to 3 Hours Predose)
timeFrame: Month 3: Up to 3 hours predose
measure: Plasma Concentration of Rivaroxaban at Month 3 (0.5-1.5 Hours Postdose)
timeFrame: Month 3: 0.5-1.5 hours postdose
measure: Plasma Concentration of Rivaroxaban at Month 3 (2.5-4 Hours Postdose)
timeFrame: Month 3: 2.5-4 hours postdose
measure: Percentage of Participants With Bleeding Events
timeFrame: Up to 12 months
measure: Absolute Prothrombin Time (PT) at Day 1 (0.5-1.5 Hours Postdose)
timeFrame: Day 1: 0.5-1.5 hours postdose
measure: Absolute PT at Day 1 (1.5-4 Hours Postdose)
timeFrame: Day 1: 1.5-4 hours postdose
measure: Absolute PT at Day 4 (Up to 3 Hours Predose)
timeFrame: Day 4: Up to 3 hours predose
measure: Absolute PT at Day 4 (0.5-1.5 Hours Postdose)
timeFrame: Day 4: 0.5-1.5 hours postdose
measure: Absolute PT at Day 4 (1.5-4 Hours Postdose)
timeFrame: Day 4: 1.5-4 hours postdose
measure: Absolute PT at Day 4 (6-8 Hours Postdose)
timeFrame: Day 4: 6-8 hours postdose
measure: Absolute PT at Month 3 (Up to 3 Hours Predose)
timeFrame: Month 3: Up to 3 hours predose
measure: Absolute PT at Month 3 (0.5-1.5 Hours Postdose)
timeFrame: Month 3: 0.5-1.5 hours postdose
measure: Absolute PT at Month 3 (2.5-4 Hours Postdose)
timeFrame: Month 3: 2.5-4 hours postdose
measure: Activated Partial Thromboplastin Time (aPTT) at Day 1 (0.5-1.5 Hours Postdose)
timeFrame: Day 1: 0.5-1.5 hours postdose
measure: aPTT at Day 1 (1.5-4 Hours Postdose)
timeFrame: Day 1: 1.5-4 hours postdose
measure: aPTT at Day 4 (Up to 3 Hours Predose)
timeFrame: Day 4: Up to 3 hours predose
measure: aPTT at Day 4 (0.5-1.5 Hours Postdose)
timeFrame: Day 4: 0.5-1.5 hours postdose
measure: aPTT at Day 4 (1.5-4 Hours Postdose)
timeFrame: Day 4: 1.5-4 hours postdose
measure: aPTT at Day 4 (6-8 Hours Postdose)
timeFrame: Day 4: 6-8 hours postdose
measure: aPTT at Month 3 (Up to 3 Hours Predose)
timeFrame: Month 3: Up to 3 hours predose
measure: aPTT at Month 3 (0.5-1.5 Hours Postdose)
timeFrame: Month 3: 0.5-1.5 hours postdose
measure: aPTT at Month 3 (2.5-4 Hours Postdose)
timeFrame: Month 3: 2.5-4 hours postdose
measure: Anti-FXa at Day 1 (0.5-1.5 Hours Postdose)
timeFrame: Day 1: 0.5-1.5 hours postdose
measure: Anti-FXa at Day 1 (1.5-4 Hours Postdose)
timeFrame: Day 1: 1.5-4 hours postdose
measure: Anti-FXa at Day 4 (6-8 Hours Postdose)
timeFrame: Day 4: 6-8 hours postdose
measure: Anti-FXa at Month 3 (Up to 3 Hours Predose)
timeFrame: Month 3: Up to 3 hours predose
measure: Anti-FXa at Month 3 (0.5-1.5 Hours Postdose)
timeFrame: Month 3: 0.5-1.5 hours postdose
measure: Anti-FXa at Month 3 (2.5-4 Hours Postdose)
timeFrame: Month 3: 2.5-4 hours postdose
Secondary outcomes:
measure: Percentage of Participants With Treatment-emergent Adverse Events (TEAEs)
timeFrame: Up to 12 months
Other outcomes:
Locations:
city: Los Angeles
country: United States
state: California
city: Gainesville
country: United States
state: Florida
city: Oak Lawn
country: United States
state: Illinois
city: Indianapolis
country: United States
state: Indiana
city: Iowa City
country: United States
state: Iowa
city: Baltimore
country: United States
state: Maryland
city: Boston
country: United States
state: Massachusetts
city: Minneapolis
country: United States
state: Minnesota
city: Omaha
country: United States
state: Nebraska
city: Durham
country: United States
state: North Carolina
city: Cincinnati
country: United States
state: Ohio
city: Hershey
country: United States
state: Pennsylvania
city: Philadelphia
country: United States
state: Pennsylvania
city: Memphis
country: United States
state: Tennessee
city: Houston
country: United States
state: Texas
city: Salt Lake City
country: United States
state: Utah
city: Milwaukee
country: United States
state: Wisconsin
city: Buenos Aires
country: Argentina
city: Cordoba
country: Argentina
city: Brussel
country: Belgium
city: Gent
country: Belgium
city: Leuven
country: Belgium
city: Curitiba
country: Brazil
city: Porto Alegre
country: Brazil
city: Sao Paulo
country: Brazil
city: Vancouver
country: Canada
state: British Columbia
city: Toronto
country: Canada
state: Ontario
city: Montreal
country: Canada
state: Quebec
city: Fukuoka
country: Japan
city: Kitakyushu-shi
country: Japan
city: Setagaya Ku
country: Japan
city: Shizuoka-shi
country: Japan
city: Kuala Lumpur
country: Malaysia
city: Mexico
country: Mexico
city: Leiden
country: Netherlands
city: Rotterdam
country: Netherlands
city: Utrecht
country: Netherlands
city: A Coruña
country: Spain
city: Barcelona
country: Spain
city: Bilbao
country: Spain
city: Madrid
country: Spain
city: Valencia
country: Spain
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References:
citation: 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.