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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02846532
Recruitment Status : Completed
First Posted : July 27, 2016
Last Update Posted : July 16, 2021
Information provided by (Responsible Party):
Janssen Research & Development, LLC

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.

Condition or disease Intervention/treatment Phase
Thrombosis Drug: Rivaroxaban Drug: Acetylsalicylic Acid Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 112 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
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
Actual Study Start Date : November 16, 2016
Actual Primary Completion Date : July 16, 2020
Actual Study Completion Date : July 16, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Blood Clots

Arm Intervention/treatment
Experimental: Rivaroxaban Drug: 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.

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

Primary Outcome Measures :
  1. Maximum Observed Plasma Concentration (Cmax) [ Time Frame: Up to Month 12 ]
    The Cmax is the maximum observed Plasma concentration.

  2. Area Under the Analyte ConcentrationTime Curve From Time 0 to 24 Hours (AUC24) [ Time Frame: Up to Month 12 ]
    The AUC24 is the area under the plasma concentration-time curve from time 0 to 24 hours.

  3. Maximum Plasma Concentration (Cmax,ss) at Steady State [ Time Frame: Up to Month 12 ]
    The Cmax,ss is the maximum observed plasma concentration at steady state.

  4. Minimum Plasma Concentration (Cmin,ss) at Steady State [ Time Frame: Up to Month 12 ]
    The Cmin,ss is the minimum observed plasma concentration at steady state.

  5. Absolute Prothrombin Time (PT) [ Time Frame: Up to Month 12 ]
    Absolute prothrombin time (PT) will be assessed as pharmacodynamic parameter.

  6. Activated Partial Thromboplastin Time (aPTT) [ Time Frame: Up to Month 12 ]
    Activated partial thromboplastin time (aPTT) will be assessed as pharmacodynamic parameter.

  7. Anti-Factor Xa (FXa) [ Time Frame: Up to Month 12 ]
    Anti-factor Xa (FXa) will be assessed as pharmacodynamic parameter.

  8. Number of Participants With Major Bleeding Events [ Time Frame: Up to Month 12 ]
    Major bleeding is defined as overt bleeding and associated with a fall in hemoglobin of 2 gram per deciliter (g/dL) or more; or leading to a transfusion of the equivalent of 2 or more units of packed red blood cells or whole blood in adults; or occurring in a critical site: intracranial, intraspinal, intraocular, pericardial, intra-articular, intramuscular with compartment syndrome, retroperitoneal; or contributing to death.

  9. Number of Participants With Incidence of Thrombotic Events [ Time Frame: Up to Month 12 ]
    Thrombotic event is defined as the appearance of a new thrombotic burden within the cardiovascular system on either routine surveillance or clinically indicated imaging, or the occurrence of a clinical event known to be strongly associated with thrombus (such as cardioembolic stroke, pulmonary embolism).

Secondary Outcome Measures :
  1. Number of Participants With Adverse Events as a Measure of Safety and Tolerability [ Time Frame: For the duration of the study, average 13 months ]
  2. Number of Participants With Clinically Relevant Non-Major Bleeding Events [ Time Frame: Up to Month 12 ]
    Clinically relevant non-major bleeding is defined as overt bleeding not meeting the criteria for major bleeding but associated with: medical intervention, or unscheduled contact (visit or telephone call) with a physician, or (Temporary) cessation of study treatment, or discomfort for the subject such as pain, or impairment of activities of daily life (such as loss of school days or hospitalization).

  3. Number of Participants With Trivial (Minimal) Bleeding [ Time Frame: Up to Month 12 ]
    Trivial (minimal) bleeding is defined as any other overt bleeding event that does not meet criteria for clinically relevant non major bleeding.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   2 Years to 8 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02846532

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United States, California
Los Angeles, California, United States
United States, Florida
Gainesville, Florida, United States
United States, Illinois
Oak Lawn, Illinois, United States
United States, Indiana
Indianapolis, Indiana, United States
United States, Iowa
Iowa City, Iowa, United States
United States, Maryland
Baltimore, Maryland, United States
United States, Massachusetts
Boston, Massachusetts, United States
United States, Minnesota
Minneapolis, Minnesota, United States
United States, Nebraska
Omaha, Nebraska, United States
United States, North Carolina
Durham, North Carolina, United States
United States, Ohio
Cincinnati, Ohio, United States
United States, Pennsylvania
Hershey, Pennsylvania, United States
Philadelphia, Pennsylvania, United States
United States, Tennessee
Memphis, Tennessee, United States
United States, Texas
Houston, Texas, United States
United States, Utah
Salt Lake City, Utah, United States
United States, Wisconsin
Milwaukee, Wisconsin, United States
Buenos Aires, Argentina
Cordoba, Argentina
Brussel, Belgium
Gent, Belgium
Leuven, Belgium
Curitiba, Brazil
Porto Alegre, Brazil
São Paulo, Brazil
Canada, British Columbia
Vancouver, British Columbia, Canada
Canada, Ontario
Toronto, Ontario, Canada
Canada, Quebec
Montreal, Quebec, Canada
Fukuoka, Japan
Kitakyushu-shi,, Japan
Setagaya-ku, Japan
Shizuoka-shi, Shizuoka, Japan
Kuala Lumpur, Malaysia
Mexico, Mexico
Leiden, Netherlands
Rotterdam, Netherlands
Utrecht, Netherlands
A Coruña, Spain
Barcelona, Spain
Bilbao, Spain
Madrid, Spain
Valencia, Spain
Sponsors and Collaborators
Janssen Research & Development, LLC
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Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC
Additional Information:
Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Janssen Research & Development, LLC Identifier: NCT02846532    
Other Study ID Numbers: CR108075
39039039CHD3001 ( Other Identifier: Janssen Research & Development, LLC )
2015-002610-76 ( EudraCT Number )
First Posted: July 27, 2016    Key Record Dates
Last Update Posted: July 16, 2021
Last Verified: July 2021

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Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Janssen Research & Development, LLC:
Fontan Procedure
Additional relevant MeSH terms:
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Embolism and Thrombosis
Vascular Diseases
Cardiovascular Diseases
Factor Xa Inhibitors
Serine Proteinase Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antirheumatic Agents
Fibrinolytic Agents
Fibrin Modulating Agents
Platelet Aggregation Inhibitors
Cyclooxygenase Inhibitors