thromboprophylaxis MedDRA version: 19.0 Level: LLT Classification code 10040729 Term: Single ventricle System Organ Class: 100000004850
Conditions
Interventions
Product Name: Xarelto
Product Code: JNJ-39039039
BAY 59-7939
Pharmaceutical Form: Granules for oral solution
INN or Proposed INN: RIVAROXABAN
CAS Number: 366789-02-8
Current Sponsor code: JNJ-39039039
BAY 59-7939
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 1-
Trade Name: Aspirin
Product Name: acetylsalicylic acid
Pharmaceutical Form: Tablet
INN
Sponsors
Janssen-Cilag International N.V
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Boys or girls 2 to 8 years of age with single ventricle physiology and who have completed the initial Fontan procedure within 4 months prior to enrollment 2. Considered to be clinically stable by the investigator and able to tolerate oral or enteral administration of a suspension formulation and oral/enteral feedings 3. Satisfactory initial post-Fontan transthoracic echocardiographic screening as defined in the Post-Fontan Echocardiographic Examination Research Protocol 4. Parent/legally acceptable representative must sign an informed consent form (ICF) and child assent will also be provided, if applicable, according to local requirements. Are the trial subjects under 18? yes Number of subjects for this age range: 100 F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. 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 2. History of gastrointestinal disease or surgery associated with clinically relevant impaired absorption 3. History of or signs/symptoms suggestive of protein-losing enteropathy 4. Active bleeding or high risk for bleeding contraindicating antiplatelet or anticoagulant therapy, including a history of intracranial bleeding 5. Indication for anticoagulant or antiplatelet therapy other than current study, however: - A subject who has received VKA after the Fontan procedure may be eligible provided that the subject has discontinued VKA before the screening visit. Baseline laboratory samples must be obtained at least 7 days after the last dose of VKA. - A subject who is receiving ASA at the time of the screening visit may be eligible and may continue on ASA provided the last dose is taken at least 24 hours prior to the first dose of study drug. 6. Platelet count <50 x 10^9/L at screening. 7. Creatinine clearance (CrCl) <30 mL/min/1.73m2. 8. Known clinically significant liver disease.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Part A To characterize the single- and multiple-dose PK and PK/ PD profiles after oral rivaroxaban therapy administered to pediatric subjects 2 to 8 years of age with single ventricle physiology who have completed the Fontan procedure within 4 months prior to enrollment. Part B To evaluate the safety and efficacy of rivaroxaban, administered twice daily (exposure matched to rivaroxaban 10 mg once daily in adults) compared to ASA, given once daily (approximately 5 mg/kg) for thromboprophylaxis in pediatric subjects 2 to 8 years of age with single ventricle physiology who have completed the Fontan procedure within 4 months prior to enrollment.;Secondary Objective: Part A To assess the safety and tolerability of rivaroxaban treatment. Part B To further characterize the PK and PK/PD profiles of rivaroxaban.;Primary end point(s): Part A: PK and PD Parameters: PT, aPTT and anti-FXa activity against Rivaroxaban plasma concentration. PK: AUC (O-24), Cmax after single dose and AUC (0-24), Cmax and Cmin at steady state Part B: Efficacy: Thrombotic events (venous or arterial), 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). Safety: major bleeding events as defined by ISTH ;Timepoint(s) of evaluation of this end point: Part A: Day 1, 4, Month 3, 12 Part B: Ongoing throughout the study as well as at pre-defined time points (Day 12, Months 3, 6 and 12) from enrollment until final follow-up phone call | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Part A: Efficacy: Thrombotic events (venous or arterial), 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). Any death Safety: major bleeding events, Clinically relevant non-major bleeding events and trivial (minimal) bleeding as defined by ISTH; other adverse events and clinical laboratory test values (CBC, CrCl, liver function tests, and PT and aPTT). Part B: PK/PD Parameters: PT, aPTT and anti-FXa activity against Rivaroxaban plasma concentration. PK: AUC (O-24), Cmax after single dose and AUC (0-24), Cmax and Cmin at steady state Safety: Clinically relevant non-major bleeding events and trivial (minimal) bleeding as defined by ISTH; any death, other adverse events and clinical laboratory test values(CBC, CrCl, liver function tests, and PT and aPTT) . ;Timepoint(s) of evaluation of this end point: Part A: Ongoing throughout the study as well as at pre-defined time points (Day 12, Months 3, 6 and 12) from enrollment until final follow-up examination Part B: Day 1, Month 3, Month 12 | — |
Countries
Argentina, Australia, Belgium, Brazil, Canada, China, France, Japan, Korea, Republic of, Malaysia, Mexico, Netherlands, Spain, Thailand, United Kingdom, United States
Contacts
Public ContactLiza Miriam Pina, MD
Janssen Research and Development, LLC
Outcome results
None listed