Phase 3
N=112
Pharmacokinetic, Pharmacodynamic, Safety, and Efficacy Study of Rivaroxaban for Thromboprophylaxis in Pediatric Participants 2 to 8 Years of Age After the Fontan Procedure
Thrombosis
Bottom Line
View on ClinicalTrials.gov: NCT02846532 ↗Enrolled (actual)
112
Serious AEs
30.0%
Results posted
Mar 2022
Primary outcome: Primary: Percentage of Participants With Any Thrombotic Event (Venous or Arterial and Symptomatic or Asymptomatic) — 8.3; 1.6; 8.8; 0 percentage of participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Rivaroxaban (Drug); Acetylsalicylic Acid (Drug)
- Age
- Pediatric · 2+ yrs
- Sex
- All
- Sponsor
- Janssen Research & Development, LLC
- Primary completion
- Jul 2020
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage of Participants With Any Thrombotic Event (Venous or Arterial and Symptomatic or Asymptomatic) |
8.3; 1.6; 8.8; 0; 0; 2.9 | — |
| PRIMARY Plasma Concentration of Rivaroxaban at Day 1 (0.5-1.5 Hours Postdose) |
46.69; 92.86 | — |
| PRIMARY Plasma Concentration of Rivaroxaban at Day 1 (1.5-4 Hours Postdose) |
86.62; 103.61 | — |
| PRIMARY Plasma Concentration of Rivaroxaban at Day 4 (Up to 3 Hours Predose) |
36.58 | — |
| PRIMARY Plasma Concentration of Rivaroxaban at Day 4 (0.5-1.5 Hours Postdose) |
107.58 | — |
| PRIMARY Plasma Concentration of Rivaroxaban at Day 4 (1.5-4 Hours Postdose) |
147.18 | — |
| PRIMARY Plasma Concentration of Rivaroxaban at Day 4 (6-8 Hours Postdose) |
66.81 | — |
| PRIMARY Plasma Concentration of Rivaroxaban at Month 3 (Up to 3 Hours Predose) |
38.23; 29.41 | — |
| PRIMARY Plasma Concentration of Rivaroxaban at Month 3 (0.5-1.5 Hours Postdose) |
86.25; 94.12 | — |
| PRIMARY Plasma Concentration of Rivaroxaban at Month 3 (2.5-4 Hours Postdose) |
96.67; 102.99 | — |
| PRIMARY Percentage of Participants With Bleeding Events |
33.3; 35.9; 41.2; 0; 1.6; 0 | — |
| PRIMARY Absolute Prothrombin Time (PT) at Day 1 (0.5-1.5 Hours Postdose) |
15.46; 18.02 | — |
| PRIMARY Absolute PT at Day 1 (1.5-4 Hours Postdose) |
16.58; 18.76 | — |
| PRIMARY Absolute PT at Day 4 (Up to 3 Hours Predose) |
15.21 | — |
| PRIMARY Absolute PT at Day 4 (0.5-1.5 Hours Postdose) |
17.95 | — |
| PRIMARY Absolute PT at Day 4 (1.5-4 Hours Postdose) |
18.73 | — |
| PRIMARY Absolute PT at Day 4 (6-8 Hours Postdose) |
16.13 | — |
| PRIMARY Absolute PT at Month 3 (Up to 3 Hours Predose) |
17.59; 16.45 | — |
| PRIMARY Absolute PT at Month 3 (0.5-1.5 Hours Postdose) |
20.13; 18.89 | — |
| PRIMARY Absolute PT at Month 3 (2.5-4 Hours Postdose) |
19.14; 19.69 | — |
| PRIMARY Activated Partial Thromboplastin Time (aPTT) at Day 1 (0.5-1.5 Hours Postdose) |
31.4; 30.69 | — |
| PRIMARY aPTT at Day 1 (1.5-4 Hours Postdose) |
32.83; 30.25 | — |
| PRIMARY aPTT at Day 4 (Up to 3 Hours Predose) |
33.08 | — |
| PRIMARY aPTT at Day 4 (0.5-1.5 Hours Postdose) |
36.17 | — |
| PRIMARY aPTT at Day 4 (1.5-4 Hours Postdose) |
37.58 | — |
| PRIMARY aPTT at Day 4 (6-8 Hours Postdose) |
32.83 | — |
| PRIMARY aPTT at Month 3 (Up to 3 Hours Predose) |
25.36; 28.70 | — |
| PRIMARY aPTT at Month 3 (0.5-1.5 Hours Postdose) |
26.60; 31.15 | — |
| PRIMARY aPTT at Month 3 (2.5-4 Hours Postdose) |
26.74; 31.67 | — |
| PRIMARY Anti-FXa at Day 1 (0.5-1.5 Hours Postdose) |
66.93; 99.46 | — |
| PRIMARY Anti-FXa at Day 1 (1.5-4 Hours Postdose) |
74.06; 104.57 | — |
| PRIMARY Anti-FXa at Day 4 (6-8 Hours Postdose) |
74.21 | — |
| PRIMARY Anti-FXa at Month 3 (Up to 3 Hours Predose) |
60.51; 53.41 | — |
| PRIMARY Anti-FXa at Month 3 (0.5-1.5 Hours Postdose) |
110.90 | — |
| PRIMARY Anti-FXa at Month 3 (2.5-4 Hours Postdose) |
93.48 | — |
| SECONDARY Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) |
91.7; 85.9; 85.3 | — |
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.
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
Data sourced from ClinicalTrials.gov (NCT02846532). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.