Phase 3
Completed N=500
EINSTEIN Junior: Oral Rivaroxaban in Children With Venous Thrombosis
Source: ClinicalTrials.gov NCT02234843 ↗Enrolled (actual)
500
Serious AEs
23.0%
Results posted
Apr 2020
Primary outcomePrimary: Incidence Rates of All Symptomatic Recurrent Venous Thromboembolism During the Main Treatment Period — 1.2; 3.0 Percentage of participants — p=0.1509
◆ Published Evidence
Highly cited
314citations · ~52 / year
Rivaroxaban compared with standard anticoagulants for the treatment of acute venous thromboembolism in children: a randomised, controlled, phase 3 trial.
Summary
The purpose of this study is to evaluate comparative efficacy and safety of rivaroxaban to standard of care in children with acute venous thromboembolism.
Linked Publications (5)
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Rivaroxaban compared with standard anticoagulants for the treatment of acute venous thromboembolism in children: a randomised, controlled, phase 3 trial.
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Safety and efficacy of rivaroxaban in pediatric cerebral venous thrombosis (EINSTEIN-Jr CVT).
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Bodyweight-adjusted rivaroxaban for children with venous thromboembolism (EINSTEIN-Jr): results from three multicentre, single-arm, phase 2 studies.
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Safety and efficacy of anticoagulant therapy in pediatric catheter-related venous thrombosis (EINSTEIN-Jr CVC-VTE).
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Anticoagulation in pediatric cancer-associated venous thromboembolism: a subgroup analysis of EINSTEIN-Jr.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Incidence Rates of All Symptomatic Recurrent Venous Thromboembolism During the Main Treatment Period |
2.2; 0.0; 0.0; 0.0; 0.0; 3.3 | — |
| PRIMARY Incidence Rates of All Symptomatic Recurrent Venous Thromboembolism During the Main Treatment Period |
2.2; 0.0; 0.0; 0.0; 0.0; 3.3 | — |
| PRIMARY Incidence Rates of All Symptomatic Recurrent Venous Thromboembolism During Extended Treatment Period |
0.0; 2.2; 0.0; 0.0; 0.0; 0.0 | — |
| PRIMARY Number of Subjects With the Composite of All Symptomatic Recurrent Venous Thromboembolism During the 30 Days Post-study Treatment Period (i.e. >2 and ≤ 30 Days After Stop of Study Medication) |
0; 2; 0; 0; 0; 0 | — |
| PRIMARY Incidence Rates of the Composite of Treatment Emergent Overt Major Bleeding and Clinically Relevant Non-major (CRNM) Bleeding During Main Treatment Period |
1.7; 3.0; 6.5; 4.8; 6.7; 2.2 | — |
| PRIMARY Incidence Rates of the Composite of Treatment Emergent Overt Major Bleeding and Clinically Relevant Non-major (CRNM) Bleeding During Extended Treatment Period |
1.1; 0.0; 0.0; 0.0; 0.0; 0.0 | — |
| SECONDARY Incidence Rates of the Composite of All Symptomatic Recurrent Venous Thromboembolism and Asymptomatic Deterioration in Thrombotic Burden on Repeat Imaging During the Main Treatment Period |
2.2; 0.0; 2.1; 0.0; 0.0; 4.3 | — |
| SECONDARY AUC(0-24)ss in Plasma |
2120; 1960; 2380; 1840; 1590 | — |
| SECONDARY Cmax,ss in Plasma |
237; 184; 182; 136; 119 | — |
| SECONDARY Ctrough,ss in Plasma |
20.7; 21.4; 31.6; 22.9; 18.5 | — |
| SECONDARY Prothrombin Time (PT) Ratios to Baseline: Rivaroxaban Administered Once Daily (Suspension and Tablet) in the Age Group 12-<18 Years |
1.29; 1.57; 1.52 | — |
| SECONDARY Prothrombin Time (PT) Ratios to Baseline: Rivaroxaban Administered Once Daily (Suspension and Tablet) in the Age Group 6-<12 Years |
1.46; 1.67; 1.52 | — |
| SECONDARY Prothrombin Time (PT) Ratios to Baseline: Rivaroxaban Administered Twice Daily (Suspension and Tablet) in the Age Group 6-<12 Years |
1.17; 1.26; 1.21 | — |
| SECONDARY Prothrombin Time (PT) Ratios to Baseline: Rivaroxaban Administered Twice Daily (Suspension) in the Age Group 2-<6 Years |
0.99; 1.36; 1.33 | — |
| SECONDARY Prothrombin Time (PT) Ratios to Baseline: Rivaroxaban Administered Twice Daily (Suspension) in the Age Group 0.5-<2 Years |
1.41; 1.05 | — |
| SECONDARY Prothrombin Time (PT) Ratios to Baseline: Rivaroxaban Administered Three Times Daily (Suspension) in the Age Group 2-<6 Years |
1.87; 1.32 | — |
| SECONDARY Prothrombin Time (PT) Ratios to Baseline: Rivaroxaban Administered Three Times Daily (Suspension) in the Age Group 0.5-<2 Years |
1.25; 2.00 | — |
| SECONDARY Prothrombin Time (PT) Ratios to Baseline: Rivaroxaban Administered Three Times Daily (Suspension) in the Age Group Birth-<0.5 Years |
1.35; 1.45 | — |
| SECONDARY Activated Partial Thromboplastin Time (aPTT) Ratios to Baseline: Rivaroxaban Administered Once Daily (Suspension and Tablet) in the Age Group 12-<18 Years |
1.17; 1.38; 1.33 | — |
| SECONDARY Activated Partial Thromboplastin Time (aPTT) Ratios to Baseline: Rivaroxaban Administered Once Daily (Suspension and Tablet) in the Age Group 6-<12 Years |
1.27; 1.39; 1.24 | — |
| SECONDARY Activated Partial Thromboplastin Time (aPTT) Ratios to Baseline: Rivaroxaban Administered Twice Daily (Suspension and Tablet) in the Age Group 6-<12 Years |
1.11; 1.15; 1.18 | — |
| SECONDARY Activated Partial Thromboplastin Time (aPTT) Ratios to Baseline: Rivaroxaban Administered Twice Daily (Suspension) in the Age Group 2-<6 Years |
0.90; 1.29; 1.23 | — |
| SECONDARY Activated Partial Thromboplastin Time (aPTT) Ratios to Baseline: Rivaroxaban Administered Twice Daily (Suspension) in the Age Group 0.5-<2 Years |
1.13; 1.10 | — |
| SECONDARY Activated Partial Thromboplastin Time (aPTT) Ratios to Baseline: Rivaroxaban Administered Three Times Daily (Suspension) in the Age Group 2-<6 Years |
1.50; 1.13 | — |
| SECONDARY Activated Partial Thromboplastin Time (aPTT) Ratios to Baseline: Rivaroxaban Administered Three Times Daily (Suspension) in the Age Group 0.5-<2 Years |
1.20; 1.10 | — |
| SECONDARY Activated Partial Thromboplastin Time (aPTT) Ratios to Baseline: Rivaroxaban Administered Three Times Daily (Suspension) in the Age Group Birth-<0.5 Years |
1.31; 1.21 | — |
| SECONDARY Anti-Xa Values: Rivaroxaban Administered Once Daily (Suspension and Tablet) in the Age Group 12-<18 Years |
164.46; 254.66; 255.40; 62.12 | — |
| SECONDARY Anti-Xa Values: Rivaroxaban Administered Once Daily (Suspension and Tablet) in the Age Group 6-<12 Years |
206.89; 263.24; 243.45; 27.39 | — |
| SECONDARY Anti-Xa Values: Rivaroxaban Administered Twice Daily (Suspension and Tablet) in the Age Group 6-<12 Years |
96.82; 139.10; 126.53; 47.49 | — |
| SECONDARY Anti-Xa Values: Rivaroxaban Administered Twice Daily (Suspension) in the Age Group 2-<6 Years |
177.78; 150.03; 54.40 | — |
| SECONDARY Anti-Xa Values: Rivaroxaban Administered Twice Daily (Suspension) in the Age Group 0.5-<2 Years |
247.54; 160.71; 121.09 | — |
| SECONDARY Anti-Xa Values: Rivaroxaban Administered Three Times Daily (Suspension) in the Age Group 2-<6 Years |
209.67; 140.46; 62.56 | — |
| SECONDARY Anti-Xa Values: Rivaroxaban Administered Three Times Daily (Suspension) in the Age Group 0.5-<2 Years |
111.35; 147.24; 23.40; 71.30 | — |
| SECONDARY Anti-Xa Values: Rivaroxaban Administered Three Times Daily (Suspension) in the Age Group Birth-<0.5 Years |
118.12; 228.03 | — |
Eligibility Criteria
Inclusion Criteria
- Children aged birth to 5x upper level of normal (ULN) or total bilirubin > 2x ULN with direct bilirubin > 20% of the total
- Platelet count 95th age percentile
- Life expectancy < 3 months
- Concomitant use of strong inhibitors of both cytochrome P450 isoenzyme 3A4 (CYP3A4) and P-glycoprotein (P-gp), including but not limited to all human immunodeficiency virus protease inhibitors and the following azole antimycotics agents: ketoconazole, itraconazole, voriconazole, posaconazole, if used systemically
- Concomitant use of strong inducers of CYP3A4, including but not limited to rifampicin, rifabutin, phenobarbital, phenytoin and carbamazepine
- Childbearing potential without proper contraceptive measures, pregnancy or breast feeding
Data sourced from ClinicalTrials.gov (NCT02234843) and the linked publication. 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. Informational only — not medical advice.