Table 4.
Rivaroxaban and dabigatran etexilate trial comparison.
| Einstein Jr phase 3, | DIVERSITY phase 3, | |||
|---|---|---|---|---|
| N = 500 | N = 267 | |||
| ( 15 ) | ( 25 ) | |||
| DOAC | Rivaroxaban | Dabigatran etexilate | ||
| Institutions and Countries | 107 institutions in 28 countries | 65 institutions in 26 countries | ||
| Enrollment period | 2014, Nov to 2018, Sept | 2014, Feb to 2019, Nov | ||
| Prior parenteral therapy duration | 5–9 days of UFH, LMWH or fondaparinux | 5–21 days of UFH or LMWH | ||
| Study treatment period | 3 months (1 month for <2 years of age with catheter related thrombosis) | 3 months | ||
| Patients enrolled | 500 | 267 | ||
| Randomization (intervention:SOC) | 2:1 | 2:1 | ||
| Trial type | Open label | Open label | ||
| Patients, N | ||||
| Intervention | SOC | Intervention | SOC | |
| Patients randomized, included in efficacy analysis | 335 | 165 | 177 | 90 |
| Parenteral therapy duration mean prior to randomization, days | Not defined | 15.7 | 14.8 | |
| Anticoagulation received | Rivaroxaban | UFH, LMWH, fondaparinux, or VKA | Dabigatran | UFH, LMWH, fondaparinux or VKA |
| VTE site (%) | ||||
| Cerebral venous or sinus thrombosis | 74 (22%) | 43 (26%) | 20 (11%) | 6 (7%) |
| Catheter related | 90 (27%) | 37 (22%) | 27 (15%) | 20 (22%) |
| Non-catheter related | 171 (51%) | 85 (52%) | 110 (62%) | 60 (67%) |
| Pulmonary embolism | Not defined | 20 (11%) | 4 (4%) | |
| Age distribution, years (%) | ||||
| 0 to <2 | 37 (11%) | 17 (10%) | 22 (12%) | 13 (14%) |
| 2 to <12 | 114 (34%) | 56 (34%) | 43 (24%) | 21 (23%) |
| 12 to <18 | 184 (55%) | 92 (56%) | 112 (63%) | 56 (62%) |
| Median exposure, days | 91 days (3-month treatment) and 31 days (1-month treatment) | 84.5 days | 85 days | |
| Patients included in safety analysis@ | 329 | 162 | 176 | 90 |
| Adverse events (%) | ||||
| Bleeding, major* | 0 (0%) | 2 (1%) | 4 (2%) | 2 (2%) |
| Bleeding, CRNM | 10 (3%) | 1 (<1%) | 2 (1%) | 1 (1%) |
| Treatment related deaths | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) |
| Thrombus endpoint# (%) | ||||
| Thrombus resolution, complete | 128 (38%) | 43 (26%) | 81 (46%) | 38 (42%) |
| Thrombus, recurrence | 4 (1%) | 5 (3%) | 7 (4%) | 7 (8%) |
Einstein Jr intervention, 6 patients did not initiate study medication and 7 patients did not continue in the trial after initiation; Einstein Jr SOC, 3 patients did not initiate study medication and 6 patients did not continue in the trial after initiation; Diversity intervention, 1 patient did not initiate study medication and 8 patients did not continue in the trial after initiation; Diversity SOC, 5 patients did not continue in the trial after initiation.
Major bleeding defined by Halton et al. (25) as fatal bleeding or ≥2 g/dL drop in hemoglobin in 24 h.
Remainder of thrombi were undefined.
CRNM, clinically relevant non-major; LMWH, low molecular weight heparin; SOC, standard of care; UFH, unfractionated heparin; VKA, vitamin K antagonist.