Table 2.
Study design, efficacy endpoints, and safety outcomes in the phase III EINSTEIN studies of rivaroxaban for the prevention of VTE.
| Study | Design | Population | N | Regimen | Duration | Endpoints |
|---|---|---|---|---|---|---|
| EINSTEIN DVT | Open label | Patients with acute, symptomatic objectively confirmed proximal DVT without symptomatic PE | 3449 | Rivaroxaban 15 mg twice daily for 3 weeks, followed by 20 mg once daily | Rivaroxaban for 3, 6, or 12 months |
Efficacy endpoints
•Primary: symptomatic, recurrent VTE (the composite of DVT or fatal or nonfatal PE) |
| Enoxaparin 1 mg/kg body weight twice daily plus a VKA (warfarin or acenocoumarol), followed by dose-adjusted VKA only (target INR of 2.0–3.0) | Enoxaparin plus VKA continued until INR ≥2.0 for 2 consecutive days, and ≥5 days of enoxaparin therapy had been administered; followed by dose-adjusted VKA (target INR of 2.0–3.0) for the remainder of the treatment period (a total of 3, 6, or 12 months) |
Safety outcomes
•Primary: clinically relevant bleeding (the composite of major* or nonmajor† clinically relevant bleeding) |
||||
|
| ||||||
| EINSTEIN Extension | Double blind | Patients with objectively confirmed symptomatic DVT/PE, treated for 6–12 months with acenocoumarol, warfarin, or rivaroxaban, if there was equipoise with respect to the need for continued anticoagulation | 1197 | Rivaroxaban 20 mg once daily Placebo |
Rivaroxaban for 6 or 12 months Placebo for 6 or 12 months |
Efficacy endpoints
•Primary: symptomatic, recurrent VTE (the composite of DVT or nonfatal or fatal PE) Safety outcomes •Primary: major bleeding |
|
| ||||||
| EINSTEIN PE | Open label | Patients with acute, symptomatic, objectively confirmed PE with or without symptomatic DVT | 4832 | Rivaroxaban 15 mg twice daily for 3 weeks, followed by 20 mg once daily | Rivaroxaban for 3, 6, or 12 months |
Efficacy endpoints
•Primary: symptomatic, recurrent VTE (the composite of DVT or fatal or nonfatal PE) |
| Enoxaparin 1 mg/kg body weight twice daily plus a VKA (warfarin or acenocoumarol), followed by dose-adjusted VKA only (target INR of 2.0–3.0) | Enoxaparin plus VKA continued until INR ≥2.0 for 2 consecutive days, and ≥5 days of enoxaparin therapy had been administered; followed by dose-adjusted VKA (target INR of 2.0–3.0) for the remainder of the treatment period (a total of 3, 6, or 12 months) |
Safety outcomes
•Primary: clinically relevant bleeding (the composite of major* or nonmajor† clinically relevant bleeding) |
||||
Clinically overt and associated with a fall in hemoglobin level of ≥2 g/dl, if it led to transfusion of ≥2 units of red cells, or if it was retroperitoneal, intracranial, occurred in a critical site, or contributed to death.
Nonmajor clinically relevant bleeding was defined as overt bleeding not meeting the criteria for major bleeding but associated with medical intervention, unscheduled contact with a physician, interruption or discontinuation of study treatment, or associated with any other discomfort such as pain or impairment of activities of daily life.
DVT, deep vein thrombosis; INR, international normalized ratio; PE, pulmonary embolism; VKA, vitamin K antagonist; VTE, venous thromboembolism.