Close

move up move left move right move bottom

EINSTEIN Clinical Trial Program

The largest DVT and PE phase 3 clinical trial program ever conducted

The EINSTEIN clinical trial program consisted of three phase 3 clinical trials in more than 12,800 patients:

A pooled analysis of the EINSTEIN–DVT and –PE trials was conducted, including key prespecified subgroups, such as fragile* patients, those with cancer, and those with previous VTE.2

EINSTEIN CHOICE: Trial1

  • Comparison of the efficacy and safety of once-daily rivaroxaban 20 mg and 10 mg with aspirin (100 mg) in VTE patients who completed 6 to 12 months of treatment and were in equipoise regarding the need for extended anticoagulation

  • Randomized, double-blind, active-comparator, event-driven, superiority study

  • Primary efficacy outcome: A composite of symptomatic, recurrent fatal or nonfatal VTE and unexplained death for which PE could not be ruled out

  • Principal safety outcome: Major bleeding (defined according to the ISTH criteria)

  • Because the benefit-risk assessment favored the 10-mg dose versus aspirin compared to the 20-mg dose versus aspirin, the 10-mg dose is approved for the reduction in the risk of recurrent DVT/PE

  • View the study

    Equipoise = a state of uncertainty as to the balance of benefits and harm; ISTH = International Society on Thrombosis and Haemostasis.

EINSTEIN–DVT trial: Treating DVT

Chart showing the Einstein DVT Study design population that was objectively confirmed symptomatic proximal DVT without symptomatic PE taking XARELTO vs warfarin. Chart showing the Einstein DVT Study design population that was objectively confirmed symptomatic proximal DVT without symptomatic PE taking XARELTO vs warfarin.

The purpose of EINSTEIN–DVT was to compare the efficacy and safety of XARELTO® with standard therapy in 3449 patients with confirmed DVT (without symptomatic PE).3 XARELTO® was shown to be at least as effective as the standard of care (enoxaparin + warfarin). The safety data, pooled with the EINSTEIN–PE trial, showed comparable rates of the composite of major bleeding and clinically relevant nonmajor bleeding across treatment groups and lower rates of major bleeding for XARELTO®.2 View the study

  • Patients randomized to receive either XARELTO® or standard of care (enoxaparin + warfarin followed by warfarin) for 3, 6, or 12 months at physicians' discretion3

  • Primary efficacy outcome: symptomatic recurrent venous thromboembolism3

  • Principal safety outcome: composite of major bleeding and clinically relevant nonmajor bleeding3

EINSTEIN–PE trial: Treating PE

Chart showing population in XARELTO PE clinical trial objectively confirmed symptomatic proximal DVT with or without symptomatic PE who took Xarelto 15 mg twice daily and 20 mg once daily after 21st day vs warfarin Chart showing population in XARELTO PE clinical trial objectively confirmed symptomatic proximal DVT with or without symptomatic PE who took Xarelto 15 mg twice daily and 20 mg once daily after 21st day vs warfarin

The purpose of EINSTEIN–PE was to compare the efficacy and safety of XARELTO® with standard therapy in 4832 patients with confirmed PE (with or without symptomatic DVT).4 XARELTO® was proven at least as effective as the standard of care (enoxaparin + warfarin). The safety data, pooled with the EINSTEIN–DVT trial, showed comparable rates of the composite of major bleeding and clinically relevant nonmajor bleeding across treatment groups and lower rates of major bleeding for XARELTO®.2 View the study

  • Patients randomized to receive either XARELTO® or standard of care (enoxaparin + warfarin followed by warfarin) for 3, 6, or 12 months at physicians' discretion4

  • Primary efficacy outcome: symptomatic recurrent venous thromboembolism4

  • Principal safety outcome: composite of major bleeding and clinically relevant nonmajor bleeding4

Pooled subgroup analysis of the EINSTEIN–DVT and –PE trials

The purpose of the pooled analysis was to evaluate the combined efficacy and safety data of both trials. XARELTO® showed consistent outcomes versus standard of care (enoxaparin + warfarin) across prespecified subgroups.2 View the results

  • Both studies used identical designs, treatment regimens, outcome definitions, and adjudication processes to facilitate pooled analyses2

  • Key prespecified subgroups in the pooled analysis included fragile* patients, those with cancer, and those with previous VTE2

*Fragility was defined as one or more of these criteria: age >75 years, CrCl <50 mL/min, or body weight ≤50 kg.2

CrCl = creatinine clearance.

 

Indications

 

IMPORTANT SAFETY INFORMATION

 

Indication and Important saftey Information

 

  • Reducing the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation (AF). There are limited data on the relative effectiveness of XARELTO® (rivaroxaban) and warfarin in reducing the risk of stroke and systemic embolism when warfarin therapy is well controlled.
  • Treatment of deep vein thrombosis (DVT).
  • Treatment of pulmonary embolism (PE).
  • Reduction in the risk of recurrence of DVT and/or PE in patients at continued risk for recurrent DVT and/or PE after completion of initial treatment lasting at least 6 months.
  • Prophylaxis of DVT, which may lead to PE in patients undergoing knee replacement surgery.
  • Prophylaxis of DVT, which may lead to PE in patients undergoing hip replacement surgery.

References:

  1. Weitz JI, Lensing AWA, Prins MH, et al. Rivaroxaban or aspirin for extended treatment of venous thromboembolism. N Eng J Med. 2017; 376:1211-1222.
  2. Prins MH, Lensing AWA, Bauersachs R, et al, on behalf of the EINSTEIN Investigators. Oral rivaroxaban versus standard therapy for the treatment of symptomatic venous thromboembolism: a pooled analysis of the EINSTEIN-DVT and PE randomized studies. Thromb J. 2013;11(1):21.
  3. The EINSTEIN Investigators. Oral rivaroxaban for symptomatic venous thromboembolism. N Engl J Med. 2010;363(26):2499-2510.
  4. The EINSTEIN–PE Investigators. Oral rivaroxaban for the treatment of symptomatic pulmonary embolism. N Engl J Med. 2012;366(14):1287-1297.