Rivaroxaban Superior To Enoxaparin For Prevention Of VTE In Patients Undergoing Knee Replacement Surgery, Phase III Trial Shows

July 9, 2007 – 11:11 pm | posted in Bones / Orthopaedics

Late-breaking Phase III clinical trial data presented today at the XXI International Society on Thrombosis and Haemostasis (ISTH) Congress demonstrate that once-daily rivaroxaban (Xarelto®) achieved superior efficacy in the prevention of venous thromboembolism (VTE) in patients undergoing knee replacement surgery in a head-to-head comparison with enoxaparin, the current standard of care therapy. Patients in the RECORD3 (REgulation of Coagulation in major Orthopaedic surgery reducing the Risk of DVT and PE) study who were treated with rivaroxaban demonstrated a 49% relative risk reduction (RRR) (p<0.001) of the composite primary endpoint of deep vein thrombosis (DVT), non-fatal pulmonary embolism (PE) and all-cause mortality compared to those treated with enoxaparin. An even greater (62%) reduction of risk (p=0.01) of developing major VTE (the composite of proximal DVT, non-fatal PE and VTE-related death), the secondary endpoint of the trial, was observed in the patients treated with rivaroxaban. Importantly, rivaroxaban also demonstrated a similarly low rate of major bleeding compared to enoxaparin (0.6% and 0.5%, respectively).

Rivaroxaban is an investigational, oral, once-daily direct Factor Xa inhibitor. It is an anticoagulant (a drug designed to prevent and treat blood clots) in advanced clinical development for the prevention and treatment of thrombosis in acute and chronic settings, enabling convenient administration in both the hospital and at home.

Rivaroxaban is being jointly developed by Bayer HealthCare AG and Johnson & Johnson Pharmaceutical Research & Development (J&JPRD), L.L.C.

Lead RECORD3 investigator, Michael R. Lassen, MD, of Hoersholm Hospital, University of Copenhagen, Denmark, commented: “The RECORD3 results are exciting, as they indicate that rivaroxaban may better meet the needs of many patients undergoing orthopaedic surgery. It’s an important step for this category that a once-daily, oral medication has demonstrated better efficacy in preventing VTE than the current standard of care, while also displaying a promising safety profile. In addition, it is important to note that symptomatic VTE, a secondary endpoint of the study, showed results in favour of rivaroxaban.”

Detailed Study Results

RECORD3 is a 2,531-patient, Phase III, double-blind trial that assessed the safety and efficacy of 10 mg oral, once-daily rivaroxaban started 6-8 hours after surgery versus 40 mg subcutaneous, once-daily enoxaparin started the evening before surgery in elective total knee replacement (TKR) surgery. Both regimens were continued for 10-14 days. The primary efficacy endpoint of the study was the composite of DVT, as diagnosed by mandatory venography, non-fatal PE and all-cause mortality. The primary safety endpoint was major bleeding. Results showed that DVT, non-fatal PE and death occurred in 9.6% (79/824) of patients receiving rivaroxaban versus 18.9% (166/878) of patients receiving enoxaparin (RRR 49%; p < 0.001).

Major VTE (the composite of proximal DVT, non-fatal PE and VTE-related death) - the main secondary efficacy endpoint of the study - occurred in 1.0% of the rivaroxaban-treated group and in 2.6% of the enoxaparin-treated group. The difference was statistically significant (p=0.01) in favour of rivaroxaban, with an RRR of 62%.

A reduction was also demonstrated in symptomatic VTE, a pre-specified additional secondary endpoint in the study. Symptomatic VTE occurred in 1.0% of patients who received rivaroxaban, compared to 2.7% of those in the enoxaparin comparator group, resulting in an RRR of 64%.

In the rivaroxaban and enoxaparin groups, major bleeding rates were 0.6% and 0.5%, and any bleeding rates were 4.9% and 4.8%, respectively. The RECORD3 trial demonstrated superior efficacy of rivaroxaban versus enoxaparin, with similarly low bleeding rates, in patients undergoing TKR.

Head of Global Development Dr. Kemal Malik, a member of Bayer HealthCare Executive Committee and management board member of Bayer Schering Pharma, commented: “Based on the data we have generated, rivaroxaban shows great promise that it could set a new standard of care in thromboembolic disease as a new benchmark for balancing safety and efficacy in anticoagulation. We hope that the clinical trials will continue to demonstrate the compelling efficacy and safety profile for rivaroxaban, while also demonstrating its utility in both the hospital and home settings without the need for routine monitoring.”

The trade name of rivaroxaban is expected to be Xarelto®, pending health authority approval.

Additional Phase III results of the ongoing RECORD program are expected to be available during H2 2007.

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