Phase III clinical trial results demonstrate that rivaroxaban (Xarelto), a one tablet/once-daily, oral investigational anticoagulant, showed superior efficacy in preventing venous blood clots in patients following total knee replacement (TKR), whilst maintaining low major bleeding rates.
The Record4 study compared rivaroxaban with the US-approved treatment regimen for injectable enoxaparin, a current standard of care.
Data from Record4 were presented at the 9th Annual Meeting of the European Federation of National Associations of Orthopaedics & Traumatology (EFORT) in Nice, France. Rivaroxaban is being jointly developed by Bayer HealthCare AG and Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
The Record4 data show that rivaroxaban (10mg tablet once-daily) provided TKR surgery patients with a statistically significant reduction of total venous thromboembolism (VTE) event rates over twice-daily injectable enoxaparin (6.9 per cent and 10.1 per cent, respectively). This corresponds to a 31per cent relative risk reduction (RRR) over enoxaparin (30mg injection twice-daily). The rate of major bleeding in the rivaroxaban-treated patients was low and not statistically different to the rate of major bleeding in the enoxaparin-treated patients (0.7 per cent and 0.3 per cent, respectively).
While the Record1, 2 and 3 studies compared rivaroxaban against enoxaparin 40 mg injected once-daily to reduce blood clots after major orthopaedic surgery, Record4 is the first trial to evaluate rivaroxaban against enoxaparin 30 mg injected subcutaneously twice-daily, which is the US Food and Drug Administration (FDA)-approved treatment regimen for enoxaparin. Record4 provides additional head-to-head trial evidence demonstrating superior efficacy of rivaroxaban compared to enoxaparin together with a similar low rate of major bleeding, and establishes rivaroxaban as the first oral anticoagulant to show superiority over this regimen of enoxaparin.
"The superior efficacy and similar adverse event profile of rivaroxaban demonstrated in Record4 are in line with the outstanding results of the earlier RECORD studies," said Dr AGG Turpie, Professor of Medicine, McMaster University, Canada and Principal Investigator for the RECORD program. "The success of this trial strengthens my belief that direct Factor Xa inhibition with rivaroxaban has the potential to revolutionize the way we prevent the formation of dangerous blood clots".
Record4 is part of the Record programme (Regulation of Coagulation in major Orthopaedic surgery reducing the Risk of DVT and PE), which involved more than 12,500 total hip or knee replacement surgery patients. The full Record data set will be used to support the new drug application for rivaroxaban in the US which is planned for submission in mid 2008.
"We are very pleased that rivaroxaban has once again exceeded our expectations", said Frank Misselwitz, MD, Head of Cardiovascular Development, Bayer HealthCare AG. "Record4 is a testament to the outstanding, robust and consistent results we have seen across the full Record programme".
VTE is a serious life-threatening condition. It includes deep vein thrombosis (DVT) - a blood clot in a deep vein (usually in the leg) - and pulmonary embolism (PE) - a blood clot in the lungs. These clots often break apart and travel through the bloodstream, blocking blood flow to vital organs. During hip or knee replacement procedures, the large veins of the leg that carry blood back to the heart are damaged which significantly increases the VTE risk for patients undergoing such major orthopaedic surgery. In fact, venous blood clots occur in 40-60 per cent of patients undergoing major orthopaedic surgery and not receiving preventative care.
Rivaroxaban is being jointly developed by Bayer HealthCare and Johnson & Johnson Pharmaceutical Research & Development, L.L.C. The extensive clinical trial programme for rivaroxaban makes it the most studied oral, direct Factor Xa inhibitor in the world today.