Date: 2018-08-27
Type of
information: Presentation of results at a congress
phase: 3
Announcement: presentation of results aat ESC Congress 2018
Company: Bayer HealthCare (Germany) Janssen Research & Development (J&J) (USA - NJ)
Product: Xarelto® (rivaroxaban)
Action
mechanism: anticoagulant agent/oral direct Factor Xa inhibitor
Disease: patients with chronic heart failure (HF) and significant coronary artery disease (CAD)
Therapeutic
area: Cardiovascular diseases
Country: Argentina, Australia, Brazil, Bulgaria, Canada, China, Chzechia, Denmark, Estonia, France, Germany, Greece, Hungary, Japan, Replublic of Korea, Latvia, Lithuania, Malaysia, Mexico, The Netherlands, Poland, Portugal, Romania, Russian Federation, Slovakia, South Africa, Spain, Sweden, Turkey, Ukrain, UK, USA
Trial
details:
- COMMANDER HF is a Phase III international prospective, randomized, double-blind, placebo controlled, event-driven, parallel-group comparison, designed to evaluate the use of rivaroxaban in reducing the risk of morbidity and mortality in patients following an acute decompensation of heart failure and concomitant coronary artery disease. The study evaluated 5,025 patients from 32 countries worldwide following an acute decompensation of heart failure and significant coronary artery disease (CAD) who were already receiving appropriate treatment for their heart failure and CAD.
- Patients were randomized in a 1:1 ratio to receive either rivaroxaban 2.5 mg twice daily or placebo, both in combination with standard of care for heart failure and CAD (as prescribed by the patient’s physician). (NCT01877915)
-
MARINER is a Phase III randomized, double-blind, placebo-controlled trial, designed to evaluate the efficacy and safety of venous thromboembolism (VTE) prophylaxis in high-risk acutely medically ill patients using rivaroxaban, begun at hospital discharge and continued for 45 days. The study evaluated 12,024 patients aged ? 40 years from 36 countries worldwide who were hospitalized for 3-10 days prior to randomization for heart failure, acute respiratory insufficiency or acute exacerbation of chronic obstructive pulmonary disease (COPD), acute ischemic stroke, acute infectious diseases, or inflammatory diseases including rheumatic disease and were at an increased risk for VTE.Patients were randomized in a 1:1 ratio to receive either rivaroxaban 10 mg once daily (CrCl ? 50ml/min) or placebo for 45 days post hospital discharge; patients randomized to rivaroxaban with CrCl 30-<50ml/min received rivaroxaban 7.5 mg once daily. (NCT02111564)
Latest
news:
- • On August 27, 2018, Bayer and its development partner Janssen Research & Development announced new data from two investigational studies for its Factor Xa inhibitor rivaroxaban (Xarelto®) at ESC Congress 2018, 25-29 August in Munich, Germany. Data from the COMMANDER HF study showed that, in patients following an acute decompensation of heart failure and concomitant coronary artery disease, there was no statistically significant difference between rivaroxaban 2.5 mg twice daily and placebo, each on top of standard of care, in reducing the composite risk of all-cause mortality, heart attack and stroke. However, there were numerically fewer events for both heart attack and stroke in patients receiving rivaroxaban. Furthermore patients receiving rivaroxaban had similar and in general low rates of severe bleeding compared to those receiving placebo.
- For the primary efficacy outcome of the composite of all-cause mortality (ACM), heart attack and stroke, patients treated with rivaroxaban had an event rate of 13.44 (per 100 patients per year), compared to 14.27 in patients treated with placebo, with no statistical difference between the patient populations (hazard ratio (HR) 0.94; 95% confidence interval (CI) 0.84-1.05). Specifically, there were numerical reductions in the individual outcomes of heart attack and stroke in patients treated with rivaroxaban compared to placebo – relative risk reduction 17% (HR 0.83; 95% CI 0.63-1.08) and 34% (HR 0.66; 95% CI 0.47-0.95) respectively – however these were not statistically significant.
For the primary safety outcome of fatal bleeding or bleeding into a critical space with potential for permanent disability, rates for rivaroxaban were comparable to placebo (HR 0.80; 95% CI 0.43-1.49).
- Separately, data from the MARINER study showed that, compared to placebo, rivaroxaban 10 mg once daily (1) did not significantly reduce the composite of symptomatic venous thromboembolism (VTE) and VTE-related death post hospital discharge in high-risk acutely medically ill patients. The major bleeding rate with rivaroxaban was generally low, and not significantly different compared to placebo.
- The primary efficacy outcome of symptomatic VTE and VTE-related death occurred at a rate of 0.83% in patients treated with rivaroxaban compared to 1.10% in patients receiving placebo, a 24% relative risk reduction (HR 0.76, 95% CI 0.52-1.09). However this result was not statistically significant.
- There was a nominally significant 56% reduction in symptomatic VTE in patients treated with rivaroxaban compared to those treated with placebo, with an absolute difference of 0.24% (HR 0.44; 95% CI 0.22-0.89). VTE related death rates were lower in rivaroxaban group but not significantly different compared to placebo. Rates of major bleeding, the primary safety outcome, were generally low across both treatment groups, and not significantly different (0.28% vs 0.15%, HR 1.88, 95% CI 0.84-4.23).
- The positive benefit risk profile of rivaroxaban in the approved indications remains unchanged.
- • On March 8, 2013, Bayer HealthCare and its cooperation partner Janssen Research & Development have announced the initiation of COMMANDER-HF, a pivotal Phase III clinical trial that will evaluate Xarelto® (rivaroxaban) 2.5 mg twice daily in patients with chronic heart failure (HF) and significant coronary artery disease (CAD). Rivaroxaban is the first novel oral anticoagulant to be evaluated in this patient group who remain at high-risk for complications following hospitalization for exacerbation of their HF.
- "COMMANDER-HF will assess whether the addition of low-dose rivaroxaban on top of standard therapy can help reduce the risk of death, heart attack or stroke in this high-risk patient group following hospitalization,\" said Dr. Kemal Malik, Member of the Bayer HealthCare Executive Committee and Head of Global Development.
The FDA granted a fast track designation process for the COMMANDER-HF study to help facilitate the development process, and expedite the review of rivaroxaban in this indication.
- To date, Xarelto® is approved for six distinct uses in the venous arterial thromboembolic (VAT) space.
- • The prevention of stroke and systemic embolism in adult patients with non-valvular atrial fibrillation (AF) with one or more risk factors
- • The treatment of deep vein thrombosis (DVT) in adults
- • The treatment of pulmonary embolism (PE) in adults
- • The prevention of recurrent DVT and PE in adults
- • The prevention of venous thromboembolism (VTE) in adult patients undergoing elective hip replacement surgery
- • The prevention of venous thromboembolism (VTE) in adult patients undergoing elective knee replacement surgery.
Is
general: Yes
