Randomized Trial of Aspirin Versus Rivaroxaban After Replacement of the Aortic Valve With a Biological Valve Prosthesis
Trial Snapshot
- Phase
- Phase 4
- Sponsor
- Enrollment
- 1,000
- Locations
- 4
- Primary Endpoint
- Combined: Death, Stroke, Myocardial infarction
Study Overview
Brief Summary
Aortic valve replacement with a biological prosthesis is the most common valve surgery performed with about 1000 operations performed in Denmark each year. Further, the introduction of percutaneous stent valves will increase these types of replacements in the years to come. A biological valve is a foreign body prone to cause thrombus formation at least until the valve is covered with recipient endothelium. There are no conclusive studies of anticoagulation and the investigators have shown stroke to be a common complication. Guidelines have variably recommended aspirin or rivaroxaban for anticoagulation, and currently aspirin is the most common recommendation. In a register study, the investigators have shown that proper anticoagulation with warfarin is likely to be superior. There is a clear need for a large randomised study of aspirin versus anticoagulation for biological aortic valve replacement. This protocol describes a randomised study where 1000 patients will be randomised to receive either rivaroxaban or aspirin for 6 months following aortic valve replacement with a biological prosthesis. The primary efficacy endpoint is a combined event of all-cause mortality and hospitalisation for either acute myocardial infarction or stroke. This study has the power to settle a discussion of appropriate anticoagulation for this operation
Detailed Description
Background
The study is a comparison of aspirin and rivaroxaban for the postoperative treatment after biological aortic valve replacement.
Scientific Background Guidelines have over the years recommended anticoagulation or aspirin after surgical replacement of the aortic valve with a prosthesis. There are no proper randomized trials. Rivaroxaban is an anticoagulant approved for several indications. The investigators are conducting a study to compare Aspirin versus Rivaroxaban for prevention of thrombosis during 6 months after aortic valve replacement with a biological prosthesis.
As a substudy CT scans for a subgroup of patients to detect partially immobilized valves due to thrombosis is performed.
Trial drugs The trial drugs are 100 mg Aspirin daily or 10 mg Rivaroxaban daily. Patients are provided with either 180 tablets of 10 mg rivaroxaban or 180 tablets of 100 mg aspirin.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Prevention
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 100 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Patients ≥ 18 years scheduled for surgical bioprosthetic aortic valve replacement.
- •Ability to understand the study background, risk and benefit of treatment and to give written informed consent
- •Scheduled for routine antithrombotic treatment after surgical valve replacement. Patient required to receive aspirin due to simultaneous by-pass operation are allowed in the study - to receive either aspirin alone or rivaroxaban in addition to aspirin.
Exclusion Criteria
- •Ongoing treatment with oral anticoagulants (warfarin, phenprocoumon or thrombin/factorXa oral anticoagulants).
- •Indication for oral anticoagulation treatment even if currently not treated (e.g. chronic atrial fibrillation, recent deep vein thrombosis, recent pulmonary embolism)
- •Indication for dual antiplatelet therapy (e.g. aspirin and ADP receptor inhibitor)
- •Known intolerance to aspirin or rivaroxaban.
- •Stroke within 6 months of study start.
- •Concomitant therapy with systemic drugs that are strong inhibitors of both CYP 3A4 and P-gp (azole antimycotics such as ketoconazole and itraconazole or HIV protease inhibitors such as ritonavir)
- •Concomitant therapy with drugs that are strong CYP 3A4 inducers (e.g. carbamazepine, phenytoin, rifampin, St. John's wort)
- •Platelet count of less than 90,000 per cubic millimeter
- •Preoperative anemia with hemoglobin <6mmol/l
- •Creatinine clearance (Cockroft formula) <15 ml/min
- •Clinically significant gastrointestinal bleeding within 3 months
- •Previous intracranial hemorrhage;
- •The presence of a severe or active bleeding disorder.
- •Non-adherence to medications
- •Pregnancy or risk of pregnancy. In women of childbearing age, an approved birth control must be ensured.
Arms & Interventions
Aspirin 100 mg
100 mg of aspirin daily for 180 days
Intervention: Aspirin (Drug)
Rivaroxaban 10 mg
10 mg of Rivaroxaban daily for 180 days
Intervention: Rivaroxaban 10 MG (Drug)
Outcomes
Primary Outcomes
Combined: Death, Stroke, Myocardial infarction
Time Frame: 6 months
The primary outcome is a combination of all-cause mortality, hospital admission for stroke and hospital admission for myocardial infarction. The main outcomes of the study are examined after 6 months.
Secondary Outcomes
- Bleeding(6 months)
- Fatal or non fatal thrombotic event(6 months)
- Cardiovascular Mortality(6 months)
- Reduced leaflet motion(3 months)
Investigators
Christian Torp-Pedersen
Professor
Aalborg University Hospital