Comparative Effectiveness of Pulmonary Embolism Prevention After Hip and Knee Replacement
Purpose
PEPPER is a randomized study comparing the three most commonly used anticoagulants in North America in patients who have elected to undergo primary or revision hip or knee joint replacement surgery. The anticoagulants being compared are enteric coated aspirin, low intensity warfarin, and rivaroxaban.
Conditions
- Pulmonary Embolism
- Venous Thrombosis
Eligibility
- Eligible Ages
- Over 21 Years
- Eligible Genders
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- 21 years of age or older; 2. Undergoing elective primary, revision or second stage re-implantation total hip/knee replacement or uni-compartmental knee replacement or hip resurfacing arthroplasty; 3. Has necessary mental capacity to participate and is able to comply with study protocol requirements; 4. Eligible for randomization to at least two of the three study regimens; 5. Is not pregnant on the day of surgery; 6. Has signed the consent form; and 7. Is willing to be randomized and participate in the study.
Exclusion Criteria
- Undergoing bilateral hip or knee replacement; 2. Has been previously enrolled; 3. Is pregnant or breastfeeding; 4. Is on chronic anticoagulation other than antiplatelet medications; 5. Concurrently enrolled in another active interventional clinical trial testing a drug or intervention known or believed to interact with aspirin, warfarin, or rivaroxaban; 6. Has documented gastrointestinal, cerebral, or other hemorrhage within 3 months; 7. Has a known diagnosis of defective hemostasis and past history of clinical bleeding requiring transfusion and treatment; 8. Has had an operative procedure involving the eye, ear, or central nervous system within one month; 9. Has uncontrolled hypertension with systolic BP > 220mmHg or diastolic BP > 120mmHg; 10. Body weight of less than 41 kilograms at baseline visit; 11. Member of a vulnerable patient population.
Study Design
- Phase
- Phase 4
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel Assignment
- Primary Purpose
- Supportive Care
- Masking
- None (Open Label)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental Arm 1: Enteric Coated Aspirin |
Enteric coated aspirin (162 mg po) will be administered on the day of operation, prior to surgery, with a sip of water. Thereafter, starting on postoperative day #1, all patients in the aspirin group will receive 81 mg po bid to complete the treatment period of 30 days. Patients on preoperative cardiac dose aspirin may continue their usual dosing regimen prior to the morning of surgery, and then commence the PEPPER trial aspirin dose of 81 mg po bid on the day after operation. |
|
|
Experimental Arm 2: Warfarin Other Names: Coumadin |
Warfarin will be administered starting on the day of operation, prior to surgery, with a sip of water. The initial dose will be empirically determined by body weight: less than 125 lbs (56.7 kg) - 2.5 mg; 125-250 lbs (56.7-113.4 kg) - 5 mg; greater than 250 lbs (113.4 kg) - 7.5mg. The initial dose will be repeated on the evening of surgery if the preoperative dose was administered prior to noon on the day of operation; no warfarin will be given on the evening of surgery if the preoperative dose was received after noon on the day of operation. Thereafter, starting on postoperative day #1, warfarin will be given each evening based on INR values to achieve a target of 2.0 (range 1.7-2.2). |
|
|
Experimental Arm 3: Rivaroxaban Other Names: Xarelto |
Rivaroxaban 10 mg will be first administered approximately 24 hours after completion of the index operation. Medication will then be administered in the evening on postoperative day #2 and thereafter each evening until completion. |
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Recruiting Locations
Boston, Massachusetts 02118
More Details
- Status
- Recruiting
- Sponsor
- Dartmouth-Hitchcock Medical Center
Detailed Description
PEPPER is a large pragmatic clinical trial to inform patient choice and balance risk tolerances of individuals who face decisions about different drugs and strategies for deep vein thrombosis (DVT) and pulmonary embolism (PE) prevention after total hip (THA) and knee (TKA) replacement. Indeed, clinical equipoise exists to ethically support such a randomized trial that has great potential to change current practice. We have selected the three prophylaxis methods that represent current orthopaedic practice in North America and collectively account for more than 80% of all hip and knee replacements; a) enteric coated aspirin (regimen with lowest bleeding risk; clinical PE and all-cause mortality rates comparable to more intensive anticoagulants), b) low intensity (INR Target 2.0) warfarin (time honored and one of the most common North American regimens; low bleeding risk [1-2%]), and c) rivaroxaban, a new oral direct Factor Xa inhibitor (regimen with lowest PE and DVT rate but higher bleeding risk [3-5%]). Prophylaxis will continue for 30 days, in accordance with clinical guidelines, and pneumatic compression will be utilized in hospital in conjunction with each treatment group. Each regimen is commonly used in contemporary practice, supported by observational and clinical trial data, and endorsed by the American College of Chest Physicians (ACCP) and American Academy of Orthopaedic Surgeons (AAOS) guidelines