Comparative Effectiveness of Pulmonary Embolism Prevention After Hip and Knee Replacement (PEPPER)
Pulmonary Embolism, Venous Thrombosis
About this trial
This is an interventional supportive care trial for Pulmonary Embolism focused on measuring Anticoagulant, Venous Thromboembolism, Pulmonary Embolism, Total Knee Arthroplasty, Total Hip Arthroplasty
Eligibility Criteria
Inclusion Criteria:
- 21 years of age or older;
- Undergoing elective primary, revision or second stage re-implantation total hip/knee replacement or uni-compartmental knee replacement or hip resurfacing arthroplasty;
- Has necessary mental capacity to participate and is able to comply with study protocol requirements;
- Eligible for randomization to at least two of the three study regimens;
- Is not pregnant on the day of surgery;
- Has signed the consent form; and
- Is willing to be randomized and participate in the study.
Exclusion Criteria:
- Undergoing bilateral hip or knee replacement;
- Has been previously enrolled;
- Is pregnant or breastfeeding;
- Is on chronic anticoagulation other than antiplatelet medications;
- Concurrently enrolled in another active interventional clinical trial testing a drug or intervention known or believed to interact with aspirin, warfarin, or rivaroxaban;
- Has documented gastrointestinal, cerebral, or other hemorrhage within 3 months;
- Has a known diagnosis of defective hemostasis and past history of clinical bleeding requiring transfusion and treatment;
- Has had an operative procedure involving the eye, ear, or central nervous system within one month;
- Has uncontrolled hypertension with systolic BP > 220mmHg or diastolic BP > 120mmHg;
- Body weight of less than 41 kilograms at baseline visit;
- Member of a vulnerable patient population.
Sites / Locations
- Mayo ClinicRecruiting
- University of Arkansas for Medical Sciences
- UCLA
- Stanford University HospitalRecruiting
- Arthritis Surgery Research Foundation
- Rush University Medical Center
- Indiana University
- Sinai HospitalRecruiting
- Johns Hopkins UniversityRecruiting
- Brigham & Women's HospitalRecruiting
- Boston University Medical CenterRecruiting
- Beth Israel Deaconess Medical CenterRecruiting
- Lahey ClinicRecruiting
- Mayo ClinicRecruiting
- University of Nebraska Medical CenterRecruiting
- Dartmouth-Hitchcock Medical CenterRecruiting
- New York University
- Northwell HealthRecruiting
- Duke University Medical Center
- Cleveland ClinicRecruiting
- Penn State Hershey Med Center
- University of PennsylvaniaRecruiting
- Lifespan HealthRecruiting
- Medical University of South CarolinaRecruiting
- Anderson Orthopaedic Institute (VA)
- University of VirginiaRecruiting
- Virginia Commonwealth University Medical CenterRecruiting
- University of WashingtonRecruiting
- West Virginia UniversityRecruiting
- London Health Sciences CentreRecruiting
- University of OttawaRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Experimental
Experimental
Experimental
Arm 1: Enteric Coated Aspirin
Arm 2: Warfarin Other Names: Coumadin
Arm 3: Rivaroxaban Other Names: Xarelto
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.
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).
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.