Comparative Effectiveness of Pulmonary Embolism Prevention After Hip and Knee Replacement
Key facts
- Who runs it
- Dartmouth-Hitchcock Medical Center
- Where
- Alexandria, Baltimore, Boston, Burlington, Charleston, Charlottesville, Chicago, Cleveland, Durham, East Providence, Hershey, Indianapolis, Lebanon, Little Rock, Los Angeles, Morgantown, New York, Omaha, Philadelphia, Richmond, Rochester, Salt Lake City, Scottsdale, Seattle, South Miami, and Stanford, United StatesSee the 30 sitesAlso in 1 other country, 2 sites
- Trial code
- Status
- Completed
- Phase
- Phase 4
- People taking part
- 18,883 people enrolled
- Started
- Dec 2016
- Ended
- Sept 2025
- Type of study
- Interventional, 3 groups
- Treatments tested
- Enteric Coated Aspirin
- Warfarin
- Rivaroxaban
- Record updated
- 5 October 2026
Who can take part
- Age
- 21 years and older
- Sex
- Women and men
- Healthy volunteers
- Cannot take part
The registry criteria, word for word
Show all 18 criteriaShow less
Who can take part
- 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
Who cannot take part
- Has been previously enrolled
- 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 uncontrolled hypertension with systolic BP > 220mmHg or diastolic BP > 120mmHg
- Undergoing bilateral hip or knee replacement
- Is pregnant or breastfeeding
- Has had an operative procedure involving the eye, ear, or central nervous system within one month
- Body weight of less than 41 kilograms at baseline visit
- Member of a vulnerable patient population
Where in United States
Also in 1 other country, 2 sites
- Anderson Orthopaedic Institute (VA)Alexandria, United States
- Johns Hopkins UniversityBaltimore, United States
- Sinai HospitalBaltimore, United States
- Beth Israel Deaconess Medical CenterBoston, United States
- Boston University Medical CenterBoston, United States
- Brigham & Women's HospitalBoston, United States
- Lahey ClinicBurlington, United States
- Medical University of South CarolinaCharleston, United States
- University of VirginiaCharlottesville, United States
- Rush University Medical CenterChicago, United States
- Cleveland ClinicCleveland, United States
- Duke University Medical CenterDurham, United States
- Lifespan HealthEast Providence, United States
- Penn State Hershey Med CenterHershey, United States
- Indiana UniversityIndianapolis, United States
- Dartmouth Hitchcock Medical CenterLebanon, United States
- University of Arkansas for Medical SciencesLittle Rock, United States
- UCLALos Angeles, United States
- West Virginia UniversityMorgantown, United States
- New York UniversityNew York, United States
- Northwell HealthNew York, United States
- University of Nebraska Medical CenterOmaha, United States
- University of PennsylvaniaPhiladelphia, United States
- Virginia Commonwealth University Medical CenterRichmond, United States
- Mayo ClinicRochester, United States
- University of UtahSalt Lake City, United States
- Mayo ClinicScottsdale, United States
- University of WashingtonSeattle, United States
- Arthritis Surgery Research FoundationSouth Miami, United States
- Stanford University HospitalStanford, United States
About the trial
What the trial wants to find out
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.
The 3 groups in the trial
- Arm 1: Enteric Coated AspirinTreatment being tested
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.
Treatment: Enteric Coated Aspirin
- Arm 2: Warfarin Other Names: CoumadinTreatment being tested
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).
Treatment: Warfarin
- Arm 3: Rivaroxaban Other Names: XareltoTreatment being tested
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.
Treatment: Rivaroxaban
Results explained
A paper that names this trial, explained in plain words.
Data and sources
- Registry record
- Listed on ClinicalTrials.gov.
- Official title
- Comparative Effectiveness of Pulmonary Embolism Prevention After Hip and Knee Replacement: Balancing Safety and Effectiveness
- Publications
- Prevention of Venous Thromboembolism after Total Hip or Knee Replacement.The New England journal of medicine, 2026
- Record updated
- 5 October 2026