Comparative Effectiveness of Pulmonary Embolism Prevention After Hip and Knee Replacement


About this study

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.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria:

  1. Males and females 21 years of age or older;
  2. Undergoing elective primary or revision hip or knee replacement;
  3. Patient has necessary mental capacity to participate and is able to comply with study protocol requirements;
  4. Patient is not pregnant;
  5. Patient has signed consent form; and
  6. Patient is wiling to be randomized and participate.

Exclusion Criteria:

  1. Patient is undergoing bilateral hips or knee replacement;
  2. No patient undergoing total hip or knee replacement who has been enrolled in this study for a prior hip or knee replacement;
  3. Women who are pregnant or breastfeeding;
  4. Patient is on chronic anticoagulation other than with antiplatelet medications;
  5. Patient is concurrently enrolled in another active interventional clinical trial testing a drug or intervention known or believed to interact with aspirin, warfarin, or rivaroxaban;
  6. Patient has a contraindication to two or more of the three prophylaxis regimens;
  7. Documented gastrointestinal, cerebral, or other hemorrhage within 3 months of the operation;
  8. A known diagnosis of defective hemostasis and past history of clinical bleeding requiring transfusion and treatment;

7) A known condition of thrombophilia proven by diagnostic laboratory testing; 9) An operative procedure involving the eye, ear, or central nervous system within one month; 10) Severe uncontrolled hypertension with systolic BP > 220mmHg or diastolic BP > 120mmHg; 11) An absolute body weight of less than 41 kilograms (90.4 lbs) at baseline; and 12) Vulnerable patient populations including prisoners, institutionalized individuals, and those who are mentally handicapped.

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Scottsdale/Phoenix, Ariz.

Mayo Clinic principal investigator

Mark Spangehl, M.D.

Open for enrollment

Contact information:

Vy Nguyen CCRP

(480) 342-1328

More information


  • More than 1 million elective total hip and knee replacements are performed annually in the USA with 2% risk of clinical pulmonary embolism (PE), 0.1%-0.5% fatal PE, and over 1000 deaths. Antithrombotic prophylaxis is standard of care but evidence is limited and conflicting. We will compare effectiveness of three commonly used chemoprophylaxis agents to prevent all-cause mortality (ACM) and clinical venous thromboembolism (VTE) while avoiding bleeding complications. Read More on PubMed

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