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The PEPPER Trial

The Pulmonary Embolism Prevention After HiP and KneE Replacement trial (PEPPER) is trying to determine which blood thinner works best after a hip or knee replacement. 



Nearly one million total hip and knee replacements are performed each year in the United States. Because disturbing the bone marrow cavity turns on the blood clotting system in humans, these operations can be complicated by formation of blood clots in the veins of the leg (deep vein thrombosis). These clots sometimes detach from the leg veins and travel to the lungs (pulmonary embolism, PE) where they interfere with the normal pumping of the blood from the heart. When a large clot gets stuck in the lung, it can result in death. The use of blood thinners around the time of operation reduces the risk of PE, but increases the risk of bleeding from the raw bony surfaces that are created when the joint replacement is done. The ideal balance between use of blood thinners to prevent PE and the risk of bleeding associated with their use is unknown.

The purpose of the study “Comparative Effectiveness of Pulmonary Embolism Prevention after Hip and Knee Replacement (PEPPER)” which is funded through a Patient-Centered Outcomes Research Institute (PCORI) award, is to combine information about effectiveness in preventing blood clots in the lungs and legs with the opinions of patients about the safety of the most commonly employed blood thinners. This work will provide background information to help both patients and their surgeons in deciding which blood thinner would be best to use after hip and knee replacement.

In order to generate enough data to achieve the purpose of PEPPER, approximately 25,000 patients undergoing elective total hip or knee replacements will be enrolled at 25 centers in the United States and Canada. The Principal Investigator for the PEPPER trial is Vincent Pellegrini, MD, the Vice Chair of Research and Education Affairs at Dartmouth-Hitchcock Medical Center.


The PEPPER study is supported by funding from the Patient Centered Outcomes Research Institute (PCORI). Click here to learn more about the PEPPER study on the PCORI website. Additional information can be found on

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