Clinical trial NCT02810704: Comparative Effectiveness of Pulmonary Embolism Prevention After Hip and Knee Replacement
Official title: Comparative Effectiveness of Pulmonary Embolism Prevention After Hip and Knee Replacement: Balancing Safety and Effectiveness
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE4
Conditions: Pulmonary Embolism
Venous Thrombosis
Keywords: Anticoagulant
Venous Thromboembolism
Pulmonary Embolism
Total Knee Arthroplasty
Total Hip Arthroplasty
Lead sponsor: Dartmouth-Hitchcock Medical Center
Sponsor class: OTHER
Collaborators: name: Patient-Centered Outcomes Research Institute
name: University of Maryland, Baltimore
name: Brigham and Women's Hospital
name: Northwestern University
name: Medical University of South Carolina
First posted: 2016-06-23
Enrollment: 20000
Sex: ALL
Minimum age (years): 21
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

Brief summary: 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.

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

Eligibility criteria: Inclusion Criteria:

1. 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:

1. 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.

Primary outcomes:
measure: Aggregate primary clinical endpoints of all-cause mortality plus PE and DVT
timeFrame: Within 6 months of operation
measure: The frequency and nature of bleeding complications
timeFrame: Within 6 months of operation
measure: Specific Joint Function
timeFrame: Within 6 months of operation
measure: Patient Well- Being
timeFrame: Within 6 months of operation
Secondary outcomes:
measure: "Standard of care" methods of anesthesia on clinical effectiveness of three different prophylaxis regimens based on adverse events
timeFrame: Within 6 months of operation
measure: Comparative frequency of thromboembolic events and bleeding complications occurring after hip and knee replacement
timeFrame: Within 6 months of operation
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Mayo Clinic
state: Arizona
city: Little Rock
country: United States
facility: University of Arkansas for Medical Sciences
state: Arkansas
city: Los Angeles
country: United States
facility: UCLA
state: California
city: Stanford
country: United States
facility: Stanford University Hospital
state: California
city: South Miami
country: United States
facility: Arthritis Surgery Research Foundation
state: Florida
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
city: Baltimore
country: United States
facility: Sinai Hospital
state: Maryland
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Boston
country: United States
facility: Brigham & Women's Hospital
state: Massachusetts
city: Boston
country: United States
facility: Boston University Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Burlington
country: United States
facility: Lahey Clinic
state: Massachusetts
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: Lebanon
country: United States
facility: Dartmouth-Hitchcock Medical Center
state: New Hampshire
city: New York
country: United States
facility: New York University
state: New York
city: New York
country: United States
facility: Northwell Health
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Hershey
country: United States
facility: Penn State Hershey Med Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: East Providence
country: United States
facility: Lifespan Health
state: Rhode Island
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Alexandria
country: United States
facility: Anderson Orthopaedic Institute (VA)
state: Virginia
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
city: Richmond
country: United States
facility: Virginia Commonwealth University Medical Center
state: Virginia
city: Seattle
country: United States
facility: University of Washington
state: Washington
city: Morgantown
country: United States
facility: West Virginia University
state: West Virginia
city: London
country: Canada
facility: London Health Sciences Centre
state: Ontario
city: Ottawa
country: Canada
facility: University of Ottawa
state: Ontario
Study officials:
affiliation: Dartmouth-Hitchcock Medical Center
name: Vincent D Pellegrini, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Dartmouth-Hitchcock Medical Center
name: Carol A Lambourne, PhD
role: STUDY_DIRECTOR
References:
citation: Pellegrini VD Jr, Eikelboom J, McCollister Evarts C, Franklin PD, Goldhaber SZ, Iorio R, Lambourne CA, Magaziner JS, Magder LS; Steering Committee of The PEPPER Trial. Selection Bias, Orthopaedic Style: Knowing What We Don't Know About Aspirin. J Bone Joint Surg Am. 2020 Apr 1;102(7):631-633. doi: 10.2106/JBJS.19.01135. No abstract available.
citation: Pellegrini VD Jr, Eikelboom JW, Evarts CM, Franklin PD, Garvin KL, Goldhaber SZ, Iorio R, Lambourne CA, Magaziner J, Magder L; Steering Committee of the PEPPER Trial and the PEPPER Trial Investigators, funded by PCORI. Randomised comparative effectiveness trial of Pulmonary Embolism Prevention after hiP and kneE Replacement (PEPPER): the PEPPER trial protocol. BMJ Open. 2022 Mar 8;12(3):e060000. doi: 10.1136/bmjopen-2021-060000.
citation: Ko H, Pelt CE, Martin BI; PEPPER Investigators; Pellegrini VD Jr. Patient-reported outcomes following cemented versus cementless primary total knee arthroplasty: a comparative analysis based on propensity score matching. BMC Musculoskelet Disord. 2022 Oct 27;23(1):934. doi: 10.1186/s12891-022-05899-1.
citation: Finch DJ, Martin BI, Franklin PD, Magder LS, Pellegrini VD Jr; PEPPER Investigators. Patient-Reported Outcomes Following Total Hip Arthroplasty: A Multicenter Comparison Based on Surgical Approaches. J Arthroplasty. 2020 Apr;35(4):1029-1035.e3. doi: 10.1016/j.arth.2019.10.017. Epub 2019 Oct 17.