Comparative Effectiveness of Pulmonary Embolism Prevention After Hip and Knee Replacement: Balancing Safety and Effectiveness
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 18,883
- 试验地点
- 52
- 主要终点
- Patient Well- Being
研究概览
简要总结
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.
详细描述
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
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Supportive Care
- 盲法
- None
入排标准
- 年龄范围
- 21 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
Arm 1: Enteric Coated Aspirin
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.
干预措施: Enteric Coated Aspirin (Drug)
Arm 2: Warfarin Other Names: Coumadin
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).
干预措施: Warfarin (Drug)
Arm 3: Rivaroxaban Other Names: Xarelto
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.
干预措施: Rivaroxaban (Drug)
结局指标
主要结局
Patient Well- Being
时间窗: Within 6 months of operation
To compare the groups with respect to patient-reported outcomes in order to assess their impact on general patient well-being. Validated functional outcome tools will be compared among patients with and without primary endpoint events, as well as with historical baseline data warehoused in the FORCE registry, a national AHRQ funded joint replacement outcomes database. Study site overlap with the FORCE registry is planned.
Specific Joint Function
时间窗: Within 6 months of operation
To compare the groups with respect to patient-reported outcomes in order to assess their impact on specific function of the replaced joint. Validated functional outcome tools will be compared among patients with and without primary endpoint events, as well as with historical baseline data warehoused in the FORCE registry, a national Agency for Healthcare Research and Quality (AHRQ) funded joint replacement outcomes database. Study site overlap with the FORCE registry is planned.
The frequency and nature of bleeding complications
时间窗: Within 6 months of operation
To compare the frequency and nature of bleeding complications (major, clinically important, and wound-related) leading to wound drainage, reoperation, deep infection, or myocardial infarction among three different VTE prophylaxis regimens.
Aggregate primary clinical endpoints of all-cause mortality plus PE and DVT
时间窗: Within 6 months of operation
To compare the frequency of the aggregate primary clinical endpoints of important venous thromboembolism (clinical PE and DVT confirmed by imaging and leading to hospital readmission and/or therapeutic anticoagulation) and all-cause mortality (aggregate indicator of fatal events, including both PE and major hemorrhage related to anticoagulant use) among three different venous thromboembolism (VTE) prophylaxis regimens. An audit of all hospital readmissions within 6 months of operation will be accomplished by routine postoperative follow-up through a mechanism of central telephone surveillance of patient-reported outcome events that is augmented by on-site research coordinator follow-up and validation of suspected endpoint events and adverse outcomes.
次要结局
- Comparative frequency of thromboembolic events and bleeding complications occurring after hip and knee replacement(Within 6 months of operation)
- "Standard of care" methods of anesthesia on clinical effectiveness of three different prophylaxis regimens based on adverse events(Within 6 months of operation)
研究者
Vincent D. Pellegrini
Professor of Orthopaedics
Dartmouth-Hitchcock Medical Center