Speaker
Robert O’Toole, MD
Chief of Orthopaedics, R Adams Cowley Shock Trauma Center
Head, Division of Orthopaedic Trauma
Department of Orthopaedics
Director, Clinical Research, Department of Orthopaedics
University of Maryland School of Medicine
Keywords
Pragmatic trials, orthopedic surgery, orthopedic trauma, Venous thromboembolism
Key Points
- Venous thromboembolism (VTE) is a potentially fatal complication after orthopedic trauma. Prophylaxis (chemical or mechanical) reduces risk deep vein thrombosis (DVT) by around 50%. The North American guideline is to give Low Molecular Weight Heparin (LMWH) in cases of orthopedic trauma for VTE prophylaxis.
- Aspirin is now the most commonly used VTE prophylaxis for Arthroplasty patients, in which Aspirin and LMWH are both safe and effective prophylaxis options.
- Aspirin as an oral pill is a less expensive and easier option for the orthopedic trauma population, which has a high proportion of uninsured patients. Researchers aimed to test the safety and effectiveness of Aspirin use as prophylaxis in orthopedic trauma cases.
- A pilot study, called the ADAPT trial, demonstrated feasibility, similar in-patient compliance and similar post-discharge adherence for the 2 options.
- Through the Patient-Centered Outcomes Research Institute (PCORI), the team conducted a Discrete Choice Experiment (DCE), which highlighted patient concern for risk of death compared to risk of complication. This inspired the research team to shift the primary outcome to death.
- Aspirin vs. Low Molecular Weight Heparin for Thromboprophylaxis: A Randomized Clinical Trial of Over 12,000 Orthopedic Trauma Patients (PREVENT CLOT) was conducted through METRC at 21 centers across the country.
- The primary hypothesis was that all-cause mortality is non-inferior with Aspirin compared to LMWH among orthopedic trauma patients. The study required an FDA exemption because Aspirin is not approved for this indication. The pragmatic randomized control trial was designed from a hospital policy perspective.
- Adult patients who fit the inclusion criteria were randomized at the patient level and stratified by treatment site. Patients and clinicians were non-blinded.
- The primary outcome was all-cause mortality. Secondary outcomes were pulmonary embolism-related death, non-fatal pulmonary embolism, and DVT. Secondary safety outcomes were bleeding events, wound complications, and surgical site infections.
- The study found that Aspirin is non-inferior to LMWH in preventing all-cause mortality after orthopedic trauma. There were similar results in the secondary outcomes, except LMWH showed lower risk of distal DVT. Therefore, it can be considered an acceptable option when clinicians, patients and hospital consider these data.
- Using the Win Ratio, which strategically considers the primary outcome as well as secondary outcomes like patient satisfaction, the researchers found that Aspirin was still acceptable even among higher-risk patients.
Discussion Themes
-Researchers decided to use a two-arm study with only Aspirin because of its low cost and its use in orthopedic arthroplasty.
-While people may be interested in specific subpopulations or outcomes, the confidence interval is not adjusted for multiple comparisons, so slicing the data could risk spurious findings.
-Clinician buy-in and understanding the social component of clinical work was essential to the pragmatic trial.
-The research team did not run into institutional barriers in the trial, likely because of the opportunity of Aspirin to be a much lower cost option if proven safe and effective.
Tags
#pctGR, @Collaboratory1