PCORI funds implementation projects that integrate evidence developed through PCORI-funded studies, in the context of the body of related evidence, into practice. This project focuses on implementing findings from this completed PCORI-funded research study: Comparing Two Medicines to Prevent Blood Clots after Treatment for Fractures -- The PREVENT CLOT Study.

1. What were the results from the original PCORI-funded research study?

The PREVENT CLOT trial enrolled 12,211 adult patients who sustained a surgically treated fracture in the legs, pelvis, or arms. The purpose of the trial was to compare two medications (aspirin and enoxaparin) to prevent blood clots. Based on patient feedback, the trial’s primary outcome was all-cause mortality, as these blood clots can be fatal. The study was a non-inferiority trial, meaning the risk of death in the aspirin group could be no worse than 0.75% higher than the risk of death with enoxaparin. The secondary outcomes for the trial included blood clots in the lungs (pulmonary embolism), blood clots in a deep vein (usually legs, deep vein thrombosis), and a bleeding complication during or after surgery. All outcomes were assessed 90 days after randomization.

Forty-seven of 6101 patients (0.8%) died in the aspirin group, and 45 of 6110 patients (0.7%) died in the enoxaparin group, suggesting the risk of a fatal event was not significantly higher with aspirin. Second, 90 patients (1.5%) in the aspirin group and 90 patients (1.5%) in the enoxaparin group developed blood clots in their lungs. Third, blood clots in a deep vein occurred in 151 patients (2.5%) in the aspirin group and 103 patients (1.7%) in the enoxaparin group, suggesting enoxaparin was better at preventing this complication. Finally, the 90-day bleeding complication rates were similar in both treatment groups (aspirin, 14% vs. enoxaparin, 14%).

The New England Journal of Medicine has accepted a PREVENT CLOT trial manuscript for publication.

2. Why is this research finding important?

Each year, over 1 million American sustain an operatively treated fracture. These injuries, the surgery, and immobilization after treatment increase the risk of a blood clot. Current clinical guidelines recommend enoxaparin to prevent blood clots after a fracture. However, research has demonstrated that patients have a strong preference for and improved adherence to orally administered medications like aspirin compared with medications administered by needle injection, like enoxaparin. In addition, enoxaparin can be extremely costly (list price of $1,076 - $1,435, depending on dosing, per course of treatment). One in five patients who sustain an orthopaedic injury in the United States is uninsured. Prescribing only enoxaparin to prevent blood clots in this patient population also widens the health equity gap as it is prohibitively expensive for many patients who pay out-of-pocket or have high-deductible insurance plans.

PREVENT CLOT is the first large clinical trial to compare blood clot prevention medications in patients after a fracture. The findings provide high-quality evidence to challenge existing clinical guidelines and suggest aspirin should be considered for preventing blood clots after a fracture.

3. What is the goal of this project?

The primary goal of this project is to increase the reach of the PREVENT CLOT trial evidence to the target audience and accelerate the pace at which that message is received. The secondary goal is to improve healthcare providers’ confidence that their blood clot prevention prescription is supported by high-quality evidence. Third, dissemination initiatives will be assessed to see if they shift in blood clot prevention prescribing practices for patients with operatively treated fractures using national data from over 800 trauma centers.

4. What is the project team doing?

A dissemination strategy has been developed using the Commonwealth Fund’s eight-step Blueprint of Effective Strategies in the Dissemination of Evidence-Based Practices Through a National Quality Campaign. The target audience for dissemination activities will be the healthcare providers who determine the blood clot prevention medications administered and prescribed to patients with a surgically treated fracture. This group includes orthopaedic surgeons, general surgeons, nurse practitioners, and physician assistants.

Goals will be achieved through three phases and with the support of key project partners. First, the research team will determine the preferred dissemination channels and content formats for the target audience (phase I). Second, the research team will tailor the communication messages based on these preferences with a goal of reaching over 10,000 healthcare professionals involved in prescribing blood clot prevention medication to patients after a fracture (phase II). Finally, phase III will evaluate the effectiveness of the dissemination activities using surveys and data from over 800 US trauma centers.

Given the non-inferior result of PREVENT CLOT, the research team does not expect the dissemination initiative to improve the clinical outcomes of orthopaedic trauma patients. However, if the activities are successful, the research team anticipates substantial improvement in the patient experience of the target patient population, given preferences for oral administration over needle injections.

5. How is the team evaluating this project?

The evidence success will be defined by the following outcomes. The first is the number of target audience individuals reached directly through dissemination channels, including podcast listeners, webcast participants, evidence report downloads, and social media views. Second, the research team will use survey data to assess the target audience’s awareness of dissemination initiatives, and the change in knowledge and attitudes measured as practice patterns and any improvement in blood clot medication prescribing confidence. Finally, the research team will use national trauma center data to evaluate changes in blood medications administered to this patient population on an annual basis.

6. How is the team involving patients and others in making sure the findings reach people who can use them?

The PREVENT CLOT trial benefited from an engaged patient and stakeholder committee representing patients, payers, clinicians, and patient advocacy groups. This group is committed to contributing to the dissemination of the trial results. Professional societies, specifically the Orthopaedic Trauma Association and Eastern Association for the Surgery of Trauma, will be critical to the newly proposed activities. In addition, the project will be supported by LBG Health Content Solutions as an Agency of Record with Wolters Kluwer Health, the publisher for all medical and nursing journals representing the professional societies of the target audience. This partnership will allow for multi-touch, cross-promotional dissemination activities.

7. How will this project help ensure future uptake and use of findings from patient-centered outcomes research?

The research team is one year away from completing another 10,000-patient PCORI-funded Pragmatic Clinical Study (PREPARE trial) with an identical target audience. The knowledge gained through this project will be immediately applied to another PCORI-funded trial and accelerated adoption of high-quality, patient-centered evidence.