Multi-Center Trial of More Than 12,000 Orthopedic Trauma Patients Likely to Change Standard of Care
Patients hospitalized with fractures typically receive an injectable blood thinner, low-molecular-weight heparin, to prevent life-threatening blood clots. A new clinical trial, however, found that inexpensive over-the-counter aspirin is just as effective. The findings, published today in the New England Journal of Medicine, may lead surgeons to change their practice and administer aspirin to these patients.
The multi-center randomized clinical trial, which included more than 12,000 patients at 21 trauma centers in the U.S. and Canada, is the largest trial ever conducted on orthopedic trauma patients. This multidisciplinary collaboration between orthopedic surgeons and trauma surgeons points to the importance of evaluating techniques used to prevent post-surgical complications, like blood clots and infections, through high-quality, head-to-head comparison studies.
The trial was co-led by the Department of Orthopaedics at the University of Maryland School of Medicine (UMSOM) and the Major Extremity Trauma Research Consortium (METRC) based at the Johns Hopkins Bloomberg School of Public Health.
“Many patients with fractures will likely strongly prefer to take a daily aspirin over receiving injections after we found that both give them similar outcomes for prevention of the most serious outcomes from blood clots,” said the study’s principal investigator Robert V. O’Toole, MD, the Hansjörg Wyss Medical Foundation Endowed Professor in Orthopaedic Trauma at UMSOM and Chief of Orthopaedics at the R Adams Cowley Shock Trauma Center at the University of Maryland Medical Center (UMMC). “We expect our findings from this large-scale trial to have an important impact on clinical practice that may even alter the standard of care.”
Blood clots cause as many as 100,000 deaths in the U.S. each year, according to the U.S. Centers for Disease Control (CDC). Patients who experience fractures that require surgery are at increased risk of developing blood clots in the lungs and limbs. Large clots in the lungs even can be life-threatening. Current guidelines recommend prescribing low-molecular-weight heparin (enoxaparin) to prevent these clots, although smaller clinical trials in total joint replacement surgery suggested a potential benefit of aspirin as a less-expensive, widely available option.
The study enrolled 12,211 patients with leg or arm fractures that necessitated surgery or pelvic fractures regardless of the treatment. Half were randomly assigned to receive 30 mg. of injectable low molecular-weight heparin twice daily. The other half received 81 mg. of aspirin twice daily. Patients were followed for 90 days to measure health outcomes from the two treatments.
The main finding of the study was that aspirin was “non-inferior,” or no worse than low molecular-weight heparin in preventing death from any cause – 47 patients in the aspirin group died, compared with 45 patients in the heparin group. For other important complications, the researchers also found no differences between the two groups in clots in the lungs (pulmonary embolisms). The incidence of bleeding complications, infection, wound problems, and other adverse events from the treatments was also similar in both groups.
Of all the outcomes studied, the only potential difference noted was in blood clots in the legs, called deep vein thrombosis. This condition was relatively uncommon in both groups as it occurred in 2.5 percent of patients in the aspirin group, and in 1.7 percent of patients in the heparin group.
“This relatively small difference was driven by clots lower in the leg, which are thought to be of less clinical significance and often do not require treatment,” said study co-principal investigator Deborah Stein, MD, MPH, Professor of Surgery at UMSOM and Director of Adult Critical Care Services at UMMC.
The $11.7 million study was funded by the Patient-Centered Outcomes Research Institute (PCORI), (PCS-1511-32745), an independent, non-profit organization that funds comparative clinical effectiveness research to help patients and clinicians make better-informed healthcare decisions.
“This large multicenter study was needed to adequately measure the impact of prophylaxis on the infrequent, but important, outcome of death that is of utmost importance to patients,” said study methods center principal investigator Renan Castillo, PhD, Professor of Health Policy and Management at the Johns Hopkins Bloomberg School of Public Health.
The trial was called PREVENTion of CLots in Orthopaedic Trauma, or PREVENT CLOT. Patients enrolled in the trial were treated at the R Adams Cowley Shock Trauma Center at UMMC and 20 other trauma centers in 15 other states, as well as two in Canada. Recruitment started in April 2017 and continued through 2021.
“Many patients don’t like giving themselves injections. It’s not fun in terms of giving the actual injection because it burns, and your stomach tends to bruise more easily compared to aspirin,” said Debra Marvel, a 53-year-old from Columbia, MD, who served as a patient advisor on the study. She received Lovenox (low-molecular-weight heparin) after her legs were crushed in a 2015 pedestrian accident, requiring multiple surgeries at the University of Maryland Shock Trauma Center. “Patients also prefer aspirin because Lovenox can be expensive based on insurance.”
"An estimated one million Americans are hospitalized each year with extremity fractures, and this new finding could help prevent potentially fatal blood clots in these patients using a medication that is cheaper and far easier to administer,” said Mark T. Gladwin, MD, Vice President for Medical Affairs, University of Maryland, Baltimore, and the John Z. and Akiko K. Bowers Distinguished Professor and Dean, University of Maryland School of Medicine. "Given these important results, we can expect the guidelines for the prevention of blood clots to be revised to include the option of aspirin for patients with traumatic bone fractures."
Addressing the immense public health burden of orthopedic injuries, the Orthopedic Trauma Program at UMSOM ranks first in the U.S. for competitive research funding. Faculty treat some of the most complex patients in North America with a research focus aimed at reducing perioperative complications, improving fracture healing, and accelerating functional recovery after fracture surgery. A recent landmark clinical trial published by UMSOM Orthopedic Trauma faculty in The Lancet found that two antiseptic solutions routinely used by surgeons prior to fracture surgery are equally effective for preventing post-surgical infections.
About the R Adams Cowley Shock Trauma Center
The R Adams Cowley Shock Trauma Center, University of Maryland was the first fully integrated trauma center in the world and remains at the epicenter for trauma research, patient care, and teaching, both nationally and internationally today. Shock Trauma is where the "golden hour" concept of trauma was born and where many lifesaving practices in modern trauma medicine were pioneered. Shock Trauma is also at the heart of the Maryland's unparalleled Emergency Medical Service System. Learn more about Shock Trauma.
About the University of Maryland School of Medicine
Now in its third century, the University of Maryland School of Medicine was chartered in 1807 as the first public medical school in the United States. It continues today as one of the fastest growing, top-tier biomedical research enterprises in the world -- with 46 academic departments, centers, institutes, and programs, and a faculty of more than 3,000 physicians, scientists, and allied health professionals, including members of the National Academy of Medicine and the National Academy of Sciences, and a distinguished two-time winner of the Albert E. Lasker Award in Medical Research. With an operating budget of more than $1.3 billion, the School of Medicine works closely in partnership with the University of Maryland Medical Center and Medical System to provide research-intensive, academic, and clinically based care for nearly 2 million patients each year. The School of Medicine has nearly $600 million in extramural funding, with most of its academic departments highly ranked among all medical schools in the nation in research funding. As one of the seven professional schools that make up the University of Maryland, Baltimore campus, the School of Medicine has a total population of nearly 9,000 faculty and staff, including 2,500 students, trainees, residents, and fellows. The combined School of Medicine and Medical System (“University of Maryland Medicine”) has an annual budget of over $6 billion and an economic impact of nearly $20 billion on the state and local community. The School of Medicine, which ranks as the 8th highest among public medical schools in research productivity (according to the Association of American Medical Colleges profile) is an innovator in translational medicine, with 606 active patents and 52 start-up companies. In the latest U.S. News & World Report ranking of the Best Medical Schools, published in 2021, the UM School of Medicine is ranked #9 among the 92 public medical schools in the U.S., and in the top 15 percent (#27) of all 192 public and private U.S. medical schools. The School of Medicine works locally, nationally, and globally, with research and treatment facilities in 36 countries around the world. Visit medschool.umaryland.edu
About the University of Maryland Medical Center
The University of Maryland Medical Center (UMMC) is comprised of two hospital campuses in Baltimore: the 800-bed flagship institution of the 11-hospital University of Maryland Medical System (UMMS) and the 200-bed UMMC Midtown Campus. Both campuses are academic medical centers for training physicians and health professionals and for pursuing research and innovation to improve health. UMMC's downtown campus is a national and regional referral center for trauma, cancer care, neurosciences, advanced cardiovascular care, and women's and children's health, and has one of the largest solid organ transplant programs in the country. All physicians on staff at the downtown campus are clinical faculty physicians of the University of Maryland School of Medicine. The UMMC Midtown Campus medical staff is predominately faculty physicians specializing in a wide spectrum of medical and surgical subspecialties, primary care for adults and children and behavioral health. UMMC Midtown has been a teaching hospital for 140 years and is located one mile away from the downtown campus. For more information, visit www.umm.edu.