Virtual, Cloud-Based PREVENT-HD Trial Evaluates Rivaroxaban to Prevent Thrombosis in COVID-19 Patients

May 16, 2023—The Feinstein Institutes for Medical Research at Northwell Health, which is based in Manhasset, New York, recently announced findings from the entirely virtual, outpatient, cloud-based PREVENT-HD trial, which the Feinstein Institutes helped to design and implement to understand the efficacy of rivaroxaban.

The multicenter, randomized clinical trial investigated rivaroxaban for prevention of thrombotic events, hospitalization, and death in outpatients with COVID-19. Rivaroxaban is a common prophylactic medication used to treat patients with venous and arterial thrombosis, including those with COVID-19 who are at higher risk.

The PREVENT-HD trial found no significant impact of rivaroxaban to prevent clots. The study findings along with its novel remote trial design were published by Gregory Piazza, MD, et al in Circulation.

Alex C. Spyropoulos, MD, who is a professor at the Feinstein Institutes’ Institute of Health System Science and Director of Anticoagulation and Clinical Thrombosis Services at Northwell Health, served as study Coprincipal Investigator.

“Since the start of the pandemic, we have been studying COVID-19, its risk to increase blood clots, and the best course of treatment, both in and out of the hospital,” commented Dr. Spyropoulos in the Feinstein Institutes press release. “The PREVENT-HD trial is a good model for how future outpatient clinical trials can be designed, harnessing patient data and embracing technology.”

As summarized in the Feinstein Institutes press release, more than 1,280 diverse, COVID-19-positive, symptomatic patients were virtually consented and enrolled in the trial from August 2020 to April 2022. The patients were identified through electronic health records and other clinical decision support tools, which helped detect patients at risk of a venous or arterial thrombosis event.

Rivaroxaban was prescribed daily for 35 days. The results show that it did not reduce the frequency of a composite outcome of symptomatic major thromboembolism, hospitalization, and death, but rivaroxaban did reduce thrombosis in an exploratory analysis.

The trial was terminated early because of underenrollment; however, the data did not appear to support routine antithrombotic prophylaxis in nonhospitalized patients with symptomatic COVID-19, advised the Feinstein Institutes.

Despite pandemic-related logistical challenges, the PREVENT-HD’s model allowed for 100% follow-up of all patients through day 49. Additionally, the remote design allowed for more diverse patient populations to enroll, with approximately 30% of the trial’s participants identifying as non-White. 

Mark Goldin, MD, Principal Investigator of the study and Northwell’s Codirector of Anticoagulation Services and Director of Clinical Trials in the Department of Medicine, stated in the press release, “While the trial was unable to show benefit with low-dose rivaroxaban to prevent adverse events that included clotting, hospitalization, and death, it contributed valuable insights for the management of outpatients with COVID-19 and coexisting cardiovascular risk factors. Northwell is a leading center worldwide in elucidating blood clot prevention strategies in COVID-19 patients during the full continuum of care: hospital admission, after hospital discharge and in the community.”

Kevin J. Tracey, MD, President and CEO of the Feinstein Institutes and Karches Family Distinguished Chair in Medical Research, stated, “Despite everything we now know about COVID-19, major questions remain about why it can cause dangerous blood clots. Drs. Spyropoulos and Goldin’s important work into novel clinical trials serves as a model for conducting impactful research, even during a global pandemic.”

Dr. Spyropoulos has collaborated with investigators across the globe, particularly during the pandemic, to study clots in COVID-19 patients.

During a late-breaking clinical trial presentation at the 2022 American Heart Association’s Scientific Sessions held November 5-7 in Chicago, Illinois, Dr. Spyropoulos shared 5-year data from a large clinical trial that Dr. Goldin and he led. As announced by Northwell Health, the trial showed the effectiveness of a new digital tool, called IMPROVE-DD VTE, that assesses and decreases the risks of these blood clots—both during hospitalization and postdischarge period—as well as provide life-saving preventative therapy.

As announced by Feinstein Institutes in August 2021, the results from the HEP-COVID clinical trial revealed that prophylaxis with therapeutic low-dose heparin significantly reduced major thromboembolism and death in high-risk hospitalized patients versus standard-of-care thromboprophylaxis. The HEP-COVID findings were published by Drs. Spyropoulos and Goldin in Journal of American Medical Association’s JAMA Internal Medicine (2021;181:1612-1620).