COVID-19 is marked by increased inflammation and abnormal clotting in blood vessels, especially the lungs, and is thought to contribute to progression to serious illness and death. New trial results show that administering a full dose of a standard anticoagulant to early to moderately ill hospitalized patients with COVID-19 could stop the process of thrombo-inflammation and reduce the risk of severe disease and death.
The study, led by researchers at St. Michael’s Hospital, a site of Unity Health Toronto, and the University of Vermont’s Larner College of Medicine, is available in preview on MedRxiv.
Heparin – a blood thinner given regularly in low doses to hospital patients – prevents blood clots and reduces inflammation. “This study was designed to detect a difference in the primary outcome that included transfer to intensive care, mechanical ventilation, or death,” says Mary Cushman, MD, M.Sc., co-principal investigator of the study and professor of medicine at the University of Vermont. Larner College of Medicine.
The international randomized open-label multicenter RAPID trial (also known as the RAPID COVID COAG trial – RAPID Trial) examined the benefits of administering a full therapeutic dose of heparin over a low-dose prophylactic to patients moderately ill admitted to hospital wards with COVID-19.
The primary outcome measure was a composite of ICU admission, mechanical ventilation, or death up to 28 days. Safety results included major bleeding. The primary outcome measure occurred in 37 of 228 patients (16.2%) with full-dose therapeutic heparin, and 52 of 237 (21.9%) with low-dose heparin (odds ratio [OR], 0.69; 95% confidence interval [CI], 0.43-1.10; p = 0.12). Four patients (1.8%) on therapeutic heparin died compared to 18 (7.6%) on prophylactic heparin (OR, 0.22; 95% CI, 0.07-0.65).
âAlthough we found that therapeutic heparin did not statistically significantly reduce the incidence of the primary composite of death, mechanical ventilation or admission to intensive care compared to low-dose heparin, the risks of deaths from all causes were significantly reduced by 78% with therapeutic heparin âsays first author and co-principal investigator Michelle Sholzberg, MDCM, M.Sc., head of the hematology-oncology division, medical director of the laboratory coagulation clinic at St. Michael’s Hospital of Unity Health Toronto and Assistant Professor at the University of Toronto.
Peter JÃ¼ni, MD, co-principal investigator, director of the Applied Health Research Center (AHRC) in St. Michael’s and professor of medicine at the University of Toronto, says the researchers also presented a meta-analysis of randomized evidence (including data from a large multiplatform trial of ATTACC, ACTIV-4a and REMAP-CAP), which clearly indicated that therapeutic heparin is beneficial in moderately ill hospitalized COVID-19 patients. He adds that an additional meta-analysis presented in the prepublication showed therapeutic heparin to be beneficial in moderately ill hospitalized patients, but not in critically ill intensive care patients.
Another unique aspect of the RAPID trial was its funding mechanism – a sort of grassroots effort in which support was garnered through Defense Research and Development Canada, the St. Michael, from the St. Joseph Health Care Foundation, participating institutional grants and even a GoFundMe campaign, among other sources.
“We called this trial ‘The Little Engine That Could’ because of the willingness of investigators around the world to conduct it,” Cushman said.
Sholzberg said: “We believe the results of our trial and the multiplatform trial taken together should lead to a change in clinical practice for moderately ill patients with COVID-19.”
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