Heparin is typically administered for blood clotting, but its anti-inflammatory and anti-viral effects have captured interest as a potential COVID-19 treatment. An international team of researchers led by Peter Jüni of St. Michael’s Hospital and the University of Toronto in Canada conducted a study to look at the effectiveness of heparin in treating moderate and severe COVID-19 infection.
Results from the RAPID clinical trial suggest heparin may lower the risk of death from moderate COVID-19 infection by 78%. Heparin also significantly increased the number of days patients went without ventilation or requiring organ support.
The study authors write:
“Taken together, these trials provide conclusive evidence for the benefit of therapeutic heparin in moderately ill ward patients with Covid-19 irrespective of D-dimer levels, but not in severely ill ICU patients.”
The study “Heparin for Moderately Ill Patients with Covid-19” was published on the preprint medRxiv* server.
Clinical trial information
The RAPID clinical trial took place in 28 sites across six countries from May 29, 2020, to April 12, 2021. The researchers recruited 465 hospitalized patients with COVID-19 and elevated D-dimer levels within the first five days of admission. Patients were excluded from the study if they had substantial bleeding, a contraindication against heparin anticoagulation, were pregnant, or were already close to death.
Patients were randomly given either a therapeutic or prophylactic heparin for 28 days or until the patient was discharged from the hospital or died. Treatment continued even if a patient was admitted to the ICU.
The average patient age was 60 years. More than half (56.8%) of patients were men, and the average patient was overweight, according to their BMI.
A total of 228 patients received the therapeutic heparin and 237 patients received dose-capped prophylactic subcutaneous heparin.
It took an average of 7.1 days for patients to experience symptoms and later admit themselves to the hospital. People given therapeutic heparin stayed on treatment for an average of 6.5 days. In contrast, the prophylactic heparin group stayed on treatment for 6.3 days.
About 16.2% of patients given therapeutic heparin and 21.9% of prophylactic heparin experienced either ICU admission, mechanical ventilation, or death within 28 days of hospital admission.
Death from any cause —with hypoxic respiratory failure being the most common cause of death — happened in 1.8% of patients with therapeutic heparin and 7.6% with prophylactic heparin.
People were unventilated for an average of 26.5 days with therapeutic heparin and prophylactic heparin. About 9.2% of patients in the therapeutic heparin group and 11% of patients in the prophylactic heparin group were put on a ventilator.
Patients were ICU-free for about 26 days when given therapeutic heparin versus the 24.1 ICU-free days experienced by the prophylactic heparin group. About 14.5% to 17.7% of patients required ICU admission.
Benefits of therapeutic heparin
The researchers conducted a meta-analysis of different trials, including the RAPID study, that evaluated heparin treatment for patients with COVID-19.
The results showed no significant decrease in death of any cause. However, treatment with therapeutic heparin was linked to significant reductions in the composite of death or invasive mechanical ventilation, organ support, and major thrombotic events.
Therapeutic heparin increased the number of ventilator-free and organ support-free days.
Two patients in the therapeutic heparin group and four patients in the prophylactic heparin group had major bleeding. While the researchers observed more bleeding with heparin, this was considered non-significant. There were no fatal bleeding or cases of intracranial hemorrhages.
These effects were more pronounced with patients with moderate COVID-19 infection than patients with severe infection admitted into the ICU.
“The RAPID trial did not find a significant reduction in the primary composite outcome of death, mechanical ventilation or ICU admission with therapeutic heparin. However, in conjunction with the multiplatform trial, it suggests a clinical benefit of therapeutic heparin in moderately ill ward patients with Covid-19,” concluded the research team.
The RAPID trial had an adaptive design in which patient recruitment would only increase if the conditional power at 75% of the original sample size were between 60 and 80%. Because the conditional power was 60%, the study was underpowered with a small sample size.
medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.