Enoxaparin prophylaxis against thrombotic events was not effective among at-risk outpatients with COVID-19, according to the results of the phase 3b ETHIC trial published in Lancet Hematology.

An increased risk of thromboembolic complications is associated with COVID-19. Hospitalized and non-critically ill patients with COVID-19 are commonly treated with prophylactic low-molecular-weight heparin (LMWH). The aim of this study was to determine if enoxaparin, an LMWH, could reduce the risk of thromboembolic complications among outpatients with COVID-19.

The multicenter, open-label phase 3b ETHIC trial randomly assigned 219 patients with symptomatic COVID-19 to receive enoxaparin for 21 days or no enoxaparin, which was the standard of care. Patients had not received the COVID-19 vaccine and had at least 1 risk factor for severe disease. The primary endpoint was a composite of all-cause hospitalization and all-cause mortality at 21 days. Secondary endpoints included venous thromboembolism and bleeding events.

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The planned enrollment was 1370 patients; however, the trial was terminated early due to slow enrollment and thromboembolic rate that was lower than expected.

At baseline, the median age was 59 and 44% of patients were women. There were 65% of patients who were White, 28% who were Asian, and 7% who were Black, mixed race, Arab, or Middle Eastern. The median body mass index was 29.5 kg/m3 and 72% of patients were never smokers and 8.5% were current smokers. The median time from symptom onset and COVID-19 diagnosis to randomization was 5 and 2 days, respectively. The most common risk factors for severe COVID-19 disease in the cohort was hypertension, diabetes, vascular disease, and chronic lung disease.

The composite endpoint was similar between groups, with 11% of patients in the enoxaparin and standard of care groups hospitalized or died (hazard ratio [HR], 1.09; 95% CI, 0.49-2.43; P =.83). In each group, all-cause hospitalization was 11% and venous thromboembolism occurred in 1%.

Bleeding events were uncommon, with 2% and 1% of patients experiencing bleeding in the enoxaparin and standard of care groups, respectively.

Adverse events occurred more frequently in the enoxaparin group (21%) compared with the standard of care group (11%), with pneumonia being the most common event. There were 13 adverse events that led to early discontinuation of enoxaparin and there was 1 death in the enoxaparin group with an unknown cause.

The authors concluded that “these results suggest that early anticoagulation for the prevention of thromboembolic complications in non-critical outpatients with COVID-19 might have no clinical benefit and should not be used routinely in this clinical setting.”

Disclosures: This study was supported in part by Sanofi UK. Please see the original reference for a full list of disclosures.


Cools F, Virdone S, Sawhney J, et al. Thromboprophylactic low-molecular-weight heparin versus standard of care in unvaccinated, at-risk outpatients with COVID-19 (ETHIC): an open-label, multicentre, randomised, controlled, phase 3b trial. Lancet Hematol. Published online June 29, 2022. doi: 10.1016/S2352-3026(22)00173-9