According to research published in The Lancet Haematology, thromboprophylaxis with enoxaparin does not appear to reduce early hospitalizations and deaths among outpatients with symptomatic COVID-19.

The researchers investigated whether thromboprophylaxis with enoxaparin would prevent hospitalization and death in symptomatic, but clinically stable, outpatients with COVID-19 ( Identifier: NCT04400799)

The randomized, open-label, parallel-group, investigator-initiated, phase 3 trial, OVID, was conducted at 8 centers in Switzerland and Germany. The study included outpatients (≥50 years of age) with acute COVID-19 with respiratory symptoms or body temperature higher than 37.5°C. Between August 15, 2020, and January 14, 2022, eligible participants were stratified by age (50-70 years vs older than 70 years) and study center and randomly assigned (1:1) to receive either subcutaneous enoxaparin (40 mg) once daily for 14 days or standard of care (no thromboprophylaxis).

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The study’s primary efficacy and safety outcomes were a composite of any hospitalization and all-cause death within 30 days of randomization (in the intention-to-treat population) and major bleeding, respectively.

A total of 472 outpatients were randomly assigned to receive enoxaparin (n=234) or standard of care (n=238). The median age was 57 years (interquartile range, 53-62), and the group was 54% male and 46% female.

The researchers demonstrated that the 30-day risk of the primary outcome was similar in the enoxaparin and control groups (3% vs 3%; adjusted relative risk, 0.98; 95% CI, 0.37-2.56; P =.96). They reported that all hospitalizations were related to COVID-19, and no deaths or major bleeding events occurred during the study.

At the predefined formal interim analysis for efficacy, an independent Data Safety Monitoring Board recommended early termination of the trial due to a very low probability of enoxaparin showing superiority of thromboprophylaxis for the primary outcome under the initial study design assumptions and predefined statistical criteria.

“These findings from an individual multinational, randomized, controlled, phase 3 trial on low-molecular-weight heparin, together with those from a published trial on the direct oral anticoagulant apixaban, do not support the routine use of anticoagulants in outpatients with COVID-19, as it might not prevent clinical deterioration in terms of hospitalizations related to COVID-19,” concluded the researchers.

Limitations of the study included the open-label design and lack of a placebo-controlled group, lack of external adjudication for primary outcome events, variable surges of SARS-CoV-2 variants over time, only 30 days of postenrollment data available, underrepresentation of older patients, and consequent low event rates.

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures. 


Barco S, Voci D, Held U, et al. Enoxaparin for primary thromboprophylaxis in symptomatic outpatients with COVID-19 (OVID): a randomised, open-label, parallel-group, multicentre, phase 3 trial. Lancet Haematol. Published online June 19, 2022. doi:10.1016/S2352-3026(22)00175-2