Antithrombotic prophylaxis of no benefit in symptomatic outpatients with COVID-19: Lancet

Based on the trial, the researchers found the following:

· Following the advice of the Data and Safety Monitoring Board, this study was terminated early due to slow enrolment and a lower-than-expected event rate.

· 230 patients with COVID-19 were assessed for eligibility, of whom 219 were enrolled between Oct 27, 2020, and Nov 8, 2021, and randomly assigned to receive standard of care (n=114) or enoxaparin(n=105).

· 44% patients were women, 56% were men, and one patient had missing sex data.

· 65% of 218 participants with data on race and ethnicity were White, 28% were Asian, and 7% were Black, mixed race, or Arab or Middle Eastern. Median follow-up in both groups was 21 days.

· There was no difference in the composite of all-cause mortality and hospitalisation at 21 days between the enoxaparin group (12 of 105 patients) and the standard-of-care group (12 of 114 patients; unadjusted hazard ratio 1·09).

· At 21 days, two of 105 patients in the enoxaparin group (one minor bleed and one bleed of unknown severity) and one of 114 patients in the standard-of-care group (major abnormal uterine bleeding) had a bleeding event.

· 21% patients in the enoxaparin group and 11% patients in the standard-of-care group had adverse events.

· The most common adverse event in both groups was COVID-19-related pneumonia (6% patients in the enoxaparin group and 4% patients in the standard-of-care group).

· One patient in the enoxaparin group died and their cause of death was unknown.

Findings from the ETHIC trial indicated that prophylaxis with low-molecular-weight heparin was not beneficial for at-risk outpatients with COVID-19. The trial although terminated early, "the data combined with data from similar studies, provide further insights to influence clinical practice and inform international guidelines," the researchers wrote in their study. 

Based on the trial, the researchers found the following:

· At the predefined formal interim analysis for efficacy (50% of total study population), the independent Data Safety Monitoring Board recommended early termination of the trial on the basis of predefined statistical criteria having considered the very low probability of showing superiority of thromboprophylaxis with enoxaparin for the primary outcome under the initial study design assumptions.

· Between Aug 15, 2020, and Jan 14, 2022, from 3319 participants prescreened, 472 were included in the intention-to-treat population and randomly assigned to receive enoxaparin (n=234) or standard of care (n=238). The median age was 57 years (IQR 53–62) and 46% were women.

· The 30-day risk of the primary outcome was similar in participants allocated to receive enoxaparin and in controls (8 of 234 vs 8 of 238; adjusted relative risk 0·98).

· All hospitalisations were related to COVID-19.

· No deaths were reported during the study.

· No major bleeding events were recorded.

· Eight serious adverse events were recorded in the enoxaparin group versus nine in the control group.

"These findings indicate that thromboprophylaxis with enoxaparin does not reduce early hospitalisations and deaths among outpatients with symptomatic COVID-19," the researchers wrote in their study.

"Owing to under-representation of older patients and consequent low event rates, futility of the treatment under the initial study design assumptions could not be conclusively assessed," they concluded.

To sum up the findings from two trials, the routine use of antithrombotic therapies to prevent thromboembolic complications provided no benefit for symptomatic outpatients with COVID-19. 

Reference:

1) The Lancet Haematology

Source Reference: Cools F, 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 Haematol 2022; DOI: 10.1016/S2352-3026(22)00173-9.

2) The Lancet Haematology

Source Reference: Barco S, 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 2022; DOI: 10.1016/S2352-3026(22)00175-2.