Efficacy and Safety of Inhaled Ethanol in Early-Stage SARS-CoV-2 Infection in Older Adults: A Phase II Randomized Clinical Trial

Abstract

Background: Inhaled ethanol in the early stages of SARS-CoV-2 infection may reduce the viral load, decreasing progression and improving prognosis. The ALCOVID-19 trial was designed to study the efficacy and safety of inhaled ethanol in older adults at initial phases of infection.

Methods: Randomized, triple-blind, placebo-controlled phase II clinical trial. Experimental group (n = 38) inhaled 65° ethanol through an oxygen flow, while in the control group (n = 37), water for injection was used. General endpoint was to evaluate disease progression according to the modified World Health Organization (WHO) Clinical Progression Scale. Specific effectiveness endpoints were body temperature, oxygen saturation, viral load assessed by cycle threshold (Ct) on real-time polymerase chain reaction (RT-PCR), analytical biomarkers and use of antibiotics or corticosteroids. Specific safety outcomes were the absence of ethanol in plasma, electrographic, analytical, or respiratory alterations.

Results: In the intention-to-treat population, no differences were found regarding disease progression. Mean Ct values increased over time in both groups, being numerically higher in the ethanol group, reaching a value above 33 only in the ethanol group on day 14, a value above which patients are considered non-infective. No differences were found in the other specific effectiveness endpoints. Inhaled ethanol was proven to be safe as no plasma ethanol was detected, and there were no electrocardiographic, analytical, or respiratory alterations.

Conclusions: The efficacy of inhaled ethanol in terms of the progression of SARS-CoV-2 infection was not demonstrated in the present trial. However, it is positioned as a safe treatment for elderly patients with early-stage COVID-19.

Keywords: COVID-19; SARS-CoV-2; elderly; inhaled ethanol; randomized controlled trial.

Figure 1

Trial design: study visits, collected variables and administration of the study medication. ECG: electrocardiogram. Created with BioRender.com.

Figure 2

Trial flow chart showing patient enrollment, group allocation and deaths.

Figure 3

Cumulative relative frequency (%) of patients in both treatment groups who progress according to the modified WHO Clinical Progression Scale. Percentages were calculated based on the populations of each group (n = 38 in ethanol group and n = 37 in placebo group).

Figure 4

Cycle threshold (Ct) values of the three genes (N, E and RdRP) up to visit on day 14. Mean is represented by a red cross, median is represented by the horizontal line contained in the box, and the first and third quartiles by the lower and upper limits of the box, respectively. The mean Ct values at each visit are linked together by a dashed line for each of the groups.

Figure 5

Cycle threshold (Ct) values oh the N gene up to visit on day 14. Mean is represented by a red cross, median is represented by the horizontal line contained in the box, and the first and third quartiles by the lower and upper limits of the box, respectively. The mean Ct values at each visit are linked together by a dashed line for each of the groups.