Hydroxychloroquine plus personal protective equipment versus personal protective equipment alone for the prevention of laboratory-confirmed COVID-19 infections among healthcare workers: a multicentre, parallel-group randomised controlled trial from India

Abstract

Objectives: To determine whether hydroxychloroquine when used with personal protective equipment reduces the proportion of laboratory-confirmed COVID-19 among healthcare workers in comparison to the use of personal protective equipment alone.

Design: Multicentre, parallel-group, open-label randomised trial. Enrolment started on 29 June 2020 and stopped on 4 February 2021. Participants randomised in HydrOxychloroquine Prophylaxis Evaluation were followed for 6 months.

Setting: 9 hospitals across India.

Participants: Healthcare workers in an environment with exposure to COVID-19 were randomised in a 1:1 ratio to hydroxychloroquine plus use of personal protective equipment or personal protective equipment alone. 886 participants were screened and 416 randomised (213 hydroxychloroquine arm and 203 personal protective equipment).

Intervention: Participants in intervention arm received 800 mg of hydroxychloroquine on day of randomisation and then 400 mg once a week for 12 weeks in addition to the use of personal protective equipment. In the control arm, participants continued to use personal protective equipment alone.

Main outcome: Proportion of laboratory-confirmed COVID-19 in the 6 months after randomisation.

Results: Participants were young (mean age 32.1 years, SD 9.1 years) with low-comorbid burden. 47.4% were female. In the 6 months after randomisation (primary analysis population=413), 11 participants assigned to the hydroxychloroquine group and 12 participants assigned to the standard practice group met the primary endpoint (5.2% vs 5.9%; OR 0.85, 95% CI 0.35 to 2.07, p=0.72). There was no heterogeneity of treatment effect in any prespecified subgroup. There were no significant differences in the secondary outcomes. The adverse event rates were 9.9% and 6.9% in the hydroxychloroquine and standard practice arms, respectively. There were no serious adverse events in either group.

Conclusions and relevance: Hydroxychloroquine along with personal protective equipment was not superior to personal protective equipment alone on the proportion of laboratory-confirmed COVID-19. Definitive conclusions are precluded as the trial stopped early for futility, and hence was underpowered.

Trial registration number: CTRI/2020/05/025067.

Keywords: COVID-19; clinical pharmacology; public health.

Figure 1

Consolidated Standards of Reporting Trials (CONSORT) flow diagram.

Figure 2

Forest plot for subgroup analysis of laboratory-confirmed COVID-19 infection within 6 months after randomisation. Intervention versus control: number of patients with events/total number of patients, p value is for interaction effect.