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

ObjectivesTo 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.DesignMulticentre, 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.Setting9 hospitals across India.ParticipantsHealthcare 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).InterventionParticipants 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 outcomeProportion of laboratory-confirmed COVID-19 in the 6 months after randomisation.ResultsParticipants 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 relevanceHydroxychloroquine 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 numberCTRI/2020/05/025067.

Repurposed drug studies on the primary prevention of SARS-CoV-2 infection during the pandemic: systematic review and meta-analysis

“…Since HCQ has proven to be able to prevent SARS-CoV-2 infection in vitro,31 32 a number of clinical trials and observational studies embarked on evaluating HCQ as prophylaxis to contain SARS-CoV-2 in the human body. Most of these studies reported non-significant associations between HCQ prophylaxis and reduced SARS-CoV-2 infection rate,15 19 21 33–50 while only a few reported HCQ prophylaxis could significantly decrease SARS-CoV-2 infection rate 51–59. Our findings of significant association between PrEP use of HCQ and reduced risk of SARS-CoV-2 infection in clinical trials are consistent with another meta-analysis of cohort studies among high-risk HCWs performed by Stricker and Fesler 60.…”

COVID-19 patients’ clinical profile and outcome with respect to their vaccination status: A prospective observational multicentre cohort study during third wave in Western India

“…We don't have an effective pharmacological preventive therapy for a COVID-19 outbreak even though it has been more than a two years since the pandemic begun. Hydroxychloroquine was recommended by the Indian Council of Medical Research (ICMR) as a pre-exposure prophylaxis without substantial clinical studies and was found to be ineffective [ 4 , 5 ]. Remdesivir has shown benefit in reduction of disease progression by 87% in high risk patients if given within 3–5 days of symptom onset [ 6 ].…”

“…Remdesivir has shown benefit in reduction of disease progression by 87% in high risk patients if given within 3–5 days of symptom onset [ 6 ]. Non-pharmacological measures like wearing a mask, social distancing and hand hygiene proved to be useful in controlling the spread of infection [ 5 ]. COVID-19 vaccination has proved beneficial in reducing hospitalization and mortality from COVID-19 across various countries [ 7 , 8 ].…”

Failed Repurposing of Lysosomotropic Drugs for COVID-19 Treatment or Prevention

“…Tummino et al [3] established that the threshold concentration for inducing phospholipidosis in cultured cells is correlated to the antiviral activity. Several drugs from the list, including chloroquine, hydroxycholoquine and amiodarone, have been investigated in clinical trials for COVID-19 treatment or prevention, but without success [2,3,[7][8][9][10][11].…”