Efficacy and Safety of Hydroxychloroquine vs Placebo for Pre-exposure SARS-CoV-2 Prophylaxis Among Health Care Workers

Abstract

IMPORTANCE Health care workers (HCWs) caring for patients with coronavirus disease 2019 (COVID-19) are at risk of exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Currently, to our knowledge, there is no effective pharmacologic prophylaxis for individuals at risk. OBJECTIVE To evaluate the efficacy of hydroxychloroquine to prevent transmission of SARS-CoV-2 in hospital-based HCWs with exposure to patients with COVID-19 using a pre-exposure prophylaxis strategy. DESIGN, SETTING, AND PARTICIPANTS This randomized, double-blind, placebo-controlled clinical trial (the Prevention and Treatment of COVID-19 With Hydroxychloroquine Study) was conducted at 2 tertiary urban hospitals, with enrollment from April 9, 2020, to July 14, 2020; follow-up ended August 4, 2020. The trial randomized 132 full-time, hospital-based HCWs (physicians, nurses, certified nursing assistants, emergency technicians, and respiratory therapists), of whom 125 were initially asymptomatic and had negative results for SARS-CoV-2 by nasopharyngeal swab. The trial was terminated early for futility before reaching a planned enrollment of 200 participants. INTERVENTIONS Hydroxychloroquine, 600 mg, daily, or size-matched placebo taken orally for 8 weeks. MAIN OUTCOMES AND MEASURES The primary outcome was the incidence of SARS-CoV-2 infection as determined by a nasopharyngeal swab during the 8 weeks of treatment. Secondary outcomes included adverse effects, treatment discontinuation, presence of SARS-CoV-2 antibodies, frequency of QTc prolongation, and clinical outcomes for SARS-CoV-2-positive participants. RESULTS Of the 132 randomized participants (median age, 33 years [range, 20-66 years]; 91 women [69%]), 125 (94.7%) were evaluable for the primary outcome. There was no significant difference in infection rates in participants randomized to receive hydroxychloroquine compared with placebo (4 of 64 [6.3%] vs 4 of 61 [6.6%]; P > .99). Mild adverse events were more common in participants taking hydroxychloroquine compared with placebo (45% vs 26%; P = .04); rates of treatment discontinuation were similar in both arms (19% vs 16%; P = .81). The median change in QTc (baseline to 4-week evaluation) did not differ between arms (hydroxychloroquine: 4 milliseconds; 95% CI, −9 to 17; vs placebo: 3 milliseconds; 95% CI, −5 to 11; P = .98). Of the 8 participants with positive results for SARS-CoV-2 (6.4%), 6 developed viral symptoms; none required hospitalization, and all clinically recovered. CONCLUSIONS AND RELEVANCE In this randomized clinical trial, although limited by early termination, there was no clinical benefit of hydroxychloroquine administered daily for 8 weeks as pre-exposure prophylaxis in hospital-based HCWs exposed to patients with COVID-19. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT04329923

Prophylactic use of Hydroxychloroquine among Physicians working in Pandemic Hospitals

“…Only one physician out of 11 who reported diarrhea had COVID infection. A recent randomized controlled study on HQN prophylaxis among healthcare workers, reported no signi cant difference in terms of infection rates, in parallel with our results [12]. In the same study, it was reported that 20% of 65 patients developed diarrhea during HQN prophylaxis.…”

The efficacy and safety of hydroxychloroquine for COVID-19 prophylaxis: A systematic review and meta-analysis of randomized trials

“…The remaining three trials required contact with a COVID-19 patient (i.e. post-exposure prophylaxis) [ 15 , 16 , 18 ]. Thirty four percent of participants had inappropriate PPE donned during their exposures.…”

COVID-19 in patients with systemic lupus erythematosus: lessons learned from the inflammatory disease

“…233,234 Multiple recent studies, including observational data from patients with immune-mediated diseases on long-term D 1 8 3 X XHCQ as well as large randomized clinical trials, have consistently demonstrated the lack of efficacy of HCQ in preventing the viral infection or improving any COVID-19-related outcomes. 171,190,[235][236][237][238] However, for several weeks after the preclinical studies and limited observational data came to light, HCQ shortages ensued in many countries as its use was redirected toward prophylaxis or management of COVID-19, leading to inadequate supplies of the drug for many patients with SLE worldwide. 239,240 For instance, an electronic survey distributed to the SD 1 8 4 X XLE International Collaborating Clinics D 1 8 5 X Xmembers with SLE-affiliated centers aimed to evaluate physicians' experiences with D 1 8 6 X XHCQ shortages during the pandemic.…”