Very small early-terminated underpowered PrEP RCT with 64/61 HCQ/control patients and only 8 infections, HCQ infection rate 6.3% versus control 6.6%, RR 0.95 [0.25 - 3.64].
There was no hospitalization or death, no significant difference in QTc, no severe adverse events, no cardiac events (e.g., syncope and arrhythmias) observed. Medication adherence was 81%. Therapeutic levels of HCQ may not have been reached by the time of the infection in the first week.
2 infections were reported to be after discontinuation of the medication, but the authors do not specify which arm these were in. Hypothetically, if these were both in the HCQ arm, the resulting RR for treatment would be much lower.
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risk of case, 5.0% lower, RR 0.95, p = 1.00, treatment 4 of 64 (6.2%), control 4 of 61 (6.6%), NNT 325.
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Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
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Abella et al., 30 Sep 2020, Randomized Controlled Trial, USA, peer-reviewed, 18 authors, study period 9 April, 2020 - 14 July, 2020, PATCH trial.
Efficacy and Safety of Hydroxychloroquine vs Placebo for Pre-exposure SARS-CoV-2 Prophylaxis Among Health Care Workers
MD, MPhil Benjamin S Abella, BA Eliana L Jolkovsky, MPH Barbara T Biney, MD Julie E Uspal, MD, PhD Matthew C Hyman, MD Ian Frank, PhD Scott E Hensley, MD, PhD Saar Gill, MD Dan T Vogl, MSCE Ivan Maillard, MD, PhD Daria V Babushok, MD Alexander C Huang, PhD Sunita D Nasta, MD Jennifer C Walsh, E Paul Wiletyo, PhD; Phyllis A Gimotty, MD Michael C Milone, PhD Ravi K Amaravadi
JAMA Internal Medicine, doi:10.1001/jamainternmed.2020.6319
and the Prevention and Treatment of COVID-19 With Hydroxychloroquine (PATCH) Investigators 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.
Serological testing for the presence of anti-spike protein RBD IgM and IgG and nucleocapsid protein IgG (eTable 3 in Supplement 3) demonstrated that only 2 participants had anti-nucleocapsid IgG at baseline. Both participants had a negative SARS-CoV-2 RT-P CR test result, and these participants did not possess anti-spike protein RBD IgG at baseline. At the end of the 8 weeks, there were more positive participants treated with hydroxychloroquine (4 [7.4%]) compared with placebo (2 [3.7%]) who had an IgG antibody against SARS-CoV-2 (P = .40). All participants who developed antibodies also converted to SARS-CoV-2 positive status (eTable 4 in Supplement 3). At least 1 dose of study medication was taken by 65 participants in each arm; therefore, these participants were evaluable for adverse events (Table 3 ). The mean (SD) percentage of total pill counts prescribed that were actually taken during study treatment was 97% (8%) (hydroxychloroquine) and 98% (4%) (placebo). No participants in this study experienced grade 3 or 4 adverse events on the Common Toxicity Criteria for Adverse Events scale, hospitalizations, or death. However, there was a significant increase in any adverse events in the hydroxychloroquine arm vs placebo (45% vs 26%; P = .03), with increased diarrhea in participants receiving hydroxychloroquine compared with placebo (32% vs 12%; P = .01). No cardiac events (eg, syncope and arrhythmias) were observed. There was no significant difference in the median of..
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