Hydroxychloroquine as pre-exposure prophylaxis for COVID-19 in healthcare workers: a randomized trial
et al., medRxiv, doi:10.1101/2020.09.18.20197327, COVID PREP, NCT04328467 (history)
, Hydroxychloroquine as pre-exposure prophylaxis for COVID-19 in healthcare workers: a randomized trial, medRxiv, doi:10.1101/2020.09.18.20197327, COVID PREP, NCT04328467
PrEP RCT showing HR 0.73, p = 0.12. Trial halted after 47% enrollment, p < 0.05 will be reached at ~75% enrollment if similar results continue.HR 0.66/0.68 for full medication adherence, 0.72/0.74, p = 0.18/0.22 overall (1x/2x dosing). Efficacy for first responders was higher, OR 0.32, p = 0.01. First responders had a much higher incidence, allowing greater power, and reducing the effect of confounders such as misdiagnosis of other conditions or survey issues.Performance is similar to the control arm for the first 3 weeks. The effect may be greater with a dosage regimen that achieves therapeutic levels faster [tandfonline.com]. ~40% of participants suspected they might have had COVID-19 before the trial, the effect in people without prior COVID-19 may be higher.Research shows the treatment used in the control arm (folic acid) may have significant efficacy for COVID-19 [Deschasaux-Tanguy, Farag], so the true effectiveness of HCQ may be higher than observed. Also see [acpjournals.org].Authors note:- the trial was underpowered
- investigation into more frequent dosing may be warranted
- insufficient dosing with no participants achieving more than the in vitro EC50Internet survey RCT subject to survey bias. There were no deaths or ICU admissions. Low risk healthcare workers, median age ~40. 494 1x/week dosing, 495 2x/week dosing, 494 control participants (1x and 2x participants received the same overall dosage). COVID PREP. NCT04328467 (history).
- investigation into more frequent dosing may be warranted
- insufficient dosing with no participants achieving more than the in vitro EC50Internet survey RCT subject to survey bias. There were no deaths or ICU admissions. Low risk healthcare workers, median age ~40. 494 1x/week dosing, 495 2x/week dosing, 494 control participants (1x and 2x participants received the same overall dosage). COVID PREP. NCT04328467 (history).
2.
Deschasaux-Tanguy et al., BMC Medicine, doi:10.1186/s12916-021-02168-1,
Nutritional risk factors for SARS-CoV-2 infection: a prospective study within the NutriNet-Santé cohort,
https://link.springer.com/article/..6/s12916-021-02168-1/fulltext.html.
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risk of hospitalization, 50.1% lower, RR 0.50, p = 1.00, treatment 1 of 989 (0.1%), control 1 of 494 (0.2%), NNT 987.
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risk of case, 27.0% lower, HR 0.73, p = 0.12, treatment 58 of 989 (5.9%), control 39 of 494 (7.9%), NNT 49.
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| Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates |
Rajasingham et al., 21 Sep 2020, Randomized Controlled Trial, USA, peer-reviewed, 22 authors, this trial compares with another treatment - results may be better when compared to placebo, trial NCT04328467 (history) (COVID PREP).
Hydroxychloroquine as Pre-exposure Prophylaxis for Coronavirus Disease 2019 (COVID-19) in Healthcare Workers: A Randomized Trial
Clinical Infectious Diseases, doi:10.1093/cid/ciaa1571
Background. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a rapidly emerging virus causing the ongoing coronavirus disease 2019 (COVID-19) pandemic with no known effective prophylaxis. We investigated whether hydroxychloroquine could prevent SARS-CoV-2 in healthcare workers at high risk of exposure. Methods. We conducted a randomized, double-blind, placebo-controlled clinical trial of healthcare workers with ongoing exposure to persons with SARS-CoV-2, including those working in emergency departments, intensive care units, COVID-19 hospital wards, and first responders. Participants across the United States and in the Canadian province of Manitoba were randomized to hydroxychloroquine loading dose then 400 mg once or twice weekly for 12 weeks. The primary endpoint was confirmed or probable COVID-19-compatible illness. We measured hydroxychloroquine whole-blood concentrations. Results. We enrolled 1483 healthcare workers, of whom 79% reported performing aerosol-generating procedures. The incidence of COVID-19 (laboratory-confirmed or symptomatic compatible illness) was 0.27 events/person-year with once-weekly and 0.28 events/person-year with twice-weekly hydroxychloroquine compared with 0.38 events/person-year with placebo. For once-weekly hydroxychloroquine prophylaxis, the hazard ratio was .72 (95% CI, .44-1.16; P = .18) and for twice-weekly was .74 (95% CI, .46-1.19; P = .22) compared with placebo. Median hydroxychloroquine concentrations in whole blood were 98 ng/mL (IQR, 82-120) with onceweekly and 200 ng/mL (IQR, 159-258) with twice-weekly dosing. Hydroxychloroquine concentrations did not differ between participants who developed COVID-19-compatible illness (154 ng/mL) versus participants without COVID-19 (133 ng/mL; P = .08). Conclusions. Pre-exposure prophylaxis with hydroxychloroquine once or twice weekly did not significantly reduce laboratoryconfirmed COVID-19 or COVID-19-compatible illness among healthcare workers. clinical Trials Registration. NCT04328467.
Supplementary Data Supplementary materials are available at Clinical Infectious Diseases online. Consisting of data provided by the authors to benefit the reader, the posted materials are not copyedited and are the sole responsibility of the authors, so questions or comments should be addressed to the corresponding author.
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