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HCQ study #146 of 320   Meta Analysis
9/21 Pre-Exposure Prophylaxis study (treated before exposed to the virus)
Rajasingham et al., medRxiv, doi:10.1101/2020.09.18.20197327 (Peer Reviewed)
Hydroxychloroquine as pre-exposure prophylaxis for COVID-19 in healthcare workers: a randomized trial
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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. Trial halted due to low enrollment. US prescriptions only stopped briefly, resuming in June, so the authors can complete the study [1].
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 placebo for the first 3 weeks. The effect may be greater with a dosage regimen that achieves therapeutic levels faster [2]. ~40% of participants suspected they might have had COVID-19 before the trial, the effect in people without prior COVID-19 may be higher.
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 EC50
Internet 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).

Rajasingham et al., 9/21/2020, Randomized Controlled Trial, USA, North America, peer-reviewed, 22 authors.
risk of hospitalization, 50.1% lower, RR 0.50, p = 1.00, treatment 1 of 989 (0.1%), control 1 of 494 (0.2%).
risk of COVID-19 case, 27.0% lower, RR 0.73, p = 0.12, treatment 58 of 989 (5.9%), control 39 of 494 (7.9%).

Effect extraction follows pre-specified rules prioritizing more serious outcomes. For an individual study the most serious outcome may have a smaller number of events and lower statistical signficance, however this provides the strongest evidence for the most serious outcomes when combining the results of many trials.
All 320 studies   Meta Analysis
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