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COVID-19 Evidence Alerts
from McMaster PLUSTM

Current best evidence for clinical care (more info)

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Treatment, Primary Prevention Cortegiani A, Ippolito M, Ingoglia G, et al. Update I. A systematic review on the efficacy and safety of chloroquine/hydroxychloroquine for COVID-19. J Crit Care. 2020 Jul 11;59:176-190. doi: 10.1016/j.jcrc.2020.06.019.

PURPOSE: To assess efficacy and safety of chloroquine (CQ)/hydroxychloroquine (HCQ) for treatment or prophylaxis of COVID-19 in adult humans.

MATERIALS AND METHODS: MEDLINE, PubMed, EMBASE and two pre-print repositories (bioRxiv, medRxiv) were searched from inception to 8th June 2020 for RCTs and nonrandomized studies (retrospective and prospective, including single-arm, studies) addressing the use of CQ/HCQ in any dose or combination for COVID-19.

RESULTS: Thirty-two studies were included (6 RCTs, 26 nonrandomized, 29,192 participants). Two RCTs had high risk, two 'some concerns' and two low risk of bias (Rob2). Among nonrandomized studies with comparators, nine had high risk and five moderate risk of bias (ROBINS-I). Data synthesis was not possible. Low and moderate risk of bias studies suggest that treatment of hospitalized COVID-19 with CQ/HCQ may not reduce risk of death, compared to standard care. High dose regimens or combination with macrolides may be associated with harm. Postexposure prophylaxis may not reduce the rate of infection but the quality of the evidence is low.

CONCLUSIONS: Patients with COVID-19 should be treated with CQ/HCQ only if monitored and within the context of high quality RCTs. High quality data about efficacy/safety are urgently needed.

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Comments from MORE raters

Emergency Medicine rater

This registered systematic review evaluated the efficacy and safety of chloroquine and hydroxychloroquine for COVID-19. The authors included 32 studies (6 RCTs and 26 non-randomized trials) with 29,192 patients. Nine studies were pre-print. Data synthesis was not possible due to limitations in individual studies. Studies at low and moderate risk of bias suggest these medications do not reduce mortality. Studies evaluating high-dose regimens or the medications used with macrolides suggest harm. Finally, post-exposure prophylaxis does not reduce infection rates, although the evidence quality was low. In summary, most studies evaluating hydroxychloroquine and chloroquine have limitations but do not demonstrate benefit in COVID-19.

Emergency Medicine rater

This is a well-done systematic review of trials of chloroquine and hydroxychloroquine for treating COVID-19 patients. The search was exhaustive and included randomized, non-randomized, and single-arm cohort studies. 32 studies (including 6 RCTs) with a total of 29,192 studied participants were found, but only 2 studies had low risk of bias, one on treatment and one on prophylaxis. Overall, for hospitalized patients, no mortality benefit was found and some harm may be associated with the use of chloroquine/hydroxychloroquine. A more definitive answer to the question about these medications must await further better conducted trials.

General Internal Medicine-Primary Care(US) rater

There is so much noise around the use of HCQ in COVID-19. A systematic review is timely and points to the need, as always, for good randomized trials for any drug to assess efficacy.

Hospital Doctor/Hospitalists rater

A synthesis article on the use of chloroquine and hydroxychloroquine for COVID. Unfortunately, there isn't much evidence either way. This article does summarize the harms and cover the current recommendations. I would say that most of my colleagues do not know this (it would probably go without saying that Donald Trump is not one of my colleagues). I think most hospitalists have gotten away from using this completely, so I am not sure how relevant this would be to them.

Infectious Disease rater

This careful systematic review found no clear evidence of benefits and some evidence of harms from using these drugs in COVID-19 infection.

Infectious Disease rater

Very useful to have a systematic review of this controversial treatment, which seemed settled but keeps coming back up.

Intensivist/Critical Care rater

It is very important to wait for convincing data for hydroxychloroquine use in COVID-19. At this point, the potential for significant harm is equal to the potential for benefit.