Systematic review and meta-analysis of randomized trials of hydroxychloroquine for the prevention of COVID-19

Abstract

Background Recruitment into randomized trials of hydroxychloroquine (HCQ) for prevention of COVID-19 has been adversely affected by a widespread conviction that HCQ is not effective for prevention. In the absence of an updated systematic review, we conducted a meta-analysis of randomized trials that study the effectiveness of HCQ to prevent COVID-19. Methods A search of PubMed, medRxiv, and clinicaltrials.gov combined with expert consultation found 11 completed randomized trials: 7 pre-exposure prophylaxis trials and 4 post-exposure prophylaxis trials. We obtained or calculated the risk ratio of COVID-19 diagnosis for assignment to HCQ versus no HCQ (either placebo or usual care) for each trial, and then pooled the risk ratio estimates. Results The pooled risk ratio estimate of the pre-exposure prophylaxis trials was 0.72 (95% CI: 0.58–0.90) when using either a fixed effect or a standard random effects approach, and 0.72 (95% CI: 0.55–0.95) when using a conservative modification of the Hartung-Knapp random effects approach. The corresponding estimates for the post-exposure prophylaxis trials were 0.91 (95% CI: 0.72–1.16) and 0.91 (95% CI: 0.62–1.35). All trials found a similar rate of serious adverse effects in the HCQ and no HCQ groups. Discussion A benefit of HCQ as prophylaxis for COVID-19 cannot be ruled out based on the available evidence from randomized trials. However, the “not statistically significant” findings from early prophylaxis trials were widely interpreted as definite evidence of lack of effectiveness of HCQ. This interpretation disrupted the timely completion of the remaining trials and thus the generation of precise estimates for pandemic management before the development of vaccines.

Risk of COVID-19 infection and the associated hospitalization, ICU admission and mortality in opioid use disorder: a systematic review and meta-analysis

“…The adverse effects of opioids on the respiratory system and the associated increased histamine release caused by OUD also cause extubating challenges in these patients [ 30 – 32 , 46 , 47 ]. Moreover, medications used preliminary for COVID-19, such as hydroxychloroquine and azithromycin, although the efficacy could not be later established in studies [ 48 , 49 ], significantly interact with certain opioids, including methadone [ 50 , 51 ]. Clinicians should be, therefore, aware of the co-prescription of drugs and medicines used for opioid withdrawal in inpatients.…”

High-cited favorable studies for COVID-19 treatments ineffective in large trials

“…For treatments that do not have favorable results in large randomized trials, some evidence may provide support for consideration of a circumscribed use. For example, remdesivir recently showed promising results for an outpatient use in a randomized trial of 562 participants [67], convalescent plasma had favorable results in early outpatient intervention with high-titer dosing in a recent trial on 1,225 participants [68], and hydroxychloroquine has shown promising results for a preventive use with lower doses in a recent meta-analysis [69]. The best solution in these situations would be to consider whether there is room for conducting new large simple trials that focus on the debated settings, populations, and doses where there is continued controversy powering these trials to detect or reject the possibility of mortality benefits.…”

COVID‐19: Understanding the impact of anti‐hypertensive drugs and hydroxychloroquine on the ACE1 and ACE2 in lung and adipose tissue in SHR and WKY rats

“…However, other clinical studies showed no reduction in hospitalized patients (RECOVERY Collaborative Group et al, 2020 ) receiving HCQ treatment. A recent systematic study with meta‐analysis demonstrated that HCQ should not be ruled out for COVID‐19 treatment because results from clinical trials are still inconclusive for HCQ effectiveness (García‐Albéniz et al, 2022 ).…”