Pre-Exposure Prophylaxis with Various Doses of Hdroxychloroquine among high-risk COVID 19 Healthcare Personnel: CHEER randomized controlled trial

ImportanceRandomized clinical trials (RCTs) on COVID-19 are increasingly being posted as preprints before publication in a scientific, peer-reviewed journal.ObjectiveTo assess time to journal publication for COVID-19 RCT preprints and to compare differences between pairs of preprints and corresponding journal articles.Evidence ReviewThis systematic review used a meta-epidemiologic approach to conduct a literature search using the World Health Organization COVID-19 database and Embase to identify preprints published between January 1 and December 31, 2021. This review included RCTs with human participants and research questions regarding the treatment or prevention of COVID-19. For each preprint, a literature search was done to locate the corresponding journal article. Two independent reviewers read the full text, extracted data, and assessed risk of bias using the Cochrane Risk of Bias 2 tool. Time to publication was analyzed using a Cox proportional hazards regression model. Differences between preprint and journal article pairs in terms of outcomes, analyses, results, or conclusions were described. Statistical analysis was performed on October 17, 2022.FindingsThis study included 152 preprints. As of October 1, 2022, 119 of 152 preprints (78.3%) had been published in journals. The median time to publication was 186 days (range, 17-407 days). In a multivariable model, larger sample size and low risk of bias were associated with journal publication. With a sample size of less than 200 as the reference, sample sizes of 201 to 1000 and greater than 1000 had hazard ratios (HRs) of 1.23 (95% CI, 0.80-1.91) and 2.19 (95% CI, 1.36-3.53) for publication, respectively. With high risk of bias as the reference, medium-risk articles with some concerns for bias had an HR of 1.77 (95% CI, 1.02-3.09); those with a low risk of bias had an HR of 3.01 (95% CI, 1.71-5.30). Of the 119 published preprints, there were differences in terms of outcomes, analyses, results, or conclusions in 65 studies (54.6%). The main conclusion in the preprint contradicted the conclusion in the journal article for 2 studies (1.7%).Conclusions and RelevanceThese findings suggest that there is a substantial time lag from preprint posting to journal publication. Preprints with smaller sample sizes and high risk of bias were less likely to be published. Finally, although differences in terms of outcomes, analyses, results, or conclusions were observed for preprint and journal article pairs in most studies, the main conclusion remained consistent for the majority of studies.

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“…After abstract screening and full-text reading, 152 RCTs were included in the analysis. All 152 RCTs were posted on the medRxiv server …”

Section: Resultsmentioning

confidence: 99%

Comparison of Preprint Postings of Randomized Clinical Trials on COVID-19 and Corresponding Published Journal Articles

et al. 2023

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“…1 contains the PRISMA 2020 flow diagram). Eleven completed randomized trials were included in the metaanalysis: seven trials studied hydroxychloroquine as preexposure prophylaxis [19][20][21][22][23][24][25] and four as post-exposure prophylaxis [4,5,26,27].…”

Section: Resultsmentioning

confidence: 99%

“…The seven pre-exposure prophylaxis trials were doubleblinded, placebo-controlled trials that included healthcare workers with ongoing exposure to patients with COVID-19 [19][20][21][22][23][24][25]. The occurrence of COVID-19 was ascertained during a period between 4 and 12 weeks.…”

Section: Resultsmentioning

confidence: 99%

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

et al. 2022

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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.

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“…This article was previously posted to the medRxiv preprint server on May 17, 2021 [19]. deficiency, recent myocardial infarction (MI) and epileptic subjects were excluded.…”

Section: Introductionmentioning

confidence: 99%

Pre-exposure Prophylaxis With Various Doses of Hydroxychloroquine Among Healthcare Personnel With High-Risk Exposure to COVID-19: A Randomized Controlled Trial

Syed¹,

Hassan²,

Arif³

et al. 2021

Cureus

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This trial aimed to evaluate the safety and efficacy of pre-exposure prophylaxis (PrEP) with various hydroxychloroquine (HCQ) doses against a placebo among healthcare personnel (HCP) with high-risk exposure to coronavirus disease 2019 (COVID 19). MethodsA phase II, randomized, placebo-controlled trial was conducted including 200 subjects with no active or past severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (antibody testing and reverse transcription-polymerase chain reaction (RT-PCR) were taken at the time of enrollment). Subjects of experimental groups one to three received HCQ in various doses and the control group received a placebo. The study outcomes in terms of safety and efficacy were monitored. Participants exhibiting COVID-19 symptoms were tested for SARS-CoV-2 during the study and by the end of week 12 with RT-PCR or serology testing (COVID-19 IgM/IgG antibody testing). ResultsOut of the total participants, 146 reported exposure to a confirmed COVID-19 case in the first month, and 192 were exposed by week 12 of the study. Moreover, the precautionary use of personal protective equipment (PPE) significantly varied; initially more than 80% of the exposed HCPs were not ensuring PPE being used by the patients treated by them, which gradually developed over time. Mild treatment-related side effects were observed among the interventional and placebo arm patients. There was no significant clinical benefit of PrEP with HCQ as compared to placebo (p>0.05). ConclusionIt is concluded that the PrEP HCQ does not significantly prevent COVID-19 among high-risk HCPs.

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Pre-Exposure Prophylaxis with Various Doses of Hdroxychloroquine among high-risk COVID 19 Healthcare Personnel: CHEER randomized controlled trial

Cited by 6 publications

References 20 publications

Comparison of Preprint Postings of Randomized Clinical Trials on COVID-19 and Corresponding Published Journal Articles

Comparison of Preprint Postings of Randomized Clinical Trials on COVID-19 and Corresponding Published Journal Articles

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

Pre-exposure Prophylaxis With Various Doses of Hydroxychloroquine Among Healthcare Personnel With High-Risk Exposure to COVID-19: A Randomized Controlled Trial

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