Hydroxychloroquine plus standard of care compared with standard of care alone in COVID-19: a meta-analysis of randomized controlled trials

  1. Bahman Amani
  2. Ahmad Khanijahani
  3. Behnam Amani

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Abstract

The efficacy and safety of Hydroxychloroquine (HCQ) in treating coronavirus disease (COVID-19) is disputed. This systematic review and meta-analysis aimed to examine the efficacy and safety of HCQ in addition to standard of care (SOC) in COVID-19. PubMed, the Cochrane Library, Embase, Web of sciences, and medRxiv were searched up to March 15, 2021. Clinical studies registry databases were also searched for identifying potential clinical trials. The references list of the key studies was reviewed to identify additional relevant resources. The quality of the included studies was evaluated using the Cochrane Collaboration tool and Jadad checklist. Meta-analysis was performed using RevMan software (version 5.3). Eleven randomized controlled trials with a total number of 8161 patients were identified as eligible for meta-analysis. No significant differences were observed between the two treatment groups in terms of negative rate of polymerase chain reaction (PCR) (Risk ratio [RR]: 0.99, 95% confidence interval (CI) 0.90, 1.08; P = 0.76), PCR negative conversion time (Mean difference [MD]: − 1.06, 95% CI − 3.10, 0.97; P = 0.30), all-cause mortality (RR: 1.09, 95% CI 1.00, 1.20; P = 0.06), body temperature recovery time (MD: − 0.64, 95% CI − 1.37, 0.10; P = 0.09), length of hospital stay (MD: − 0.17, 95% CI − 0.80, 0.46; P = 0.59), use of mechanical ventilation (RR: 1.12, 95% CI 0.95, 1.32; P = 0.19), and disease progression (RR = 0.82, 95% CI 0.37, 1.85; P = 0.64). However, there was a significant difference between two groups regarding adverse events (RR: 1.81, 95% CI 1.36, 2.42; P < 0.05). The findings suggest that the addition of HCQ to SOC has no benefit in the treatment of hospitalized patients with COVID-19. Additionally, it is associated with more adverse events.

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  1. Version published to 10.1038/s41598-021-91089-3
  2. ScreenIT

    SciScore for 10.1101/2020.06.05.20122705: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Institutional Review Board Statementnot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Search strategy: A systematic review of the relevant literature was conducted in PubMed, Cochrane Library, Embase and Google scholar up to June 1, 2020.
    PubMed
    suggested: (PubMed, RRID:SCR_004846)
    Cochrane Library
    suggested: (Cochrane Library, RRID:SCR_013000)
    Embase
    suggested: (EMBASE, RRID:SCR_001650)
    Google scholar
    suggested: (Google Scholar, RRID:SCR_008878)
    Other studies and reports such as letter to the editor, case reports, editorial comments, observational studies and animal models were excluded Data Extraction and Quality Assessment: Cochrane Collaboration’s tool was used to assess the risk of bias in the selected studies.
    Cochrane Collaboration’s
    suggested: None
    Both processes were independently performed by two authors, and disagreements were resolved by discussion among the authors Quantitative data synthesis: A meta-analysis was conducted to compare the efficacy and safety of HCQ versus standard treatment using RevMan (version 5.3) software.
    RevMan
    suggested: (RevMan, RRID:SCR_003581)

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    There are some concerns regarding the limitations of these studies which should be considered. All kinds of biases such as confounding, reverse causation, statistical considerations and other issues are the limitations of these studies in the estimation of drug efficacy and safety [29]. The Agency for Healthcare Research and Quality (AHRQ) has provided recommendations on including observational studies into the comparative effectiveness review process for comparing medical interventions [30]. Gautret et al [31] suggested that the causes of insufficient response to treatment with HCQ in the non-respondents with COVID-19 should be examined by factors such as SARS-CoV-2 strains, genome, and other factors associated with the metabolism of HCQ in patients. A possible mechanism for HCQ inefficiency was explained by Sandeep and McGregor [32] using virtualized quantum mechanical modeling. However, Yao et al [33] found that HCQ was more potent than Chloroquine inhabiting SARS-CoV-2 in vitro. Generally, the evidence for the efficacy and safety of HCQ is controversial. A meta-analysis by Shamshirian et al [28] confirms these findings and showed that HCQ treatment is associated with higher mortality (1.5 times). However, another Meta-analysis study showed that there was no significant difference between HCQ and control treatment for mortality [26]. Some studies supported the synergistic effect of HCQ with Azithromycin on COVID-19. A study [34] demonstrated the moderate in vitro effect of...

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  3. Version published to 10.1101/2020.06.05.20122705v1 on medRxiv