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Old drugs for a new indication: a review of chloroquine and analogue in COVID-19 treatment.

ABSTRACT: As an innovative therapeutic strategy, drug repurposing affords old, approved, and already established drugs a chance at new indications. In the wake of the COVID-19 pandemic and the accompanied urgency for a lasting treatment, drug repurposing has come in handy to stem the debilitating effects of the disease. Among other therapeutic options currently in clinical trials, chloroquine (CQ) and the hydroxylated analogue, hydroxychloroquine (HCQ) have been frontline therapeutic options in most formal and informal clinical settings with varying degrees of efficacy against this life-threatening disease. Their status in randomized clinical trials is related to the biochemical and pharmacological profiles as validated by in vitro, in vivo and case studies. With the aim to bear a balance for their use in the long run, this review not only synopsizes findings from recent studies on the degrees of efficacy and roles of CQ/HCQ as potential anti-COVID-19 agents but also highlights our perspectives for their consideration in rational drug repositioning and use.

SUBMITTER: Ehianeta TS

PROVIDER: S-EPMC8202634 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Background: Anti-malarial drugs inhibit coronaviruses in-vitro. Few published studies have evaluated the safety and efficacy of these drugs in the treatment of COVID-19 infection. Materials and Methods: This is a systematic review and meta-analysis of clinical trials and observational studies. Major database searches were carried out up until June 5, 2020. Participants admitted with RT-PCR-confirmed SARS Cov-2 (COVID-19) infection were included. The "Intervention group" received anti-malarial drugs with or without other drugs (Azithromycin) administered as an adjunct to the standard treatment/care. The "Control group" received treatment except anti-malarial drugs. The primary outcome is "all-cause mortality." Secondary outcome measures were effects on clinical and laboratory parameters and adverse events. Results: Of 3,472 citations, 17 (six clinical trials and 11 observational studies) studies provided data of 8,071 participants. Compared to the control, Hydroxy-chloroquine (HCQ) has no significant effect on mortality [(OR 0.87; 95% CI 0.46-1.64); eight observational studies; N = 5,944]. Data from a single, small non-randomized trial (N = 42) also reached a similar conclusion (OR 1.94; 95% CI 0.07-50.57; p = 0.69). Compared to the control, HCQ plus Azithromycin (AZM) significantly increased mortality [(OR 2.84; 95% CI 2.19-3.69); four observational studies; N = 2,310]. Compared to the control, risk of any adverse event was significantly increased in HCQ group [(OR 3.35; 95% CI 1.58-7.13); four clinical trials; N = 263]. Compared to control, risk of adverse cardiac events (abnormal ECG, arrhythmia, or QT prolongation) were not significantly increased in HCQ group (but significantly increased in the HCQ plus AZM group). The GRADE evidence generated for all the outcomes was of "very low-quality." Conclusions: As very low quality evidence suggests an increased risk of mortality and adverse event with HCQ plus Azithromycin combination (not HCQ alone), caution should be exercised while prescribing this combination for treatment of hospitalized adults with COVID-19 infection. Good quality, multi-centric RCTs (including both hospitalized and non-hospitalized patients) are required for any firm recommendation to be made during the ongoing pandemic. OSF Protocol Registration Link: https://osf.io/6zxsu.

Project description:IntroductionGiven the current lack of an approved and effective treatment or vaccine for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), repositioning old drugs for use as an antiviral treatment is an interesting strategy because knowledge about these drugs' safety profile, posology, and drug interactions is already known. Chloroquine and hydroxychloroquine, widely used as antimalarial and autoimmune disease drugs, have recently been reported as a potential broad-spectrum antiviral drug.BackgroundThe in vitro antiviral activity of chloroquine has been identified since the late 1960s. However, antiviral mechanisms of chloroquine remain speculative. Several clinical trials have been conducted to test the efficacy and safety of chloroquine or hydroxychloroquine in the treatment of COVID-19-associated pneumonia. The quality of the studies and the outcomes are evaluated in this systematic review and meta-analysis.Review resultsLiterature review revealed 23 clinical studies. Only 9 of 23 studies were randomized controlled trials. Of nine randomized controlled trials, only study by Skipper et al. was deemed to be at low risk of bias. All studies evaluated variedwith different outcomes. Mechanical ventilation and virological clearance were the only common outcomes evaluated in more than two studies. Virological clearance odds ratio (OR) was 1.25 (95% confidence interval [CI] of 0.57-2.73; Chi2 = 0.83; I2 = 0%). GRADE quality of evidence was downgraded by three levels to very low due to concerns about the risk of bias, inconsistency, and imprecision. For mechanical ventilation, OR was 1.09 (95% CI 0.80-1.50; Chi2 = 0; I2 = 0). GRADE quality of evidence was downgraded by two levels to low due to concerns about the risk of bias and imprecision. There was no statistically significant difference between the groups for these two outcomes.ConclusionAs per the available evidence, based on our review, we conclude that hydroxychloroquine/chloroquine has not shown to be beneficial when used for the treatment of patients with COVID-19 pneumonia.How to cite this articleShetty RM, Namachivayam A. Evidence for Chloroquine/Hydroxychloroquine in the Treatment of COVID-19. Indian J Crit Care Med 2021;25(4):441-452.

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Old drugs for a new indication: a review of chloroquine and analogue in COVID-19 treatment.

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