Open-label randomized control trial of hydroxychloroquine in patients with moderate to severe coronavirus disease 2019 infection

Gupta, Salil; Dixit, Pradipkumar; Ghana, Parthasarathi; Abhisheka, Kumar; Khurana, Harshit; Jha, Vijoy Kumar; Mahapatra, Debasish; Goel, Jitesh; Ahmed, Safia K.; Varadaraj, G

doi:10.1016/j.mjafi.2021.02.007

Cited by 4 publications

(2 citation statements)

References 18 publications

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“…Overall, 115 studies with 77,128 patients reported the number of patients requiring mechanical ventilation during the study period. We included ACEIs/ARBs, ammonium chloride, azithromycin, bamlanivimab, baricitinib plus remdesivir, bromhexine, budesonide, camostat mesilate, canakinumab, chloroquine, colchicine, convalescent plasma, dexamethasone, doxycycline, favipiravir, hydroxychloroquine, hydroxychloroquine plus azithromycin, hydroxychloroquine plus favipiravir, imatinib, INM005, interferon beta, intravenous immunoglobulin, ivermectin, lopinavir/ritonavir, methylprednisolone, recombinant human GCSF, remdesivir, sarilumab, sofosbuvir plus daclatasvir, sulodexide, tocilizumab, tofacitinib, vitamin D3 and SOC as treatment nodes in the NMA, for which observations came from 84 studies ( 3 , 6 , 22 – 26 , 28 – 31 , 35 , 42 , 43 , 46 , 47 , 50 , 53 , 55 , 57 – 61 , 63 , 64 , 66 , 67 , 71 , 73 – 77 , 79 , 80 , 82 , 83 , 85 – 87 , 89 , 92 – 94 , 96 – 100 , 102 , 105 – 107 , 109 , 111 – 118 , 120 – 124 , 126 , 128 – 132 , 134 , 135 , 139 , 140 , 145 , 151 , 152 , 154 – 156 ). About one-third (26/84) of the included studies were evaluated as low risk ( Supplementary Table 6 ).…”

Section: Resultsmentioning

confidence: 99%

Efficacy of COVID-19 Treatments: A Bayesian Network Meta-Analysis of Randomized Controlled Trials

Zhang

Jin

Wen

et al. 2021

Front. Public Health

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Background: We provided a comprehensive evaluation of efficacy of available treatments for coronavirus disease 2019 (COVID-19).Methods: We searched for candidate COVID-19 studies in WHO COVID-19 Global Research Database up to August 19, 2021. Randomized controlled trials for suspected or confirmed COVID-19 patients published on peer-reviewed journals were included, regardless of demographic characteristics. Outcome measures included mortality, mechanical ventilation, hospital discharge and viral clearance. Bayesian network meta-analysis with fixed effects was conducted to estimate the effect sizes using posterior means and 95% equal-tailed credible intervals (CrIs). Odds ratio (OR) was used as the summary measure for treatment effect. Bayesian hierarchical models were used to estimate effect sizes of treatments grouped by the treatment classifications.Results: We identified 222 eligible studies with a total of 102,950 patients. Compared with the standard of care, imatinib, intravenous immunoglobulin and tocilizumab led to lower risk of death; baricitinib plus remdesivir, colchicine, dexamethasone, recombinant human granulocyte colony stimulating factor and tocilizumab indicated lower occurrence of mechanical ventilation; tofacitinib, sarilumab, remdesivir, tocilizumab and baricitinib plus remdesivir increased the hospital discharge rate; convalescent plasma, ivermectin, ivermectin plus doxycycline, hydroxychloroquine, nitazoxanide and proxalutamide resulted in better viral clearance. From the treatment class level, we found that the use of antineoplastic agents was associated with fewer mortality cases, immunostimulants could reduce the risk of mechanical ventilation and immunosuppressants led to higher discharge rates.Conclusions: This network meta-analysis identified superiority of several COVID-19 treatments over the standard of care in terms of mortality, mechanical ventilation, hospital discharge and viral clearance. Tocilizumab showed its superiority compared with SOC on preventing severe outcomes such as death and mechanical ventilation as well as increasing the discharge rate, which might be an appropriate treatment for patients with severe or mild/moderate illness. We also found the clinical efficacy of antineoplastic agents, immunostimulants and immunosuppressants with respect to the endpoints of mortality, mechanical ventilation and discharge, which provides valuable information for the discovery of potential COVID-19 treatments.

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Section: Resultsmentioning

confidence: 99%

Efficacy of COVID-19 Treatments: A Bayesian Network Meta-Analysis of Randomized Controlled Trials

Zhang

Jin

Wen

et al. 2021

Front. Public Health

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“… 43 Additionally, combined with azithromycin, it was not associated with decreased mortality in patients hospitalized for mild and moderate COVID-19; 44 , 45 furthermore, it did not change the number of days of hospitalization to discharge or death. 46 …”

Section: Antiparasiticmentioning

confidence: 99%

Effectiveness of Drug Repurposing and Natural Products Against SARS-CoV-2: A Comprehensive Review

Velásquez,

Hernandez,

Galeano

et al. 2024

CPAA

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The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a betacoronavirus responsible for the COVID-19 pandemic, causing respiratory disorders, and even death in some individuals, if not appropriately treated in time. To face the pandemic, preventive measures have been taken against contagions and the application of vaccines to prevent severe disease and death cases. For the COVID-19 treatment, antiviral, antiparasitic, anticoagulant and other drugs have been reused due to limited specific medicaments for the disease. Drug repurposing is an emerging strategy with therapies that have already tested safe in humans. One promising alternative for systematic experimental screening of a vast pool of compounds is computational drug repurposing (in silico assay). Using these tools, new uses for approved drugs such as chloroquine, hydroxychloroquine, ivermectin, zidovudine, ribavirin, lamivudine, remdesivir, lopinavir and tenofovir/emtricitabine have been conducted, showing effectiveness in vitro and in silico against SARS-CoV-2 and some of these, also in clinical trials. Additionally, therapeutic options have been sought in natural products (terpenoids, alkaloids, saponins and phenolics) with promising in vitro and in silico results for use in COVID-19 disease. Among these, the most studied are resveratrol, quercetin, hesperidin, curcumin, myricetin and betulinic acid, which were proposed as SARS-CoV-2 inhibitors. Among the drugs reused to control the SARS-CoV2, better results have been observed for remdesivir in hospitalized patients and outpatients. Regarding natural products, resveratrol, curcumin, and quercetin have demonstrated in vitro antiviral activity against SARS-CoV-2 and in vivo, a nebulized formulation has demonstrated to alleviate the respiratory symptoms of COVID-19. This review shows the evidence of drug repurposing efficacy and the potential use of natural products as a treatment for COVID-19. For this, a search was carried out in PubMed, SciELO and ScienceDirect databases for articles about drugs approved or under study and natural compounds recognized for their antiviral activity against SARS-CoV-2.

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Pooled evidence precision of clinical trials on hydroxychloroquine for Covid-19 treatment was stabilized eight months after the outbreak

Ribeiro,

Ramirez,

Melo

et al. 2024

Preprint

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OBJECTIVE At the beginning of 2020, hydroxychloroquine showed promising in vitro activity for Covid-19 and several studies were oriented to assess its safety and efficacy. However, after a few months, hydroxychloroquine has proved ineffective. The randomized controlled trials (RCTs) developed quickly and in different settings represent the scientific community capacity to assess drug repositioning effectiveness during a sanitary crisis. Therefore, a critical evaluation of the evidence generated can guide future efforts in analogous situations. We aimed to analyze the RCTs assessing the efficacy of hydroxychloroquine in treating Covid-19, describe their internal validity and power, and evaluate their contribution to the precision of the combined evidence for assessing the mortality outcome. STUDY DESIGN AND SETTINGS This meta-research included RCTs assessing hydroxychloroquine to treat patients diagnosed with Covid-19. It was part of an umbrella systematic review of methods/meta-research (PROSPERO: CRD42022360331) that included a comprehensive search in MEDLINE, EMBASE, Cochrane Library, and the Latin America Database - Lilacs. We retrieved studies published until January 10th, 2022. The risk of bias was assessed using Cochrane Risk of Bias (RoB) 2.0. We analyzed methodology of the studies, precision and random error change through time from pooled evidence, study comparators, patient important outcome, power in different magnitude of effects proxy. RESULTS A total of 22 RCT were included, from that 17 (77%) assessed hospitalized patients and five (23%) outpatients setting. Mortality was related as primary endpoint in only four studies, however half of the studies included composite endpoints including mortality as a component. The internal validity analysis using RoB2 found that eight studies (36%) had a high risk of bias. Only one study had sufficient power to evaluate a moderate magnitude of effect (RR = 0,7 on mortality). The standard error to evaluate efficacy on mortality did not change appreciably after October 2020. From Oct 2020 to Dec 2021, 18 additional studies were published with 2,429 patients recruited. CONCLUSION This meta-research highlights the impact that collaborative, and network scientific research have on informing clinical decision-making. Duplicate efforts create research waste as precision analysis shows that after October 2020, there was not appreciably changes in the precision of the pooled RCT evidence to estimate the hydroxychloroquine effect on mortality.

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Open-label randomized control trial of hydroxychloroquine in patients with moderate to severe coronavirus disease 2019 infection

Cited by 4 publications

References 18 publications

Efficacy of COVID-19 Treatments: A Bayesian Network Meta-Analysis of Randomized Controlled Trials

Efficacy of COVID-19 Treatments: A Bayesian Network Meta-Analysis of Randomized Controlled Trials

Effectiveness of Drug Repurposing and Natural Products Against SARS-CoV-2: A Comprehensive Review

Pooled evidence precision of clinical trials on hydroxychloroquine for Covid-19 treatment was stabilized eight months after the outbreak

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