Evaluation of oral small molecule drugs for the treatment of COVID-19 patients: a systematic review and network meta-analysis.
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ABSTRACT: Introduction
At present, there are some randomized controlled trials (RCTs) of oral small molecule drugs. The purpose of this study was to evaluate the efficacy and safety of oral small molecule drug treatment for COVID-19.Methods
RCTs were identified through systematic searches of PubMed, Embase, and Cochrane Central Register of Controlled Trials through 1 April 2023. A total of nine RCTs were included, including 30,970 COVID-19 patients comparing five treatments (azvudine, molnupiravir, paxlovid, VV116, and placebo). The Cochrane risk of bias tool for randomized trials (RoB) was used to assess the bias risk of the included studies. The direct and indirect evidence were combined using a Bayesian network meta-analysis (PROSPERO Code No: CRD42023397837).Results
Direct analysis showed that paxlovid was associated with a reduced risk of mortality (odds ratio [OR] 0.12, 95% confidence interval [CI] 0.06-0.25) and hospitalization (OR = 0.04, 95% CI: 0.00-0.67) compared with placebo. Network meta-analysis showed that paxlovid had the highest probability of being the best management strategy in patients with COVID-19, reducing mortality (OR = 0.11, 95% CI: 0.01-1.99; surface under the cumulative ranking curve [SUCRA]: 0.77) and hospitalization (OR = 0.06, 95% CI: 0.00-1.03; SUCRA: 0.95). For prespecified safety outcomes, SUCRA values ranked VV116 (OR = 0.09, 95% CI: 0.00-2.07: SUCRA 0.86) as the most beneficial intervention for the prevention of serious adverse events.Conclusions
When compared to other antiviral medications, paxlovid can reduce the mortality and hospitalization of COVID-19 patients.
SUBMITTER: Chen Z
PROVIDER: S-EPMC10768866 | biostudies-literature | 2023
REPOSITORIES: biostudies-literature
Publications
Evaluation of oral small molecule drugs for the treatment of COVID-19 patients: a systematic review and network meta-analysis.
Chen Zhaoyan Z Tian Fangyuan F
Annals of medicine 20231115 2
<h4>Introduction</h4>At present, there are some randomized controlled trials (RCTs) of oral small molecule drugs. The purpose of this study was to evaluate the efficacy and safety of oral small molecule drug treatment for COVID-19.<h4>Methods</h4>RCTs were identified through systematic searches of PubMed, Embase, and Cochrane Central Register of Controlled Trials through 1 April 2023. A total of nine RCTs were included, including 30,970 COVID-19 patients comparing five treatments (azvudine, moln ...[more]
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Project description:UpdatesThis is the second version (first update) of the living systematic review, replacing the previous version (available as a data supplement). When citing this paper please consider adding the version number and date of access for clarity.ObjectiveTo determine and compare the effects of drug prophylaxis on severe acute respiratory syndrome coronavirus virus 2 (SARS-CoV-2) infection and coronavirus disease 2019 (covid-19).DesignLiving systematic review and network meta-analysis (NMA).Data sourcesWorld Health Organization covid-19 database, a comprehensive multilingual source of global covid-19 literature to 4 March 2022.Study selectionRandomised trials in which people at risk of covid-19 were allocated to prophylaxis or no prophylaxis (standard care or placebo). Pairs of reviewers independently screened potentially eligible articles.MethodsAfter duplicate data abstraction, we conducted random-effects bayesian network meta-analysis. We assessed risk of bias of the included studies using a modification of the Cochrane risk of bias 2.0 tool and assessed the certainty of the evidence using the grading of recommendations assessment, development and evaluation (GRADE) approach.ResultsThe second iteration of this living NMA includes 32 randomised trials which enrolled 25 147 participants and addressed 21 different prophylactic drugs; adding 21 trials (66%), 18 162 participants (75%) and 16 (76%) prophylactic drugs. Of the 16 prophylactic drugs analysed, none provided convincing evidence of a reduction in the risk of laboratory confirmed SARS-CoV-2 infection. For admission to hospital and mortality outcomes, no prophylactic drug proved different than standard care or placebo. Hydroxychloroquine and vitamin C combined with zinc probably increase the risk of adverse effects leading to drug discontinuation—risk difference for hydroxychloroquine (RD) 6 more per 1000 (95% credible interval (CrI) 2 more to 10 more); for vitamin C combined with zinc, RD 69 more per 1000 (47 more to 90 more), moderate certainty evidence.ConclusionsMuch of the evidence remains very low certainty and we therefore anticipate future studies evaluating drugs for prophylaxis may change the results for SARS-CoV-2 infection, admission to hospital and mortality outcomes. Both hydroxychloroquine and vitamin C combined with zinc probably increase adverse effects.Systematic review registrationThis review was not registered. The protocol established a priori is included as a supplement.FundingThis study was supported by the Canadian Institutes of Health Research (grant CIHR-IRSC:0579001321).
| S-EPMC8073806 | biostudies-literature
Project description:AimsThe aim of this study was to continually evaluate the association between cardiovascular drug exposure and COVID-19 clinical outcomes (susceptibility to infection, disease severity, hospitalization, hospitalization length, and all-cause mortality) in patients at risk of/with confirmed COVID-19.MethodsEligible publications were identified from more than 500 databases on 1 November 2020. One reviewer extracted data with 20% of the records independently extracted/evaluated by a second reviewer.ResultsOf 52 735 screened records, 429 and 390 studies were included in the qualitative and quantitative syntheses, respectively. The most-reported drugs were angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs) with ACEI/ARB exposure having borderline association with confirmed COVID-19 infection (OR 1.14, 95% CI 1.00-1.31). Among COVID-19 patients, unadjusted estimates showed that ACEI/ARB exposure was associated with hospitalization (OR 1.76, 95% CI 1.34-2.32), disease severity (OR 1.40, 95% CI 1.26-1.55) and all-cause mortality (OR 1.22, 95% CI 1.12-1.33) but not hospitalization length (mean difference -0.27, 95% CI -1.36-0.82 days). After adjustment, ACEI/ARB exposure was not associated with confirmed COVID-19 infection (OR 0.92, 95% CI 0.71-1.19), hospitalization (OR 0.93, 95% CI 0.70-1.24), disease severity (OR 1.05, 95% CI 0.81-1.38) or all-cause mortality (OR 0.84, 95% CI 0.70-1.00). Similarly, subgroup analyses involving only hypertensive patients revealed that ACEI/ARB exposure was not associated with confirmed COVID-19 infection (OR 0.93, 95% CI 0.79-1.09), hospitalization (OR 0.84, 95% CI 0.58-1.22), hospitalization length (mean difference -0.14, 95% CI -1.65-1.36 days), disease severity (OR 0.92, 95% CI 0.76-1.11) while it decreased the odds of dying (OR 0.76, 95% CI 0.65-0.88). A similar trend was observed for other cardiovascular drugs. However, the validity of these findings is limited by a high level of heterogeneity and serious risk of bias.ConclusionCardiovascular drugs are not associated with poor COVID-19 outcomes in adjusted analyses. Patients should continue taking these drugs as prescribed.
| S-EPMC8239929 | biostudies-literature
Project description:BackgroundSevere acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is responsible for the outbreak of COVID-19 in Wuhan, China. As a highly infectious epidemic, SARS-CoV-2 rapidly evolves. Presently, COVID-19 coexists with humans, mainly with mild or moderate disease. The latest Guidelines for the Diagnosis and Treatment of COVID-19 (trial version of the 10th Edition) recommend several oral traditional Chinese medicines (TCMs) for treatment. This study aims to evaluate the evidence-based benefits of these TCMs as adjunctive therapies to conventional western medicine (CWM) for patients with mild or moderate COVID-19.MethodsWe conducted a systematic review and meta-analysis adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, utilizing the PRISMA checklist. We searched PubMed, Cochrane Library, Embase, CNKI, and Wan-Fang databases to retrieve randomized controlled trials and retrospective cohort studies of TCM in combination with CWM on the treatment of mild or moderate COVID-19 that were published as of December 25, 2023. A network meta-analysis using the frequency model was employed to evaluate the benefits of different interventions.ResultsA total of 30 eligible studies, enrolling 4144 participants, utilized 7 marketed oral TCMs in China. Compared with CWM alone, the integration of TCMs with CWM can significantly reduce severe conversion rate. This combined approach also enhances the clinical effective rate, shortens the negative conversion time of nucleic acid, and improves both symptoms and blood biochemical markers in patients. The network meta-analysis provided preliminary evidence of the superiority of specific TCMs for various outcomes: Qingfei Paidu for raising the CT improvement rate and clinical effective rate, and shortening the negative conversion time of nucleic acid; Huashi Baidu for reducing severe conversion and improving cough; Xuanfei Baidu for improving fatigue; Jinhua Qinggan for improving fever; Lianhua Qingwen for shortening the recovery time of fatigue and cough; and Shufeng Jiedu for shortening the recovery time of fever.ConclusionsTCM in combination with CWM may be beneficial for patients with mild or moderate COVID-19. Each TCM may have distinct benefits in COVID-19.
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Project description:ObjectiveTo compare the effects of treatments for coronavirus disease 2019 (covid-19).DesignLiving systematic review and network meta-analysis.Data sourcesWHO covid-19 database, a comprehensive multilingual source of global covid-19 literature, up to 3 December 2021 and six additional Chinese databases up to 20 February 2021. Studies identified as of 1 December 2021 were included in the analysis.Study selectionRandomised clinical trials in which people with suspected, probable, or confirmed covid-19 were randomised to drug treatment or to standard care or placebo. Pairs of reviewers independently screened potentially eligible articles.MethodsAfter duplicate data abstraction, a bayesian network meta-analysis was conducted. Risk of bias of the included studies was assessed using a modification of the Cochrane risk of bias 2.0 tool, and the certainty of the evidence using the grading of recommendations assessment, development, and evaluation (GRADE) approach. For each outcome, interventions were classified in groups from the most to the least beneficial or harmful following GRADE guidance.Results463 trials enrolling 166 581 patients were included; 267 (57.7%) trials and 89 814 (53.9%) patients are new from the previous iteration; 265 (57.2%) trials evaluating treatments with at least 100 patients or 20 events met the threshold for inclusion in the analyses. Compared with standard care, three drugs reduced mortality in patients with mostly severe disease with at least moderate certainty: systemic corticosteroids (risk difference 23 fewer per 1000 patients, 95% credible interval 40 fewer to 7 fewer, moderate certainty), interleukin-6 receptor antagonists when given with corticosteroids (23 fewer per 1000, 36 fewer to 7 fewer, moderate certainty), and Janus kinase inhibitors (44 fewer per 1000, 64 fewer to 20 fewer, high certainty). Compared with standard care, two drugs probably reduce hospital admission in patients with non-severe disease: nirmatrelvir/ritonavir (36 fewer per 1000, 41 fewer to 26 fewer, moderate certainty) and molnupiravir (19 fewer per 1000, 29 fewer to 5 fewer, moderate certainty). Remdesivir may reduce hospital admission (29 fewer per 1000, 40 fewer to 6 fewer, low certainty). Only molnupiravir had at least moderate quality evidence of a reduction in time to symptom resolution (3.3 days fewer, 4.8 fewer to 1.6 fewer, moderate certainty); several others showed a possible benefit. Several drugs may increase the risk of adverse effects leading to drug discontinuation; hydroxychloroquine probably increases the risk of mechanical ventilation (moderate certainty).ConclusionCorticosteroids, interleukin-6 receptor antagonists, and Janus kinase inhibitors probably reduce mortality and confer other important benefits in patients with severe covid-19. Molnupiravir and nirmatrelvir/ritonavir probably reduce admission to hospital in patients with non-severe covid-19.Systematic review registrationThis review was not registered. The protocol is publicly available in the supplementary material.Readers' noteThis article is a living systematic review that will be updated to reflect emerging evidence. Updates may occur for up to two years from the date of original publication. This is the fifth version of the original article published on 30 July 2020 (BMJ 2020;370:m2980), and previous versions can be found as data supplements. When citing this paper please consider adding the version number and date of access for clarity.
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