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Comparative Effectiveness of Pharmacological Interventions for Covid-19: A Systematic Review and Network Meta-Analysis.
De Crescenzo, Franco; Amato, Laura; Cruciani, Fabio; Moynihan, Luke P; D'Alò, Gian Loreto; Vecchi, Simona; Saulle, Rosella; Mitrova, Zuzana; Di Franco, Valeria; Addis, Antonio; Davoli, Marina.
  • De Crescenzo F; Department of Psychiatry, University of Oxford, Oxford, United Kingdom.
  • Amato L; Department of Epidemiology of the Regional Health Service Lazio, Rome, Italy.
  • Cruciani F; Paediatric University Hospital-Department (DPUO), Bambino Gesù Children's Hospital, Rome, Italy.
  • Moynihan LP; Department of Epidemiology of the Regional Health Service Lazio, Rome, Italy.
  • D'Alò GL; Department of Epidemiology of the Regional Health Service Lazio, Rome, Italy.
  • Vecchi S; Department of Acute Medicine, University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom.
  • Saulle R; Department of Epidemiology of the Regional Health Service Lazio, Rome, Italy.
  • Mitrova Z; Department of Epidemiology of the Regional Health Service Lazio, Rome, Italy.
  • Di Franco V; Department of Epidemiology of the Regional Health Service Lazio, Rome, Italy.
  • Addis A; Department of Epidemiology of the Regional Health Service Lazio, Rome, Italy.
  • Davoli M; Department of Anaesthesiology and Intensive Care Medicine, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.
Front Pharmacol ; 12: 649472, 2021.
Article in English | MEDLINE | ID: covidwho-1236739
ABSTRACT

Background:

Several pharmacological interventions are now under investigation for the treatment of Covid-19, and the evidence is evolving rapidly. Our aim is to assess the comparative efficacy and safety of these drugs. Methods and

Findings:

We performed a systematic review and network meta-analysis searching Medline, Pubmed, Embase, Cochrane Covid-19 register, international trial registers, medRxiv, bioRxiv, and arXiv up to December 10, 2020. We included all randomised controlled trials (RCTs) comparing any pharmacological intervention for Covid-19 against any drugs, placebo or standard care (SC). Data extracted from published reports were assessed for risk of bias in accordance with the Cochrane tool, and using the GRADE framework. Primary outcomes were all-cause mortality, adverse events (AEs) and serious adverse events (SAEs). We estimated summary risk ratio (RR) using pairwise and network meta-analysis with random effects (Prospero, number CRD42020176914). We performed a systematic review and network meta-analysis searching Medline, Pubmed, Embase, Cochrane Covid-19 register, international trial registers, medRxiv, bioRxiv, and arXiv up to December 10, 2020. We included all randomised controlled trials (RCTs) comparing any pharmacological intervention for Covid-19 against any drugs, placebo or standard care (SC). Data extracted from published reports were assessed for risk of bias in accordance with the Cochrane tool, and using the GRADE framework. Primary outcomes were all-cause mortality, adverse events (AEs) and serious adverse events (SAEs). We estimated summary risk ratio (RR) using pairwise and network meta-analysis with random effects (Prospero, number CRD42020176914). We included 96 RCTs, comprising of 34,501 patients. The network meta-analysis showed in terms of all-cause mortality, when compared to SC or placebo, only corticosteroids significantly reduced the mortality rate (RR 0.90, 95%CI 0.83, 0.97; moderate certainty of evidence). Corticosteroids significantly reduced the mortality rate also when compared to hydroxychloroquine (RR 0.83, 95%CI 0.74, 0.94; moderate certainty of evidence). Remdesivir proved to be better in terms of SAEs when compared to SC or placebo (RR 0.75, 95%CI 0.63, 0.89; high certainty of evidence) and plasma (RR 0.57, 95%CI 0.34, 0.94; high certainty of evidence). The combination of lopinavir and ritonavir proved to reduce SAEs when compared to plasma (RR 0.49, 95%CI 0.25, 0.95; high certainty of evidence). Most of the RCTs were at unclear risk of bias (42 of 96), one third were at high risk of bias (34 of 96) and 20 were at low risk of bias. Certainty of evidence ranged from high to very low.

Conclusion:

At present, corticosteroids reduced all-cause mortality in patients with Covid-19, with a moderate certainty of evidence. Remdesivir appeared to be a safer option than SC or placebo, while plasma was associated with safety concerns. These preliminary evidence-based observations should guide clinical practice until more data are made public.
Keywords

Full text: Available Collection: International databases Database: MEDLINE Type of study: Experimental Studies / Observational study / Prognostic study / Randomized controlled trials / Reviews / Systematic review/Meta Analysis Language: English Journal: Front Pharmacol Year: 2021 Document Type: Article Affiliation country: Fphar.2021.649472

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Full text: Available Collection: International databases Database: MEDLINE Type of study: Experimental Studies / Observational study / Prognostic study / Randomized controlled trials / Reviews / Systematic review/Meta Analysis Language: English Journal: Front Pharmacol Year: 2021 Document Type: Article Affiliation country: Fphar.2021.649472