Azithromycin in Hospitalised Patients with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Horby, Peter; Roddick, Alistair; Spata, Enti; Staplin, Natalie; Emberson, Jonathan; Pessoa-Amorim, Guilherme; Peto, Leon; Campbell, Mark; Brightling, Christopher; Prudon, Ben; Chadwick, David; Ustianowski, Andrew; Ashish, Abdul; Todd, Stacy; Yates, Bryan; Buttery, Robert; Scott, Stephen; Maseda, Diego; Baillie, J Kenneth; Buch, Maya H; Chappell, Lucy C; Day, Jeremy; Faust, Saul N; Jaki, Thomas; Jeffery, Katie; Juszczak, Ed; Lim, Wei Shen; Montgomery, Alan; Mumford, Andrew D; Rowan, Kathryn M; Thwaites, Guy; Mafham, Marion; Haynes, Richard; Landray, Martin J

doi:10.1101/2020.12.10.20245944

Cited by 18 publications

(24 citation statements)

References 25 publications

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“…Out of these, 146 studies were further reviewed for full text and 96 eligible studies reporting 93 unique randomized clinical trials were included in the systematic review, 2, 5, 15-18, 36-125 where the RECOVERY trial was reported in four studies. 2, 15, 16, 76 Figure 1 summarizes the process of our study selection.…”

Section: Resultsmentioning

confidence: 99%

“…Among the 96 studies, ten were multi-arm and the rest were two-arm; 69 studies compared the investigated intervention with SOC, 19 with other active comparators and the other eight with both SOC and other interventions. About half of the studies (47/96) were of small sample size which enrolled less than 100 patients in the intention-to-treat population, seven studies recruited over 1000 patients, including four reports for the RECOVERY trial 2, 15, 16, 76 , one for the SOLIDARITY 17 trial, one for remdesivir 5 and one for baricitinib plus remdesivir 83 . Of 74 studies which recorded the baseline severity of illness, 28 involved patients mainly with severe or critical COVID-19 and 46 were mainly for mild/moderate disease.…”

Section: Resultsmentioning

confidence: 99%

“…A total of 74 studies 2, 5, 15-18, 36-39, 41-44, 47-54, 56, 57, 59-63, 65-67, 69, 70, 72, 74-76, 78, 79, 82, 83, 85, 87, 88, 90-92, 94-97, 99, 100, 103-121, 125 including 48622 patients reported all-cause mortality. After filtering out treatments with small sample size following the specified criteria, the network included azithromycin, hydroxychloroquine, hydroxychloroquine plus azithromycin, colchicine, arbidol (umifenovir), favipiravir, remdesivir, lopinavir/ritonavir, convalescent plasma, methylprednisolone, dexamethasone, hydrocortisone, immunoglobulin, interferon beta, recombinant human granulocyte colony-stimulating factor (GCSF), tocilizumab, vitamin D 3 , baricitinib plus remdesivir, sulodexide and SOC.…”

Section: Resultsmentioning

confidence: 99%

“…Overall, 48 studies reported the number of patients required for MV during the study period. 2, 5, 15-17, 36-39, 41-44, 47-50, 56, 57, 60-63, 65, 69, 72, 76, 78, 82, 83, 87, 92, 95-97, 100, 103-105, 108-110, 112-114, 116, 117, 120 with 41405 patients and 4455 events. We included azithromycin, hydroxychloroquine, hydroxychloroquine plus azithromycin, remdesivir, lopinavir/ritonavir, convalescent plasma, methylprednisolone, dexamethasone, hydrocortisone, immunoglobulin, interferon beta, recombinant human GCSF, tocilizumab, vitamin D 3 , baricitinib plus remdesivir, sulodexide and SOC as treatment nodes in the NMA.…”

Section: Resultsmentioning

confidence: 99%

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A Systematic Review and Network Meta-Analysis for COVID-19 Treatments

Zhang

Jin

Wen

et al. 2020

Preprint

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BackgroundNumerous interventions for coronavirus disease 2019 (COVID-19) have been investigated by randomized controlled trials (RCTs). This systematic review and Bayesian network meta-analysis (NMA) aim to provide a comprehensive evaluation of efficacy of available treatments for COVID-19.MethodsWe searched for candidate COVID-19 studies in WHO COVID-19 Global Research Database, PubMed, PubMed Central, LitCovid, Proquest Central and Ovid up to December 19, 2020. RCTs for suspected or confirmed COVID-19 patients were included, regardless of publication status or demographic characteristics. Bayesian NMA with fixed effects was conducted to estimate the effect sizes using posterior means and 95% equal-tailed credible intervals (CrIs), while that with random effects was carried out as well for sensitivity analysis. Bayesian hierarchical models were used to estimate effect sizes of treatments grouped by their drug classifications.ResultsWe identified 96 eligible RCTs with a total of 51187 patients. Compared with the standard of care (SOC), this NMA showed that dexamethasone led to lower risk of mortality with an odds ratio (OR) of 0.85 (95% CrI [0.76, 0.95]; moderate certainty) and lower risk of mechanical ventilation (MV) with an OR of 0.68 (95% CrI [0.56, 0.83]; low certainty). For hospital discharge, remdesivir (OR 1.37, 95% CrI [1.15, 1.64]; moderate certainty), dexamethasone (OR 1.20, 95% CrI [1.08, 1.34]; low certainty), interferon beta (OR 2.15, 95% CrI [1.26, 3.74]; moderate certainty), tocilizumab (OR 1.40, 95% CrI [1.05, 1.89]; moderate certainty) and baricitinib plus remdesivir (OR 1.75, 95% CrI [1.28, 2.39]; moderate certainty) could all increase the discharge rate respectively. Recombinant human granulocyte colony-stimulating factor indicated lower risk of MV (OR 0.20, 95% CrI [0.10, 0.40]; moderate certainty); and patients receiving convalescent plasma resulted in better viral clearance (OR 2.28, 95% CrI [1.57, 3.34]; low certainty). About two-thirds of the studies included in this NMA were rated as high risk of bias, and the certainty of evidence was either low or very low for most of the comparisons.ConclusionThe Bayesian NMA identified superiority of several COVID-19 treatments over SOC in terms of mortality, requirement of MV, hospital discharge and viral clearance. These results provide a comprehensive comparison of current COVID-19 treatments and shed new light on further research and discovery of potential COVID-19 treatments.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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A Systematic Review and Network Meta-Analysis for COVID-19 Treatments

Zhang

Jin

Wen

et al. 2020

Preprint

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“…In addition, azithromycin possesses putative beneficial effects, such as antiviral and immunomodulation [11,12]. Nonetheless, large randomized clinical trials in United Kingdom and Brazil have failed to show the benefit of azithromycin in addition to standard care [13,14]. Oseltamivir was also given to this patient.…”

mentioning

confidence: 98%

Co-infection of COVID-19 and recurrent malaria

Pusparani¹,

Henrina

Cahyadi

2021

J Infect Dev Ctries

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In tropical countries, endemic diseases such as malaria can be challenging to distinguish from COVID-19 because of the similarities in presenting symptoms. Here we reported a case of a young soldier with fever and myalgia six days before admission, with non-productive cough, chills, nausea and vomiting, dizziness, and headache for two days. Previously, he had experienced four times of malaria infection. He had a history of positive non-falciparum malaria rapid diagnostic test (RDT) two days before admission. Significant findings were epigastric tenderness, splenomegaly, and severe thrombocytopenia of 36×103 cells / µL. A naso-oropharyngeal swab examination revealed a positive SARS-CoV-2 infection. Consequently, he was hospitalized for 12 days, successfully treated, and discharged without sequelae. Thus, in light of a pandemic, physicians need to raise the suspicion of concurrent COVID-19 infection with other tropical diseases, especially at-risk patients, because malaria and COVID-19 may share similar manifestations. Moreover, further ancillary testing, such as RDT, may be warranted.

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Association of Convalescent Plasma Treatment With Clinical Outcomes in Patients With COVID-19

Janiaud

Axfors

Schmitt

et al. 2021

JAMA

230

225

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IMPORTANCE Convalescent plasma is a proposed treatment for COVID-19.OBJECTIVE To assess clinical outcomes with convalescent plasma treatment vs placebo or standard of care in peer-reviewed and preprint publications or press releases of randomized clinical trials (RCTs).DATA SOURCES PubMed, the Cochrane COVID-19 trial registry, and the Living Overview of Evidence platform were searched until January 29, 2021. STUDY SELECTIONThe RCTs selected compared any type of convalescent plasma vs placebo or standard of care for patients with confirmed or suspected COVID-19 in any treatment setting. DATA EXTRACTION AND SYNTHESISTwo reviewers independently extracted data on relevant clinical outcomes, trial characteristics, and patient characteristics and used the Cochrane Risk of Bias Assessment Tool. The primary analysis included peer-reviewed publications of RCTs only, whereas the secondary analysis included all publicly available RCT data (peer-reviewed publications, preprints, and press releases). Inverse variance-weighted meta-analyses were conducted to summarize the treatment effects. The certainty of the evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation. MAIN OUTCOMES AND MEASURESAll-cause mortality, length of hospital stay, clinical improvement, clinical deterioration, mechanical ventilation use, and serious adverse events.RESULTS A total of 1060 patients from 4 peer-reviewed RCTs and 10 722 patients from 6 other publicly available RCTs were included. The summary risk ratio (RR) for all-cause mortality with convalescent plasma in the 4 peer-reviewed RCTs was 0.93 (95% CI, 0.63 to 1.38), the absolute risk difference was −1.21% (95% CI, −5.29% to 2.88%), and there was low certainty of the evidence due to imprecision. Across all 10 RCTs, the summary RR was 1.02 (95% CI, 0.92 to 1.12) and there was moderate certainty of the evidence due to inclusion of unpublished data. Among the peer-reviewed RCTs, the summary hazard ratio was 1.17 (95% CI, 0.07 to 20.34) for length of hospital stay, the summary RR was 0.76 (95% CI, 0.20 to 2.87) for mechanical ventilation use (the absolute risk difference for mechanical ventilation use was −2.56% [95% CI, −13.16% to 8.05%]), and there was low certainty of the evidence due to imprecision for both outcomes. Limited data on clinical improvement, clinical deterioration, and serious adverse events showed no significant differences. CONCLUSIONS AND RELEVANCETreatment with convalescent plasma compared with placebo or standard of care was not significantly associated with a decrease in all-cause mortality or with any benefit for other clinical outcomes. The certainty of the evidence was low to moderate for all-cause mortality and low for other outcomes.

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Azithromycin in Hospitalised Patients with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Cited by 18 publications

References 25 publications

A Systematic Review and Network Meta-Analysis for COVID-19 Treatments

A Systematic Review and Network Meta-Analysis for COVID-19 Treatments

Co-infection of COVID-19 and recurrent malaria

Association of Convalescent Plasma Treatment With Clinical Outcomes in Patients With COVID-19

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