Final results of the DisCoVeRy trial of remdesivir for patients admitted to hospital with COVID-19.
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ABSTRACT:
SUBMITTER: Ader F
PROVIDER: S-EPMC9132543 | biostudies-literature | 2022 Jun
REPOSITORIES: biostudies-literature
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Final results of the DisCoVeRy trial of remdesivir for patients admitted to hospital with COVID-19.
Ader Florence F Bouscambert-Duchamp Maude M Hites Maya M Peiffer-Smadja Nathan N Mentré France F Burdet Charles C
The Lancet. Infectious diseases 20220601 6
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| S-EPMC8439621 | biostudies-literature
Project description:BackgroundThe Solidarity trial among COVID-19 inpatients has previously reported interim mortality analyses for four repurposed antiviral drugs. Lopinavir, hydroxychloroquine, and interferon (IFN)-β1a were discontinued for futility but randomisation to remdesivir continued. Here, we report the final results of Solidarity and meta-analyses of mortality in all relevant trials to date.MethodsSolidarity enrolled consenting adults (aged ≥18 years) recently hospitalised with, in the view of their doctor, definite COVID-19 and no contraindication to any of the study drugs, regardless of any other patient characteristics. Participants were randomly allocated, in equal proportions between the locally available options, to receive whichever of the four study drugs (lopinavir, hydroxychloroquine, IFN-β1a, or remdesivir) were locally available at that time or no study drug (controls). All patients also received the local standard of care. No placebos were given. The protocol-specified primary endpoint was in-hospital mortality, subdivided by disease severity. Secondary endpoints were progression to ventilation if not already ventilated, and time-to-discharge from hospital. Final log-rank and Kaplan-Meier analyses are presented for remdesivir, and are appended for all four study drugs. Meta-analyses give weighted averages of the mortality findings in this and all other randomised trials of these drugs among hospital inpatients. Solidarity is registered with ISRCTN, ISRCTN83971151, and ClinicalTrials.gov, NCT04315948.FindingsBetween March 22, 2020, and Jan 29, 2021, 14 304 potentially eligible patients were recruited from 454 hospitals in 35 countries in all six WHO regions. After the exclusion of 83 (0·6%) patients with a refuted COVID-19 diagnosis or encrypted consent not entered into the database, Solidarity enrolled 14 221 patients, including 8275 randomly allocated (1:1) either to remdesivir (ten daily infusions, unless discharged earlier) or to its control (allocated no study drug although remdesivir was locally available). Compliance was high in both groups. Overall, 602 (14·5%) of 4146 patients assigned to remdesivir died versus 643 (15·6%) of 4129 assigned to control (mortality rate ratio [RR] 0·91 [95% CI 0·82-1·02], p=0·12). Of those already ventilated, 151 (42·1%) of 359 assigned to remdesivir died versus 134 (38·6%) of 347 assigned to control (RR 1·13 [0·89-1·42], p=0·32). Of those not ventilated but on oxygen, 14·6% assigned to remdesivir died versus 16·3% assigned to control (RR 0·87 [0·76-0·99], p=0·03). Of 1730 not on oxygen initially, 2·9% assigned to remdesivir died versus 3·8% assigned to control (RR 0·76 [0·46-1·28], p=0·30). Combining all those not ventilated initially, 11·9% assigned to remdesivir died versus 13·5% assigned to control (RR 0·86 [0·76-0·98], p=0·02) and 14·1% versus 15·7% progressed to ventilation (RR 0·88 [0·77-1·00], p=0·04). The non-prespecified composite outcome of death or progression to ventilation occurred in 19·6% assigned to remdesivir versus 22·5% assigned to control (RR 0·84 [0·75-0·93], p=0·001). Allocation to daily remdesivir infusions (vs open-label control) delayed discharge by about 1 day during the 10-day treatment period. A meta-analysis of mortality in all randomised trials of remdesivir versus no remdesivir yielded similar findings.InterpretationRemdesivir has no significant effect on patients with COVID-19 who are already being ventilated. Among other hospitalised patients, it has a small effect against death or progression to ventilation (or both).FundingWHO.
| S-EPMC9060606 | biostudies-literature
Project description:BackgroundAlthough several therapeutic agents have been evaluated for the treatment of coronavirus disease 2019 (Covid-19), no antiviral agents have yet been shown to be efficacious.MethodsWe conducted a double-blind, randomized, placebo-controlled trial of intravenous remdesivir in adults who were hospitalized with Covid-19 and had evidence of lower respiratory tract infection. Patients were randomly assigned to receive either remdesivir (200 mg loading dose on day 1, followed by 100 mg daily for up to 9 additional days) or placebo for up to 10 days. The primary outcome was the time to recovery, defined by either discharge from the hospital or hospitalization for infection-control purposes only.ResultsA total of 1062 patients underwent randomization (with 541 assigned to remdesivir and 521 to placebo). Those who received remdesivir had a median recovery time of 10 days (95% confidence interval [CI], 9 to 11), as compared with 15 days (95% CI, 13 to 18) among those who received placebo (rate ratio for recovery, 1.29; 95% CI, 1.12 to 1.49; P<0.001, by a log-rank test). In an analysis that used a proportional-odds model with an eight-category ordinal scale, the patients who received remdesivir were found to be more likely than those who received placebo to have clinical improvement at day 15 (odds ratio, 1.5; 95% CI, 1.2 to 1.9, after adjustment for actual disease severity). The Kaplan-Meier estimates of mortality were 6.7% with remdesivir and 11.9% with placebo by day 15 and 11.4% with remdesivir and 15.2% with placebo by day 29 (hazard ratio, 0.73; 95% CI, 0.52 to 1.03). Serious adverse events were reported in 131 of the 532 patients who received remdesivir (24.6%) and in 163 of the 516 patients who received placebo (31.6%).ConclusionsOur data show that remdesivir was superior to placebo in shortening the time to recovery in adults who were hospitalized with Covid-19 and had evidence of lower respiratory tract infection. (Funded by the National Institute of Allergy and Infectious Diseases and others; ACTT-1 ClinicalTrials.gov number, NCT04280705.).
| S-EPMC7262788 | biostudies-literature
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| S-BSST647 | biostudies-other
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| S-EPMC7799042 | biostudies-literature
Project description:We isolated neutrophils from 11 healthy controls, 12 COIVD-19 patients in ICU and 12 COVID-19 patients from ward and submitted the isolated RNA for RNA sequencing. We then performed gene expression profiling analysis using data obtained from RNA-seq of 3 different cohorts. .
2024-06-01 | GSE234207 | GEO
Project description:BackgroundThe role of remdesivir in the treatment of patients in hospital with COVID-19 remains ill defined in a global context. The World Health Organization Solidarity randomized controlled trial (RCT) evaluated remdesivir in patients across many countries, with Canada enrolling patients using an expanded data collection format in the Canadian Treatments for COVID-19 (CATCO) trial. We report on the Canadian findings, with additional demographics, characteristics and clinical outcomes, to explore the potential for differential effects across different health care systems.MethodsWe performed an open-label, pragmatic RCT in Canadian hospitals, in conjunction with the Solidarity trial. We randomized patients to 10 days of remdesivir (200 mg intravenously [IV] on day 0, followed by 100 mg IV daily), plus standard care, or standard care alone. The primary outcome was in-hospital mortality. Secondary outcomes included changes in clinical severity, oxygen- and ventilator-free days (at 28 d), incidence of new oxygen or mechanical ventilation use, duration of hospital stay, and adverse event rates. We performed a priori subgroup analyses according to duration of symptoms before enrolment, age, sex and severity of symptoms on presentation.ResultsAcross 52 Canadian hospitals, we randomized 1282 patients between Aug. 14, 2020, and Apr. 1, 2021, to remdesivir (n = 634) or standard of care (n = 648). Of these, 15 withdrew consent or were still in hospital, for a total sample of 1267 patients. Among patients assigned to receive remdesivir, in-hospital mortality was 18.7%, compared with 22.6% in the standard-of-care arm (relative risk [RR] 0.83 (95% confidence interval [CI] 0.67 to 1.03), and 60-day mortality was 24.8% and 28.2%, respectively (95% CI 0.72 to 1.07). For patients not mechanically ventilated at baseline, the need for mechanical ventilation was 8.0% in those assigned remdesivir, and 15.0% in those receiving standard of care (RR 0.53, 95% CI 0.38 to 0.75). Mean oxygen-free and ventilator-free days at day 28 were 15.9 (± standard deviation [SD] 10.5) and 21.4 (± SD 11.3) in those receiving remdesivir and 14.2 (± SD 11) and 19.5 (± SD 12.3) in those receiving standard of care (p = 0.006 and 0.007, respectively). There was no difference in safety events of new dialysis, change in creatinine, or new hepatic dysfunction between the 2 groups.InterpretationRemdesivir, when compared with standard of care, has a modest but significant effect on outcomes important to patients and health systems, such as the need for mechanical ventilation. Trial registration: ClinicalTrials.gov, no. NCT04330690.
| S-EPMC8863204 | biostudies-literature
Project description:BackgroundColchicine has been proposed as a treatment for COVID-19 based on its anti-inflammatory actions. We aimed to evaluate the efficacy and safety of colchicine in patients admitted to hospital with COVID-19.MethodsIn this streamlined, randomised, controlled, open-label trial, underway at 177 hospitals in the UK, two hospitals in Indonesia, and two hospitals in Nepal, several possible treatments were compared with usual care in patients hospitalised with COVID-19. Patients were eligible for inclusion in the study if they were admitted to hospital with clinically suspected or laboratory confirmed SARS-CoV-2 infection and had no medical history that might, in the opinion of the attending clinician, put the patient at significant risk if they were to participate in the trial. Eligible and consenting adults were randomly assigned (1:1) to receive either usual standard of care alone (usual care group) or usual standard of care plus colchicine (colchicine group) using web-based simple (unstratified) randomisation with allocation concealment. Participants received colchicine 1 mg after randomisation followed by 500 μg 12 h later and then 500 μg twice a day by mouth or nasogastric tube for 10 days in total or until discharge. Dose frequency was halved for patients receiving a moderate CYP3A4 inhibitor (eg, diltiazem), patients with an estimated glomerular filtration rate of less than 30 mL/min per 1·73m2, and those with an estimated bodyweight of less than 70 kg. The primary outcome was 28-day mortality, secondary endpoints included time to discharge, the proportion of patients discharged from hospital within 28 days, and, in patients not on invasive mechanical ventilation at randomisation, a composite endpoint of invasive mechanical ventilation or death. All analyses were by intention-to-treat. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.FindingsBetween Nov 27, 2020, and March 4, 2021, 11 340 (58%) of 19 423 patients enrolled into the RECOVERY trial were eligible to receive colchicine; 5610 (49%) patients were randomly assigned to the colchicine group and 5730 (51%) to the usual care group. Overall, 1173 (21%) patients in the colchicine group and 1190 (21%) patients in the usual care group died within 28 days (rate ratio 1·01 [95% CI 0·93 to 1·10]; p=0·77). Consistent results were seen in all prespecified subgroups of patients. Median time to discharge alive (10 days [IQR 5 to >28]) was the same in both groups, and there was no significant difference in the proportion of patients discharged from hospital alive within 28 days (3901 [70%] patients in the colchicine group and 4032 [70%] usual care group; rate ratio 0·98 [95% CI 0·94 to 1·03]; p=0·44). In those not on invasive mechanical ventilation at baseline, there was no significant difference in the proportion meeting the composite endpoint of invasive mechanical ventilation or death (1344 [25%] in the colchicine group vs 1343 [25%] patients in the usual care group; risk ratio 1·02 [95% CI 0·96 to 1·09]; p=0·47).InterpretationIn adults hospitalised with COVID-19, colchicine was not associated with reductions in 28-day mortality, duration of hospital stay, or risk of progressing to invasive mechanical ventilation or death.FundingUK Research and Innovation (Medical Research Council), National Institute of Health Research, and Wellcome Trust.
| S-EPMC8523117 | biostudies-literature
Project description:BackgroundEmpagliflozin has been proposed as a treatment for COVID-19 on the basis of its anti-inflammatory, metabolic, and haemodynamic effects. The RECOVERY trial aimed to assess its safety and efficacy in patients admitted to hospital with COVID-19.MethodsIn the randomised, controlled, open-label RECOVERY trial, several possible treatments are compared with usual care in patients hospitalised with COVID-19. In this analysis, we assess eligible and consenting adults who were randomly allocated in a 1:1 ratio to either usual standard of care alone or usual standard of care plus oral empagliflozin 10 mg once daily for 28 days or until discharge (whichever came first) using web-based simple (unstratified) randomisation with allocation concealment. The primary outcome was 28-day mortality; secondary outcomes were duration of hospitalisation and (among participants not on invasive mechanical ventilation at baseline) the composite of invasive mechanical ventilation or death. On March 3, 2023 the independent data monitoring committee recommended that the investigators review the data and recruitment was consequently stopped on March 7, 2023. The ongoing RECOVERY trial is registered with ISRCTN (50189673) and ClinicalTrials.gov (NCT04381936).FindingsBetween July 28, 2021 and March 6, 2023, 4271 patients were randomly allocated to receive either empagliflozin (2113 patients) or usual care alone (2158 patients). Primary and secondary outcome data were known for greater than 99% of randomly assigned patients. Overall, 289 (14%) of 2113 patients allocated to empagliflozin and 307 (14%) of 2158 patients allocated to usual care died within 28 days (rate ratio 0·96 [95% CI 0·82-1·13]; p=0·64). There was no evidence of significant differences in duration of hospitalisation (median 8 days for both groups) or the proportion of patients discharged from hospital alive within 28 days (1678 [79%] in the empagliflozin group vs 1677 [78%] in the usual care group; rate ratio 1·03 [95% CI 0·96-1·10]; p=0·44). Among those not on invasive mechanical ventilation at baseline, there was no evidence of a significant difference in the proportion meeting the composite endpoint of invasive mechanical ventilation or death (338 [16%] of 2084 vs 371 [17%] of 2143; risk ratio 0·95 [95% CI 0·84-1·08]; p=0·44). Two serious adverse events believed to be related to empagliflozin were reported: both were ketosis without acidosis.InterpretationIn adults hospitalised with COVID-19, empagliflozin was not associated with reductions in 28-day mortality, duration of hospital stay, or risk of progressing to invasive mechanical ventilation or death so is not indicated for the treatment of such patients unless there is an established indication due to a different condition such as diabetes.FundingUK Research and Innovation (Medical Research Council) and National Institute of Health Research (MC_PC_19056), and Wellcome Trust (222406/Z/20/Z).TranslationsFor the Nepali, Hindi, Indonesian (Bahasa) and Vietnamese translations of the abstract see Supplementary Materials section.
| S-EPMC10957483 | biostudies-literature
Project description:BackgroundIn this study, we aimed to evaluate the effects of tocilizumab in adult patients admitted to hospital with COVID-19 with both hypoxia and systemic inflammation.MethodsThis randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing several possible treatments in patients hospitalised with COVID-19 in the UK. Those trial participants with hypoxia (oxygen saturation <92% on air or requiring oxygen therapy) and evidence of systemic inflammation (C-reactive protein ≥75 mg/L) were eligible for random assignment in a 1:1 ratio to usual standard of care alone versus usual standard of care plus tocilizumab at a dose of 400 mg-800 mg (depending on weight) given intravenously. A second dose could be given 12-24 h later if the patient's condition had not improved. The primary outcome was 28-day mortality, assessed in the intention-to-treat population. The trial is registered with ISRCTN (50189673) and ClinicalTrials.gov (NCT04381936).FindingsBetween April 23, 2020, and Jan 24, 2021, 4116 adults of 21 550 patients enrolled into the RECOVERY trial were included in the assessment of tocilizumab, including 3385 (82%) patients receiving systemic corticosteroids. Overall, 621 (31%) of the 2022 patients allocated tocilizumab and 729 (35%) of the 2094 patients allocated to usual care died within 28 days (rate ratio 0·85; 95% CI 0·76-0·94; p=0·0028). Consistent results were seen in all prespecified subgroups of patients, including those receiving systemic corticosteroids. Patients allocated to tocilizumab were more likely to be discharged from hospital within 28 days (57% vs 50%; rate ratio 1·22; 1·12-1·33; p<0·0001). Among those not receiving invasive mechanical ventilation at baseline, patients allocated tocilizumab were less likely to reach the composite endpoint of invasive mechanical ventilation or death (35% vs 42%; risk ratio 0·84; 95% CI 0·77-0·92; p<0·0001).InterpretationIn hospitalised COVID-19 patients with hypoxia and systemic inflammation, tocilizumab improved survival and other clinical outcomes. These benefits were seen regardless of the amount of respiratory support and were additional to the benefits of systemic corticosteroids.FundingUK Research and Innovation (Medical Research Council) and National Institute of Health Research.
| S-EPMC8084355 | biostudies-literature