Abstract We report the first long-term follow-up of a randomized trial (NCT04978259) addressing the effects of remdesivir on recovery (primary outcome) and other patient-important outcomes one year after hospitalization resulting from COVID-19. Of the 208 patients recruited from 11 Finnish hospitals, 198 survived, of whom 181 (92%) completed follow-up. At one year, self-reported recovery occurred in 85% in remdesivir and 86% in standard of care (SoC) (RR 0.94, 95% CI 0.47-1.90). We infer no convincing difference between remdesivir and SoC in quality of life or symptom outcomes ( p > 0.05). Of the 21 potential long-COVID symptoms, patients reported moderate/major bother from fatigue (26%), joint pain (22%), and problems with memory (19%) and attention/concentration (18%). In conclusion, after a one-year follow-up of hospitalized patients, one in six reported they had not recovered well from COVID-19. Our results provide no convincing evidence of remdesivir benefit, but wide confidence intervals included possible benefit and harm.
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.
Abstract Background Coronavirus disease 2019 (COVID-19) patients frequently suffer from long-term sequelae, often called “long COVID” or “post COVID-19 condition”. Remdesivir, given in early disease, decreases the risk of hospitalization and potentially mortality. No randomized trials have thus far published long-term follow-up data on any COVID-19 drug treatment. We investigated the effects of remdesivir on a range of patient-important outcomes at one year. Methods Between July 2020 and January 2021, an open-label randomized multicenter trial in Finland recruited 208 adult patients from 11 Finnish hospitals. Patients were randomly assigned (1:1 ratio) to standard of care (SoC)with remdesivir (median duration of remdesivir treatment 5 days) or SoC alone. Primary outcomes were self-reported recovery, exertional dyspnea, fatigue, and quality of life at one year. Secondary outcomes were overall mortality and several potential long-COVID symptoms. Results At one year, 5 (4.4%) of 114 patients in the remdesivir and 5 (5.3%) of 94 in the SoC group had died (RR 0.82, 95% CI 0.25-2.76; absolute difference: -0.9%, 95% CI -7.9-5.3); 181 (92% of survivors) completed the follow-up. Self-reported recovery (fully or largely) occurred in 85% in remdesivir and in 86% in SoC (RR 0.94, 0.47-1.90; absolute difference: -0.9%, 95% CI -11%-10%). Exertional dyspnea occurred in 5% in remdesivir and 8% in SoC (OR 0.61, 95% CI 0.20-1.85; absolute difference -3.3%, 95% CI -12%-4.4%). We found no convincing difference between remdesivir and SoC groups in quality of life or symptom outcomes (p > 0.05 for all). Of the 21 potential long-COVID symptoms, patients often reported moderate or major bother from fatigue (26%), joint pain (22%), persistent respiratory mucus (21%), and problems with memory (19%) and attention/concentration (18%) (Figure). Bother from potential long-COVID symptoms at one year from COVID-19 hospitalization between the standard of care and standard of care plus remdesivir groups. Conclusion After a one-year follow-up of hospitalized patients (with a very high participation rate), approximately one in four reported substantial bother from fatigue, and one in six reported that they had not recovered well from COVID-19. We found no convincing evidence of a remdesivir effect, but confidence intervals were wide and included possible substantial benefit and substantial harm. Disclosures Hanna-Riikka Kreivi, MD, PhD, Pfizer: Advisor/Consultant|Roche: Advisor/Consultant Tuomas Rosberg, MD, PhD, AstraZeneca: Honoraria|Boehringer-Ingelheim: Honoraria|GSK: Honoraria.
Abstract We report the short- and long-term results of the SOLIDARITY Finland on mortality and other patient-important outcomes in patients hospitalised for COVID-19. Between 08/2021 and 03/2023, we randomised 156 patients in 15 hospitals. In the imatinib group, 7.2% of patients had died at 30 days and 13.3% at 1 year and in the standard of care group 4.1% and 8.3% (adjusted HR at 30 days 1.09, 95% CI 0.23–5.07). In a meta-analysis of randomised trials of imatinib versus standard of care (n=732), allocation to imatinib was associated with a mortality risk ratio of 0.73 (95% CI 0.32–1.63). At 1-year, self-reported recovery occurred in 79.0% in imatinib and in 88.3% in standard of care (RR 0.91, 95% CI 0.78-1.06). Of the 21 potential long COVID symptoms, patients often reported moderate or major bother from fatigue (24%), sleeping problems (19%) and memory difficulties (17%). We found no convincing difference between imatinib and standard of care groups in quality of life or symptom outcomes. The evidence raises serious doubts regarding the benefit of imatinib in reducing mortality, improving recovery, and preventing potential long COVID symptoms when given to patients hospitalised for COVID-19.
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