Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial
et al., Lancet, doi:10.1016/S0140-6736(20)31022-9, Apr 2020
Small RCT with 237 hospitalized patients in China with severe COVID-19, not showing statistically significant benefits. 158 treatment patients and 79 control patients.
While too small for significance, the subgroup treated within 10 days showed reduced mortality RR 0.76, p = 0.58, and reduced median time to clinical improvement of 18 days vs. 23 days, hazard ratio 1.52 [0.95-2.43].
Gérard, Zhou, Wu, Kamo, Choi, Kim show increased risk of acute kidney injury, Leo, Briciu, Muntean, Petrov show increased risk of liver injury, and Negru, Cheng, Mohammed show increased risk of cardiac disorders with remdesivir.
Standard of Care (SOC) for COVID-19 in the study country,
China, is average with moderate efficacy for approved treatments14.
|
all patients, 8.6% higher, RR 1.09, p = 1.00, treatment 22 of 158 (13.9%), control 10 of 78 (12.8%), day 28.
|
|
<10 days from symptoms, 24.3% lower, RR 0.76, p = 0.58, treatment 8 of 71 (11.3%), control 7 of 47 (14.9%), NNT 28, day 28.
|
|
>10 days from symptoms, 47.6% higher, RR 1.48, p = 0.76, treatment 12 of 84 (14.3%), control 3 of 31 (9.7%), day 28.
|
| Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates |
1.
Gérard et al., Remdesivir and Acute Renal Failure: A Potential Safety Signal From Disproportionality Analysis of the WHO Safety Database, Clinical Pharmacology & Therapeutics, doi:10.1002/cpt.2145.
2.
Zhou et al., Acute Kidney Injury and Drugs Prescribed for COVID-19 in Diabetes Patients: A Real-World Disproportionality Analysis, Frontiers in Pharmacology, doi:10.3389/fphar.2022.833679.
3.
Wu et al., Acute Kidney Injury Associated With Remdesivir: A Comprehensive Pharmacovigilance Analysis of COVID-19 Reports in FAERS, Frontiers in Pharmacology, doi:10.3389/fphar.2022.692828.
4.
Kamo et al., Association of Antiviral Drugs for the Treatment of COVID-19 With Acute Renal Failure, In Vivo, doi:10.21873/invivo.13637.
5.
Choi et al., Comparative effectiveness of combination therapy with nirmatrelvir–ritonavir and remdesivir versus monotherapy with remdesivir or nirmatrelvir–ritonavir in patients hospitalised with COVID-19: a target trial emulation study, The Lancet Infectious Diseases, doi:10.1016/S1473-3099(24)00353-0.
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Kim et al., Investigating the Safety Profile of Fast‐Track COVID‐19 Drugs Using the FDA Adverse Event Reporting System Database: A Comparative Observational Study, Pharmacoepidemiology and Drug Safety, doi:10.1002/pds.70043.
7.
Leo et al., Hepatocellular liver injury in hospitalized patients affected by COVID-19: Presence of different risk factors at different time points, Digestive and Liver Disease, doi:10.1016/j.dld.2021.12.014.
8.
Briciu et al., Evolving Clinical Manifestations and Outcomes in COVID-19 Patients: A Comparative Analysis of SARS-CoV-2 Variant Waves in a Romanian Hospital Setting, Pathogens, doi:10.3390/pathogens12121453.
9.
Muntean et al., Effects of COVID-19 on the Liver and Mortality in Patients with SARS-CoV-2 Pneumonia Caused by Delta and Non-Delta Variants: An Analysis in a Single Centre, Pharmaceuticals, doi:10.3390/ph17010003.
10.
Petrov et al., The Effect of Potentially Hepatotoxic Medicinal Products on Alanine Transaminase Levels in COVID-19 Patients: A Case–Control Study, Safety and Risk of Pharmacotherapy, doi:10.30895/2312-7821-2025-458.
11.
Negru et al., Comparative Pharmacovigilance Analysis of Approved and Repurposed Antivirals for COVID-19: Insights from EudraVigilance Data, Biomedicines, doi:10.3390/biomedicines13061387.
12.
Cheng et al., Cardiovascular Safety of COVID-19 Treatments: A Disproportionality Analysis of Adverse Event Reports from the WHO VigiBase, Infectious Diseases and Therapy, doi:10.1007/s40121-025-01225-z.
Wang et al., 29 Apr 2020, Randomized Controlled Trial, China, peer-reviewed, 46 authors, study period 6 February, 2020 - 12 March, 2020, average treatment delay 11.0 days.
Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial
The Lancet, doi:10.1016/s0140-6736(20)31022-9
Background No specific antiviral drug has been proven effective for treatment of patients with severe coronavirus disease 2019 (COVID-19). Remdesivir (GS-5734), a nucleoside analogue prodrug, has inhibitory effects on pathogenic animal and human coronaviruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in vitro, and inhibits Middle East respiratory syndrome coronavirus, SARS-CoV-1, and SARS-CoV-2 replication in animal models. Methods We did a randomised, double-blind, placebo-controlled, multicentre trial at ten hospitals in Hubei, China. Eligible patients were adults (aged ≥18 years) admitted to hospital with laboratory-confirmed SARS-CoV-2 infection, with an interval from symptom onset to enrolment of 12 days or less, oxygen saturation of 94% or less on room air or a ratio of arterial oxygen partial pressure to fractional inspired oxygen of 300 mm Hg or less, and radiologically confirmed pneumonia. Patients were randomly assigned in a 2:1 ratio to intravenous remdesivir (200 mg on day 1 followed by 100 mg on days 2-10 in single daily infusions) or the same volume of placebo infusions for 10 days. Patients were permitted concomitant use of lopinavir-ritonavir, interferons, and corticosteroids. The primary endpoint was time to clinical improvement up to day 28, defined as the time (in days) from randomisation to the point of a decline of two levels on a six-point ordinal scale of clinical status (from 1=discharged to 6=death) or discharged alive from hospital, whichever came first. Primary analysis was done in the intention-to-treat (ITT) population and safety analysis was done in all patients who started their assigned treatment. This trial is registered with ClinicalTrials.gov, NCT04257656.
with a previous study of compassionate use of remdesivir, 21 our study population was less ill (eg, at the time of enrolment, 0•4% were on invasive mechanical ventilation or extracorporeal membrane oxygenation vs 64% in the previous study) and was treated somewhat earlier in their disease course (median 10 days vs 12 days). Such differences might be expected to favour remdesivir, providing greater effects in our study population, but our results did not meet this expectation. However, our study did not reach its target enrolment because the stringent public health measures used in Wuhan led to marked reductions in new patient presentations in mid-March, and restrictions on hospital bed availability resulted in most patients being enrolled later in the course of disease. Consequently, we could not adequately assess whether earlier remdesivir treatment might have provided clinical benefit. However, among patients who
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Late treatment
is less effective
is less effective
