key: cord-0997277-uxcmcinv
authors: Kaka, Anjum S.; MacDonald, Roderick; Linskens, Eric J.; Wilt, Timothy J.
title: Update Alert: Remdesivir for Adults With COVID-19
date: 2021-06-15
journal: Ann Intern Med
DOI: 10.7326/l21-0375
sha: b9a03d482877d0d6396e91227cf8100a405e7dbb
doc_id: 997277
cord_uid: uxcmcinv

nan

Exclusion criteria: Women who were pregnant or breast feeding infants, ALT or AST >5 times the upper limit of the normal range; creatinine clearance < 50 mL/min using the Cockcroft-Gault formula for participants ≥ 18 years of age and Schwartz Formula for participants < 18 years of age; mechanically ventilated at screening; concurrent treatment or planned concurrent treatment with other agents with actual or possible direct acting antiviral activity against SARS-CoV-2; participation in any other clinical trial of an experimental treatment for COVID-19 Inclusion criteria: men and non-pregnant women with COVID-19, age at least 18 years, RT-PCR positive for SARS-CoV-2, pneumonia confirmed by chest imaging, oxygen saturation of 94% or lower on room air or a ratio of arterial oxygen partial pressure to fractional inspired oxygen of 300 mm Hg or less, within 12 days of symptom onset Exclusion criteria: pregnancy or breast feeding; hepatic cirrhosis; ALT or AST >5 times the upper limit of the normal range; known severe renal impairment (estimated eGFR<30 mL/min per 1·73 m²) or receipt of continuous renal replacement therapy, hemodialysis, or peritoneal dialysis; enrolment into an investigational treatment study for COVID-19 in the 30 days before screening Inclusion criteria: patients ≥ 18 years (at all sites), or aged ≥ 12 and < 18 years of age weighing ≥ 40 kg (where permitted according to local law) currently hospitalized with SARS-CoV-2 infection confirmed by PCR test ≤ 4 days before randomization; radiographic evidence of pulmonary infiltrates and peripheral capillary oxygen saturation (SpO2) ≤ 94% or requiring supplemental oxygen at screening Exclusion criteria: Pregnant or women who were breast feeding infants, ALT or AST >5 times the upper limit of the normal range, creatinine clearance < 50 mL/min using the Cockcroft-Gault formula for participants ≥ 18 years of age and Schwartz Formula for participants < 18 years of age; mechanically ventilated (including V-V ECMO) ≥ 5 days, or any duration of V-A ECMO; evidence of multiorgan failure; concurrent treatment with other agents with actual or possible direct acting antiviral activity against SARS-CoV-2 < 24 hours prior to study drug dosing; participant in any other clinical trial of an experimental treatment for COVID-19

Study Period/Length of Follow-up: 14 days (up to 30 days for adverse events)

White 70% Black 11% Asian 11% Other 7%

Time from symptom onset to drug Remdesivir 5-day median [IQR] 8 days [5] [6] [7] [8] [9] [10] [11] Remdesivir 10-day median [IQR] 9 days [6] [7] [8] [9] [10] [11] [12] Oxygen status on admission: Percent on no oxygen 14% Percent on supplemental oxygen 55% Percent on non-invasive ventilation 27% Percent on invasive ventilation 4% ALT = alanine aminotransferase; AST = aspartate aminotransferase; ECMO = extracorporeal membrane oxygenation; eGFR = estimated glomerular filtration rate; IQR = interquartile range; RT-PCR = reverse transcription, polymerase-chain-reaction; SARS-CoV = Severe Acute Respiratory Syndrome Coronavirus-2 infection * Indicates newly identified trial Supplement Clinical improvement, defined as a two-point reduction in patients' admission status on a 6-point ordinal scale (1= live discharge to 6=death), or live discharge from the hospital, whichever came first (4) as an improvement of at least 2 points from baseline on 7-point ordinal scale (1=death to 7=discharged from hospital) (3,6) Remdesivir 10-day course versus placebo (4) or standard of care (3); 2 trials (n=629)

WHO Solidarity Trial Consortium. Repurposed antiviral drugs for Covid-19 -interim WHO Solidarity Trial Results

Remdesivir for the treatment of Covid-19 -final report

Effect of remdesivir vs standard care on clinical status at 11 days in patients with moderate COVID-19. A randomized clinical trial

Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial

Clinical outcomes of using remdesivir in patients with moderate to severe COVID-19: A prospective randomised study

Remdesivir for 5 or 10 days in patients with severe Covid-19

 2% (-7.0 to 19.4) Insufficient ‖‖

Remdesivir 

Remdesivir 10-day course versus placebo or standard of care; 3 trials (n=1674) (2, 3, 4) 11-29 days Any severity -No O2 28%; Any O2/Ventilation 72% (5), assessed as high risk of bias, did not impact the overall certainty of evidence or magnitude of effect ¶ Downgraded two levels for study limitations and imprecision (wide CIs) ** Downgraded two levels for imprecision and inconsistency † † Downgraded two levels for difficulty in interpreting precision and inconsistency. ‡ ‡ Downgraded to insufficient for difficulty in interpreting results (HR not reported for 5-day vs.10 day) and higher median with 10-day vs standard of care but reduction in time to recovery favors 10-day based on HR § § Downgraded two levels for imprecision and inconsistency ‖‖ Downgraded to insufficient for study limitations and imprecision (very wide CIs)