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Dr K K Aggarwal, President Confederation of Medical Associations of Asia and Oceania, HCFI, Past National President IMA, Chief Editor Medtalks
(With inputs from Dr Monica Vasudev)
India
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New Delhi, May 24, 2020 :
For hospitalized patients with severe COVID-19, start remdesevir if available (Grade 1C).
Remdesivir for the Treatment of Covid-19 : Preliminary Report :
A double-blind, randomized, placebo-controlled trial of intravenous remdesivir in adults hospitalized with Covid-19 with evidence of lower respiratory tract involvement. 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.
A total of 1063 patients underwent randomization. The data and safety monitoring board recommended early unblinding of the results on the basis of findings from an analysis that showed shortened time to recovery in the remdesivir group. Preliminary results from the 1059 patients (538 assigned to remdesivir and 521 to placebo) with data available after randomization indicated that those who received remdesivir had a median recovery time of 11 days (95% confidence interval [CI], 9 to 12), as compared with 15 days (95% CI, 13 to 19) in those who received placebo (rate ratio for recovery, 1.32; 95% CI, 1.12 to 1.55; P<0.001). The Kaplan-Meier estimates of mortality by 14 days were 7.1% with remdesivir and 11.9% with placebo (hazard ratio for death, 0.70; 95% CI, 0.47 to 1.04). Serious adverse events were reported for 114 of the 541 patients in the remdesivir group who underwent randomization (21.1%) and 141 of the 522 patients in the placebo group who underwent randomization (27.0%).
CONCLUSIONS:
Remdesivir was superior to placebo in shortening the time to recovery in adults hospitalized with Covid-19 and evidence of lower respiratory tract infection. (Funded by the National Institute of Allergy and Infectious Diseases and others; New England Journal of Medicine].
In contrast, in a randomized trial from China of 237 patients with severe COVID-19, remdesivir and placebo had similar times to clinical improvement (median 21 versus 23 days) and mortality rates (14 versus 13 percent); however, confidence in the finding of no effect was reduced by use of concomitant therapies, differences in baseline comorbidities between the groups, and failure to meet the target enrollment
Remdesivir is a novel nucleotide analogue that has activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in vitro.
In the United States, the Food and Drug Administration (FDA) has issued an emergency use authorization for remdesivir for hospitalized children and adults with severe COVID-19 (SpO2 ≤94 percent on room air, requiring supplemental oxygen, mechanical ventilation, or extracorporeal membrane oxygenation [ECMO]).
The suggested adult dose is 200 mg intravenously on day 1 followed by 100 mg daily for 10 days total in patients on mechanical ventilation or ECMO and 5 days total in other patients (with extension to 10 days if there is no clinical improvement).
Remdesivir is not recommended in patients with an alanine aminotransferase ≥5 times the upper limit of normal (and should be discontinued if it rises above this level during treatment or if there are other signs of liver injury).
The pharmacokinetics of remdesivir in the setting of renal impairment are uncertain, and it is prepared in a cyclodextrin vehicle that accumulates in renal impairment and may be toxic; thus, remdesivir is not recommended in patients with an estimated glomerular filtration rate (eGFR) <30 mL/min per 1.73 m2 unless the potential benefit outweighs the potential risk.
Reported side effects include nausea, vomiting, and transaminase elevations. In a preliminary report from a trial of remdesevir among patients with severe COVID-19, grade 3 aminotransferase elevations occurred in 7 percent and led to drug discontinuation in 3 percent. Other adverse events described in patients who received remdesivir include worsening kidney injury, multiple organ failure, and worsened cardiopulmonary status.
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