Remdesivir for 5 or 10 Days in Patients with Severe Covid-19

Abstract

Background Remdesivir is an RNA polymerase inhibitor with potent antiviral activity in vitro and efficacy in animal models of coronavirus disease 2019 (Covid-19). Methods We conducted a randomized, open-label, phase 3 trial involving hospitalized patients with confirmed SARS-CoV-2 infection, oxygen saturation of 94% or less while they were breathing ambient air, and radiologic evidence of pneumonia. Patients were randomly assigned in a 1:1 ratio to receive intravenous remdesivir for either 5 days or 10 days. All patients received 200 mg of remdesivir on day 1 and 100 mg once daily on subsequent days. The primary end point was clinical status on day 14, assessed on a 7-point ordinal scale. Results In total, 397 patients underwent randomization and began treatment (200 patients for 5 days and 197 for 10 days). The median duration of treatment was 5 days (interquartile range, 5 to 5) in the 5-day group and 9 days (interquartile range, 5 to 10) in the 10-day group. At baseline, patients randomly assigned to the 10-day group had significantly worse clinical status than those assigned to the 5-day group (P=0.02). By day 14, a clinical improvement of 2 points or more on the ordinal scale occurred in 64% of patients in the 5-day group and in 54% in the 10-day group. After adjustment for baseline clinical status, patients in the 10-day group had a distribution in clinical status at day 14 that was similar to that among patients in the 5-day group (P=0.14). The most common adverse events were nausea (9% of patients), worsening respiratory failure (8%), elevated alanine aminotransferase level (7%), and constipation (7%). Conclusions In patients with severe Covid-19 not requiring mechanical ventilation, our trial did not show a significant difference between a 5-day course and a 10-day course of remdesivir. With no placebo control, however, the magnitude of benefit cannot be determined. (Funded by Gilead Sciences; GS-US-540-5773 ClinicalTrials.gov number, NCT04292899 .)

Safety, Tolerability, and Pharmacokinetics of Remdesivir, An Antiviral for Treatment of COVID‐19, in Healthy Subjects

“…On May 1, 2020, based on available data from two global clinical trials, the US Food and Drug Administration (FDA) granted emergency use authorization to allow RDV to treat adults and children hospitalized with severe COVID‐19 19,22,23 . Based on these clinical data, RDV has been approved for the treatment of adults and pediatric patients in Japan 24 .…”

Combination Therapy With Remdesivir, Dexamethasone, and Tocilizumab in Patients With Severe Corona Virus Disease 2019 in Clinical Practice

“…Moreover, it was found to have antiviral activity against single-stranded RNA viruses such as Middle East respiratory syndrome coronavirus, SARS-CoV, and SARS-CoV-2. This drug therapeutically targets RNAdependent RNA polymerase, which is essential for the self-renewal of RNA viruses [4,8] [9]. These preliminary ndings support the use of remdesivir in patients hospitalized due to COVID-19 who require supplemental oxygen therapy.…”

“…All patients in the RDT group received combination treatment with RDT. Remdesivir was administered intravenously as a 200-mg loading dose on day 1, followed by 100 mg from days 2 to 5 (without invasive mechanical ventilation) or 10 (with invasive mechanical ventilation) [8]. Oral or intravenous dexamethasone was administered at a dose of 6 mg daily for up to 10 days [5].…”

The COVID-19 Pandemic Impact on Cardio-Oncology: Results From the COVID-19 International Collaborative Network Survey.

“…The low utilization rate of both remdesivir and tocilizumab re ects the struggle to manage this very sick population given the lack of established and available treatments. Recent promising new data on the use of remdesivir on patients with severe COVID-19 infection (44,45), may increase its use and availability.…”