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Goldman JD, Lye DCB, Hui DS, et al. Remdesivir for 5 or 10 Days in Patients with Severe Covid-19. N Engl J Med. 2020 May 27. doi: 10.1056/NEJMoa2015301. (Original study)
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.).


Related DynaMed Topics

Ratings
Discipline Area Score
Family Medicine (FM)/General Practice (GP) 7 / 7
General Internal Medicine-Primary Care(US) 7 / 7
Intensivist/Critical Care 6 / 7
Public Health 6 / 7
Hospital Doctor/Hospitalists 6 / 7
Internal Medicine 6 / 7
Infectious Disease 6 / 7
Comments from MORE raters

Hospital Doctor/Hospitalists rater

The data are not very good, but at least it`s something. A 5-day course in non-critically ill patients seems to be the way to go at this time until new data or new pharmaceuticals show better options.

Infectious Disease rater

This paper looks at two different regimens of remdesivir for COVID infection. The 5-day and 10-day courses are comparably effective and toxic. This is not entirely surprising. Since there is no control group, it does not give further information on the potential benefits compared with "no therapy." We are still sorting out the ideal time to deploy remdesivir therapy, and this study will allow us to use the shorter course and reserve supplies at a time when they are limited. In that sense, it is good news that additional days of treatment do not seem to provide further benefit.

Infectious Disease rater

Unfortunately, without a placebo group, this study adds little to our knowledge base about possible treatments for COVID-19 infection.

Infectious Disease rater

This study provides evidence that 5- and 10-day courses of remdesivir are equally effective in patients with Covid-19 infection. This is useful information if ever remdesivir needs to be rationed. An important finding is that patients needing mechanical ventilation on day 5 seem to benefit if remdesivir is continued beyond 5 days. A limitation of the study is that it did not include patients intubated at baseline. Beigel et al (DOI: 10.1056/NEJMoa2007764) compared remdesivir with placebo, but in that study approximately 25% of patients were receiving mechanical ventilation or ECMO at baseline (Supplementary appendix). Thus, it cannot be used for any comparisons. Finally, one must note that only approximately 40% of patients in the 10-day group actually received 10 days of treatment.

Intensivist/Critical Care rater

The other NEJM remdesivir article is much more important (with a placebo comparison). This one examining duration was smaller and showed no difference. Not sure we are confident we should be using remdesivir period, which is a more important question than duration if we do use it.

Intensivist/Critical Care rater

Good-sized international phase 3 trial compared 5 days of remdesivir with 10 days in patients with Covid-19 infection. There was no apparent difference in outcome between the two treatment lengths. This provides some guidance for centers that apply for remdesivir, but the real question is efficacy of the drug in real-life settings. This study does not answer that question.

Internal Medicine rater

Somewhat useful in the context of the placebo-controlled trial, but a small n, baseline differences, etc, impair the amount of weight I would give it.
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