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

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.

Goldman, Jason D., David C. B. Lye, David S. Hui, Kristen M. Marks, Raffaele Bruno, Rocio Montejano, Christoph D. Spinner, Massimo Galli, Mi-Young Ahn, Ronald G. Nahass, Yao-Shen Chen, Devi SenGupta, Robert H. Hyland, Anu O. Osinusi, Huyen Cao, Christiana Blair, Xuelian Wei, Anuj Gaggar, Diana M. Brainard, William J. Towner, Jose Muñoz, Kathleen M. Mullane, Francisco M. Marty, Karen T. Tashima, George Diaz, and Aruna Subramanian.

2020-11-05

Goldman, Jason D., David C. B. Lye, David S. Hui, Kristen M. Marks, Raffaele Bruno, Rocio Montejano, Christoph D. Spinner, Massimo Galli, Mi-Young Ahn, Ronald G. Nahass, Yao-Shen Chen, Devi SenGupta, Robert H. Hyland, Anu O. Osinusi, Huyen Cao, Christiana Blair, Xuelian Wei, Anuj Gaggar, Diana M. Brainard, William J. Towner, Jose Muñoz, Kathleen M. Mullane, Francisco M. Marty, Karen T. Tashima, George Diaz, and Aruna Subramanian. 2020. "Remdesivir for 5 or 10 Days in Patients with Severe Covid-19." New England Journal of Medicine 383 (19):1827-37.

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. opens in new tab.)

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