Acute respiratory distress syndrome coronavirus 2 (SARS-CoV-2) was identified in December 2019 as the cause of respiratory illness, COVID-19. Although several therapeutic drugs have been evaluated for the treatment of COVID-19, few have been efficacious. Remdesivir (GS-5734), inhibits SARS-CoV-2 in vitro, and reduces lung virus levels and lung damage. However, the clinical efficacy and safety of remdesivir in COVID-19 patients needs to be explored.
This study assessed the clinical efficacy and safety of intravenous remdesivir in patients hospitalized with laboratory-confirmed COVID-19. The preliminary results of the first stage of the Adaptive Covid-19 Treatment Trial (ACTT-1) are presented here.
- Multicenter, randomized, placebo-controlled, double-blind trial
- Enrollment for ACTT-1 began on February 21, 2020, and ended on April 19, 2020.
- Patients hospitalized with COVID-19 with evidence of lower respiratory tract involvement were randomized to intravenous remdesivir (200 mg loading dose on day 1 followed by 100 mg daily for upto 9 additional days) or placebo for 10 days
- The cohort underwent clinical assessment daily from day 1 through day 29
- Time to recovery, defined as the first day during the 28 days from enrollment, on which a patient satisfied categories 1, 2, or 3 on the eight-category ordinal scale.
- Mortality rate at day 14 and 28
- Incidence of grade 3 and 4 adverse events and serious adverse events
- Of the 1107 patients who were evaluated for eligibility, 1063 patients underwent randomization.
- Early unblinding of the results was recommended on the basis of findings from an analysis that showed shortened time to recovery in the remdesivir group by the data and safety monitoring board.
- The analysis population included 1059 patients; out of which 538 received remdesivir and 521received placebo
- Baseline characteristics were as follows
- The mean age of patients was 58.9 years, and 64.3% were male
- 27% and 52.1% had either one or two or more of the prespecified coexisting conditions at enrollment, most commonly hypertension (49.6%), obesity (37.0%), and type 2 diabetes mellitus (29.7%)
- The median number of days between symptom onset and randomization was 9
- 88.7% had severe disease at enrollment
- The remdesivir group had a shorter median recovery time of 11 days as compared to 15 days in the placebo group (rate ratio for recovery, 1.32; p<0.001)
- The Kaplan-Meier estimates of mortality by 14 days were lower in the patients receiving remdesivir (hazard ratio for death, 0.70) as shown in figure 1.
- The incidence of serious adverse events was also lower in the study group as shown in figure 1.
- Acute respiratory failure, hypotension, viral pneumonia, and acute kidney injury were slightly more common among patients in the placebo group
- The most common adverse events in the remdesivir group were anemia or decreased hemoglobin, acute kidney injury, decreased estimated glomerular filtration rate or creatinine clearance, or increased blood creatinine, hyperglycemia and increased aminotransferase levels
- Remdesivir was superior to placebo in shortening the time to recovery in adults hospitalized with Covid-19.
- The benefit was most apparent in patients with a baseline ordinal score of 5 (requiring oxygen).
- The COVID-19 cases need to be identified and the antiviral treatment should be initiated before the pulmonary disease progresses to the need for mechanical ventilation.
N Engl J Med. 2020. Doi: 10.1056/NEJMoa2007764.