According to data from an open-label Phase III study published in the Journal of the American Medical Association, patients with moderate coronavirus disease 2019 (COVID-19) pneumonia randomized to receive remdesivir treatment for up to 5 days had significantly higher odds of achieving clinical improvement at the 11-day mark than those receiving standard care.
However, the authors led by Christoph D. Spinner, MD, Technical University of Munich, School of Medicine, University Hospital Rechts der Isar, Munich, Germany, cautioned that the effect size was “of uncertain clinical importance.” Meanwhile, patients randomized to a 10-day course of remdesivir did not have a statistically significant difference in clinical status compared to standard care at 11 days.
The study included nearly 600 hospitalized patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and moderate COVID-19 pneumonia, with confirmed infiltrates by radiology, but with room-air oxygen saturations greater than 94% at rest. Participants were enrolled from March 15 through April 18, 2020, at 105 hospitals in the US, Europe and Asia. Median age was 57 years [interquartile range, 46-66]; 227 [39%] were women; 56% had cardiovascular disease, 42% hypertension, and 40% diabetes, and 533 (91%) completed the trial.
Patients were randomly assigned a 10-day course of remdesivir (n = 197), a 5-day course of remdesivir (n = 199), or standard care (n = 200). Remdesivir was dosed intravenously at 200 mg on day 1 followed by 100 mg/d. The primary endpoint was clinical status on day 11 on a 7-point ordinal scale ranging from death (category 1) to discharged (category 7).
The median length of treatment was 5 days for patients in the 5-day remdesivir group and 6 days for patients in the 10-day remdesivir group. On day 11, the odds ratio for patients in the 5-day group having a better clinical status distribution on the 7-point scale was 1.65 versus standard care (95% CI, 1.09-2.48; P = .02). There was no statistically significant difference between the 10-day treatment arm and standard care (P = .18). There were also no significant differences between the remdesivir and standard care groups in duration of oxygen therapy or hospitalization.
By day 14, the clinical status of the 5- and 10-day remdesivir groups was significantly different than that of the standard care group (P = .03 for both groups). Clinical status remained significantly different by day 28 in the 10-day group (P = .03) compared with standard care.
Adverse events that were more common in remdesivir-treated patients were nausea, hypokalemia and headache. Serious adverse events were less common in the remdesivir groups (5% in both) than in standard care (9%). All 9 deaths through day 28 (2 [1%] in the 5-day remdesivir group, 3 [2%] in the 10-day remdesivir group, and 4 [2%] in the standard care group) occurred in patients aged 64 years or older, and none was attributed to remdesivir treatment.
“Several factors may account for the lack of difference in clinical status observed in the 10-day remdesivir group, although the median length of treatment was 6 days in this group. Given the open-label design of the study and the requirement for intravenous dosing of remdesivir, discharge decisions may have been influenced by the assigned duration of remdesivir therapy. Rates of discharge peaked on the day after the end of dosing in both groups: on day 6 for the 5-day group and on day 11 for the 10-day group,” the authors said. However, they noted that when outcomes at days 14 and 28 were evaluated, similar distributions of clinical status were observed between patients in the remdesivir groups, “possibly pointing to differences compared with standard care.”
The authors also said there was a possibility that the extra days of hospitalization and remdesivir treatment for patients in the 10-day group might have potentially contributed to negative outcomes, although they pointed out that rates of grade 3 or higher adverse events and serious adverse events were not worse in the 10-day group than in the 5-day and standard care arms.
The researchers suggested “future trials should consider studying individual severity strata incorporating further clarification and refinements in their definitions.” They added that “factors that contribute to patients progressing to severe and critical COVID-19 remain to be elucidated,” but that the risk of rapid disease progression described to date “points to the potential benefit of earlier intervention with an effective antiviral.”