Effect of Remdesivir vs Standard Care on Clinical Status at 11 Days in Patients With Moderate COVID-19

Abstract

IMPORTANCE Remdesivir demonstrated clinical benefit in a placebo-controlled trial in patients with severe coronavirus disease 2019 (COVID-19), but its effect in patients with moderate disease is unknown. OBJECTIVE To determine the efficacy of 5 or 10 days of remdesivir treatment compared with standard care on clinical status on day 11 after initiation of treatment. DESIGN, SETTING, AND PARTICIPANTS Randomized, open-label trial of hospitalized patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and moderate COVID-19 pneumonia (pulmonary infiltrates and room-air oxygen saturation >94%) enrolled from March 15 through April 18, 2020, at 105 hospitals in the United States, Europe, and Asia. The date of final follow-up was May 20, 2020. INTERVENTIONS Patients were randomized in a 1:1:1 ratio to receive 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. MAIN OUTCOMES AND MEASURES The primary end point was clinical status on day 11 on a 7-point ordinal scale ranging from death (category 1) to discharged (category 7). Differences between remdesivir treatment groups and standard care were calculated using proportional odds models and expressed as odds ratios. An odds ratio greater than 1 indicates difference in clinical status distribution toward category 7 for the remdesivir group vs the standard care group. RESULTS Among 596 patients who were randomized, 584 began the study and received remdesivir or continued standard care (median age, 57 [interquartile range, 46-66] years; 227 [39%] women; 56% had cardiovascular disease, 42% hypertension, and 40% diabetes), and 533 (91%) completed the trial. 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, patients in the 5-day remdesivir group had statistically significantly higher odds of a better clinical status distribution than those receiving standard care (odds ratio, 1.65; 95% CI, 1.09-2.48; P = .02). The clinical status distribution on day 11 between the 10-day remdesivir and standard care groups was not significantly different (P = .18 by Wilcoxon rank sum test). By day 28, 9 patients had died: 2 (1%) in the 5-day remdesivir group, 3 (2%) in the 10-day remdesivir group, and 4 (2%) in the standard care group. Nausea (10% vs 3%), hypokalemia (6% vs 2%), and headache (5% vs 3%) were more frequent among remdesivir-treated patients compared with standard care. CONCLUSIONS AND RELEVANCE Among patients with moderate COVID-19, those randomized to a 10-day course of remdesivir did not have a statistically significant difference in clinical status compared with standard care at 11 days after initiation of treatment. Patients randomized to a 5-day course of remdesivir had a statistically significant difference in clinical status compared with standard care, but the difference was of uncertain clinical importance.

The therapeutic effect and safety of the drugs for COVID-19: a systematic review and meta-analysis

“…The screening process was shown in figure 1 and 3860 studies were identified according to the research strategy initially. In total, 22 studies containing 12795 patients were adopted in our study and all of them were published in English 10,12,[21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40] . Among trails included, half of them were RCTs, and the other were Non-RCTs.…”

Clinical effectiveness of drugs in hospitalized patients with COVID-19: a systematic review and meta-analysis

“…One study reported the median time (in days) to reach a NEWS2 score of zero [23] ( Table 2). The study published by Spinner [8] also reported clinical improvement at days 7, 14, and 28, but it is not declared which scale was used to assess the clinical improvement.…”

“…In this review, the data were extracted from nine studies reporting any severe adverse events [8][9][10]18,19,[21][22][23]26] (It must be noted that a patient can develop one or more than one adverse event). Severe (or serious) adverse events were extracted as dichotomous data (Table 2).…”

“…The conclusions reported by seven studies suggest that there is no benefit with the use of lopinavir-ritonavir [19], remdesivir [8,18], hydroxychloroquine [9,26] and chloroquine at high dosages [10]. However, two studies reported that dexamethasone resulted in lower mortality at day 28 among patients with severe clinical conditions [20] and a higher mean number of days alive and free form mechanical ventilation [22]; both studies together make up a total sample of 6724 patients.…”

“…The use of antivirals or other repositioning drugs is essential for clinical improvement and survival. In the absence of a specific treatment, in vitro and in vivo studies have been proposed to use existing drugs such as tocilizumab (monoclonal antibodies) [7], remdesivir (antiviral) [8], chloroquine and hydroxychloroquine (antimalarial) [9,10], lopinavir and ritonavir (antiretrovirals) [11], dexamethasone (glucocorticoid) [12], convalescent plasma (neutralizing antibody) [13], and traditional medicine [14,15]. All of them showed beneficial effects in preclinical studies and some clinical studies; however, evaluating the treatments used in hospitalized patients is required.…”