ABSTRACT
Background: Remdesivir (RDV) has been shown to shorten recovery time and was well tolerated in patients with severe COVID-19. Here we report baseline characteristics associated with clinical improvement at day (d) 14. Methods: We enrolled hospitalized patients with confirmed SARS-CoV-2 infection, oxygen saturation >94% on room air, and radiological evidence of pneumonia. Patients were randomized 1:1:1 to receive 5d or 10d of intravenous RDV once daily plus standard of care (SoC), or SoC only. For this analysis, patients were followed through discharge, d14, or death. Baseline demographic and disease characteristics associated with clinical improvement in oxygen support (≥2-point improvement on a 7-category ordinal scale ranging from discharge to death) were evaluated using multivariable logistic regression methods. Results: 584 patients were randomized and treated (5/10d RDV, n=384;SoC: n=200). 159 (27%) were ≥65y, 227 (39%) female, 328 (61%) white, 102 (19%) Asian, and 99 (19%) Black. 252 participants (43%) were enrolled in Europe, 260 (45%) North America (NA), and 72 (12%) in Asia. Most patients (483 [83%]) were not on supplemental oxygen but required medical care at baseline. In a multivariable model, 5/10d RDV was significantly positively associated with clinical improvement (adjusted odds ratio [OR] 1.69, 95% CI: 1.08, 2.65;p=0.0226). Significant covariables positively associated with clinical improvement included age < 65y (p< 0.0001) and region of treatment (Europe and NA vs Asia, p< 0.0001 each;Table);other examined factors were not significantly associated with clinical improvement, including gender, race, ethnicity, baseline oxygen support, duration of symptoms and hospitalization, obesity, and baseline transaminase levels. Conclusion: In moderate COVID-19 patients, after adjusting for treatment arm, age < 65y and region (NA vs Asia;Europe vs Asia) were associated with higher rates of clinical improvement. These observations recapitulate younger age as positive prognostic factor, and highlight the differences in the impact of the pandemic globally.
ABSTRACT
Background: Remdesivir (RDV), a nucleotide analogue prodrug that inhibits viral RNA polymerases, has demonstrated potent in vitro and in vivo activity against SAR-CoV-2 and favorable clinical efficacy and tolerability in patients with moderate and severe COVID-19 Elevated transaminase levels are commonly seen in patients with severe COVID-19 prior to treatment Here we report safety and clinical outcomes after RDV treatment in patients with normal versus elevated baseline alanine aminotransferase (ALT) levels Methods: We conducted a randomized, open-label, phase 3 trial, involving hospitalized patients with confirmed COVID-19 pneumonia with Sat<94% Patients with screening ALT or AST> 5x the upper limit of normal (ULN) were excluded from the study Patients were randomized 1:1 to receive either 5 or 10 days of intravenous RDV once daily We compared patients with baseline ALT below and above the ULN based on AASLD criteria (ALT 35 U/L for males and 25 U/L for females) Covariates for adjustment included age, sex, race and baseline oxygen support Clinical recovery and all-cause mortality were evaluated using logistic regression Clinical outcomes and adverse events (AEs) were assessed through day 28 Results: Of 397 patients treated with RDV, 215 (54%) had elevated baseline ALT Median ALT was 53 U/L (IQR: 40 - 78 U/L) in the high ALT group Patients with high ALT at time of RDV initiation were younger (median 58 vs 65 years, p<0 001), required less oxygen (p=0 02), and had longer symptom duration (median 10 vs 8 days, p<0.001) prior to first dose of RDV. Incidence of serious AEs, grade ≥3 AEs, and AE leading to discontinuation were similar between groups (Table1). Grade ≥3 hepatobiliary adverse events, particularly transaminase elevations, were not common but numerically higher in the high ALT group (8 8% vs 3 3%, p=0 068) Time to clinical recovery, 2-point clinical improvement, 1-point clinical improvement, room air, and death were similar between groups Conclusion: In severe COVID-19 patients, adverse events and clinical outcomes after RDV initiation were similar among patients with baseline normal ALT and those with elevated ALT (1-5x ULN)(Table Presented).