ABSTRACT
Background: Remdesivir (RDV), a direct-acting nucleotide pro-drug inhibitor of viral RNA-dependent RNA polymerases, was approved by the FDA for the treatment of hospitalized patients (pts) with COVID-19 infection and has been shown to shorten time to recovery and improve clinical outcomes in randomized clinical trials. We present the final Day 28 (D28) analysis of RDV vs standard of care (SOC) (interim Day 14 [D14] analysis published [Olender et al. Clin Infect Dis 2020]). Methods: Final comparative analysis from two studies: a prospective phase 3, randomized study of RDV (RDV cohort) and a real-world retrospective cohort study of SOC (non-RDV cohort). Both studies enrolled pts with SARS-CoV-2 infection confirmed by polymerase chain reaction, who had oxygen saturation ≤94% on room air or required supplemental oxygen and had pulmonary infiltrates. Pts in the RDV cohort were randomized 1:1 to receive IV RDV for 5 or 10 days (200 mg on Day 1 followed by 100 mg/day on Days 2-5 or 2-10), plus SOC;the two randomized dose-groups were combined for analysis. Pts in the non-RDV cohort received SOC as determined by local treatment practices (excluding RDV). Analysis populations were balanced using propensity score (PS) matching. The coprimary endpoints were D14 clinical recovery (determined using a 7-point ordinal scale) and D28 all-cause mortality. Factors associated with D28 mortality were assessed using a multivariable logistic regression model. Results: After PS matching, baseline characteristics were generally similar in the RDV and non-RDV cohorts;median age 61 years, 63% male, 42% obese, 12% Black, 71% no/low-flow oxygen use, 25% high-flow oxygen, 3% ventilated. Pts in the RDV cohort had significantly higher D14 clinical recovery rates (65% vs 57%) and significantly lower D28 mortality rates (12% vs 16%) compared with the non-RDV cohort (Table). In the multivariable analysis, in addition to RDV use, a lower risk of death at D28 was associated with: younger age;being female;being White (versus being Black/African American);receiving an HIV protease inhibitor prior to baseline;not having cardiovascular disease or COPD;more days of symptoms prior to baseline;and being on room air or low-flow oxygen at baseline (versus being on invasive mechanical ventilation). Conclusion: RDV was associated with significantly higher rates of clinical recovery at Day 14 and lower Day 28 mortality compared with SOC in hospitalized pts with severe SARS-CoV-2 infection.
ABSTRACT
Background: Clinical practice patterns for hospitalized COVID-19 patients have rapidly evolved, including specific treatment utilization. In turn, outcomes including time to improvement and mortality have also changed, but some reports have shown disproportionate mortality in Blacks. Data on the use of COVID-19 treatments over time and temporal association with hospital mortality and length of stay (LOS), along with assessments by race, are lacking. Methods: This was a retrospective cohort study of adult patients with a discharge diagnosis of COVID-19 (ICD-10-CM: U07.1) admitted between May-Nov 2020 using the chargemaster inpatient data from the Premier Healthcare Database. Demographic characteristics of the cohort were summarized. Utilization of remdesivir (RDV), dexamethasone, anticoagulants, tocilizumab, sarilumab and baricitinib were examined. Median hospital and intensive care unit (ICU) LOS were assessed over time. In-hospital mortality was identified through discharge status. Unadjusted mortality rates over time are reported. Results: Between May-Nov 2020, 190,529 patients were hospitalized for COVID-19 in 823 US hospitals. Patients had a mean age of 64 years, 64% were White, 19% Black, 53% male and 65% had Medicare/ Medicaid as primary payor. Black patients were younger than White (mean 60 vs. 66 years). Significant comorbidities (>20%) were similar between overall cohort and Black patients and included chronic pulmonary disease, hypertension and obesity. From May to Nov, overall RDV utilization increased from 5% to 47%, dexamethasone utilization increased from 7% to 77% and anticoagulant treatment utilization decreased from 32% to 24% (Figure). Few patients received tocilizumab (5%), sarilumab (0.02%) and baricitinib (0.003%). Among Black patients, RDV use increased from 5% to 39% and dexamethasone use increased from 6% to 74%. The median LOS of the overall cohort and Black cohort decreased from 6 days in May to 5 days in Nov, and overall ICU LOS for patients decreased from 5 to 4 days during this time;5 to 3 in Black patients. Overall in-hospital mortality rate decreased by 35%, and by 38% in Black patients. Conclusion:In US hospitalized patients, use of both dexamethasone and RDV has increased approximately 10-fold from May to Nov. Over this same time, a 35% reduction in mortality, a 17% reduction in LOS and 20% reduction in ICU stay were observed. Besides age, no notable differences were apparent by race. Understanding the drivers of improvement in outcomes requires further analyses.