The following is the summary of “Temporal Improvements in COVID-19 Outcomes for Hospitalized Adults: A Post Hoc Observational Study of Remdesivir Group Participants in the Adaptive COVID-19 Treatment Trial” published in the December 2022 issue of Internal medicine by Potter, et al.

Quick changes were made to the COVID-19 SOC in 2020 and 2021, however, it is uncertain what effect they will have in the long run. Using ACTT(Adaptive COVID-19 Treatment Trial) data, researchers aim to determine whether or not the rate of recovery and death has increased as SOC has progressed. The ACTT was planned as a set of 3 phase 3 trials evaluating COVID-19 treatments from February 2020 through May 2021. These trials were randomized, double-blind, placebo-controlled. Remdesivir plus SOC was compared to placebo plus SOC in ACTT-1, and it was used as the control group in ACTT-2 and ACTT-3. After controlling for confounding factors with propensity score weighting, this post hoc analysis compared the rates of recovery and mortality between the 2 sequential groups of patients who received remdesivir with SOC. Participants in ACTT-3 and ACTT-4 who were given remdesivir plus dexamethasone plus SOC were subjected to the same analysis. Positive outcomes may be explained by the observed SOC trends. (ACTT-1: NCT04280705, ACTT-2: NCT04401579, ACTT-3: NCT04492475, and ACTT-4: NCT04640168 on ClinicalTrials.gov)

About 94 hospitals across 10 nations (86% from the US). Hospitalized adults with COVID-19 were the participants. Mortality and health at 28 days are the metrics used. Adjusted hazard ratios (HRs) were close to 1 despite better outcomes in ACTT-2 than in ACTT-1 (HR for recovery, 1.04 [95% CI, 0.92 to 1.17]; HR for mortality, 0.90 [CI, 0.56 to 1.40]). In ACTT-2, patients were given less hydroxychloroquine and were less likely to require intubation compared to ACTT-1 (odds ratio, 0.75 [CI, 0.53 to 0.97]). There was an improvement in results from ACTT-2 to ACTT-3 (HR for recovery, 1.43 [CI, 1.24 to 1.64]; HR for mortality, 0.45 [CI, 0.21 to 0.97]). Except for a rise in dexamethasone use (from 11 to 77%), ACTT-2 and ACTT-3 shared comparable patterns in terms of potential explanatory factors (SOC trends, case surges, and variation trends). 

The results of ACTT-3 and ACTT-4 were comparable. There was a generalized decline in antibiotic use throughout time. Confounding factors could not be determined. Improved SOC may account for the difference in outcomes between ACTT-1 and ACTT-2, but not between ACTT-2 and ACTT-3, resulting from the differences in patient mix between the 2 groups. These findings provide evidence for removing nonconcurrent controls from platform trial analysis in dynamic treatment fields.

Source: acpjournals.org/doi/10.7326/M22-2116