The Perfect Enemy | Evolving COVID care may have cut recovery, death in some phases
February 8, 2023

Evolving COVID care may have cut recovery, death in some phases

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Adapting COVID-19 standards of care (SOC) to evolving information about optimal treatments may have shortened recovery and reduced deaths in hospitalized adults during some pandemic phases, according to an observational study today in the Annals of Internal Medicine.

A team led by researchers from the US National Institute of Allergy and Infectious Diseases analyzed data from the Adaptive COVID-19 Treatment Trial (ACTT), a staged, phase 3, randomized, controlled trial that assessed 28-day recovery and mortality from February 2020 to May 2021. The trial was conducted in 94 hospitals in 10 countries, with roughly 500 patients per group and 86% of participants from the United States.

ACTT-1 compared the antiviral remdesivir plus SOC to placebo plus SOC, while remdesivir plus SOC was the control group in ACTT-2 and ACTT-3. In ACTT-3 and ACTT-4, the analysis was repeated for participants who received remdesivir plus the anti-inflammatory dexamethasone plus SOC. ACTT-4 compared remdesivir plus the immune inhibitor baricitinib to remdesivir plus dexamethasone.

Outcomes were marginally improved in ACTT-2 over ACTT-1 (adjusted hazard ratio [aHR] for recovery, 1.04; aHR for death, 0.90). Patients were less likely to be intubated in ACTT-2 than in ACTT-1 (odds ratio, 0.75), and hydroxychloroquine use fell.

Outcomes improved from ACTT-2 to ACTT-3 (aHR for recovery, 1.43; aHR for death, 0.45). Explanations for the differences, including changing case loads, SOC, and SARS-CoV-2 variants, were comparable in ACTT-2 and ACTT-3, except for greater dexamethasone use (11% to 77%). ACTT-3 and ACTT-4 outcomes were similar. Across all stages, antibiotic use decreased.

“Although our unadjusted HR estimates describe differences in outcomes between trial stages, the propensity score-weighted HRs account for changes in patient composition over time and represent a ‘stage effect’ attributed to the SOC received during different stages,” they wrote.

The authors noted that they found no improvements in recovery or mortality from August 2020 to May 2021, perhaps because the SOC didn’t change much during that time. “These findings support the exclusion of nonconcurrent controls when analyzing data from platform trials, particularly for COVID-19 treatments and vaccines,” they concluded.