Investigational medications in 9,638 hospitalized patients with severe COVID-19: lessons from the "fail-and-learn" strategy during the first two waves of the pandemic in 2020

• Published in: Patient safety in surgery 2023-04, Vol.17 (1), p.7-7, Article 7
• Main Authors: Delgado, Adam C, Cornett, Brendon, Choi, Ye Ji, Colosimo, Christina, Stahel, Vincent P, Dziadkowiec, Oliwier, Stahel, Philip F
• Format: Article
• Language: English
• Subjects: Analysis; Antibiotics; Antiviral drugs; Autoimmune diseases; Azithromycin; Body weight; Clinical trials; Comorbidity; Coronaviruses; Corticoids; Corticosteroids; COVID-19; COVID-19 vaccines; Disease transmission; Drugs; Effectiveness; Epidemics; Evidence-based medicine; FDA approval; Health care policy; Health services; Homeopathy; Hospital patients; Hydroxychloroquine; Independent regulatory commissions; Materia medica and therapeutics; Mechanical ventilation; Medical research; Medicine, Experimental; Minority & ethnic groups; Monoclonal antibodies; Mortality; National health insurance; Ostomy; Oxygen; Pandemics; Patients; Ratios; Regression analysis; Remdesivir; Respiratory distress syndrome; Severe acute respiratory syndrome coronavirus 2; Statistical analysis; Steroids; Surges; Therapeutics; Tocilizumab; Vaccines; Ventilation; Ventilators; Viral diseases; Viral infections; Windows (intervals)
• ISSN: 1754-9493; 1754-9493
• DOI: 10.1186/s13037-023-00358-9

The early surge of the novel coronavirus disease 2019 (COVID-19) pandemic introduced a significant clinical challenge due to the high case-fatality rate in absence of evidence-based recommendations. The empirical treatment modalities were relegated to historical expertise from the traditional management of acute respiratory distress syndrome (ARDS) in conjunction with off-label pharmaceutical agents endorsed under the "emergency use authorization" (EUA) paradigm by regulatory agencies. This study was designed to evaluate the insights from the "fail-and-learn" strategy in 2020 before the availability of COVID-19 vaccines and access to reliable insights from high-quality randomized controlled trials. A retrospective, multicenter, propensity-matched, case-control study was performed on a data registry comprising 186 hospitals from a national health care system in the United States, designed to investigate the efficacy of empirical treatment modalities during the early surge of the COVID-19 pandemic in 2020. Reflective of the time-windows of the initial two surges of the pandemic in 2020, patients were stratified into "Early 2020" (March 1-June 30) versus "Late 2020" (July 1-December 31) study cohorts. Logistic regression was applied to determine the efficacy of prevalent medications (remdesivir, azithromycin, hydroxychloroquine, corticosteroids, tocilizumab) and supplemental oxygen delivery modalities (invasive vs. non-invasive ventilation) on patient outcomes. The primary outcome measure was in-hospital mortality. Group comparisons were adjusted for covariates related to age, gender, ethnicity, body weight, comorbidities, and treatment modalities pertinent to organ failure replacement. From a total of 87,788 patients in the multicenter data registry screened in this study, 9,638 patients were included who received 19,763 COVID-19 medications during the first two waves of the 2020 pandemic. The results showed a minimal, yet statistically significant, association with hydroxychloroquine in "Early 2020" and remdesivir in "Late 2020" with reduced odds of mortality (odds ratios 0.72 and 0.76, respectively; P = 0.01). Azithromycin was the only medication associated with decreased odds of mortality during both study time-windows (odds ratios 0.79 and 0.68, respectively; P