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Evaluating Primary Endpoints for COVID-19 Therapeutic Trials to Assess Recovery

Douin, David J; Siegel, Lianne; Grandits, Greg; Phillips, Andrew; Aggarwal, Neil R; Baker, Jason; Brown, Samuel M; ... ACTIV-3/Therapeutics for Inpatients with COVID-19 (TICO) Study G; + view all (2022) Evaluating Primary Endpoints for COVID-19 Therapeutic Trials to Assess Recovery. American Journal of Respiratory and Critical Care Medicine , 206 (6) pp. 730-739. 10.1164/rccm.202112-2836OC. Green open access

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Abstract

RATIONALE: Uncertainty regarding the natural history of coronavirus disease 2019 (COVID-19) led to difficulty in efficacy endpoint selection for therapeutic trials. Capturing outcomes that occur after hospital discharge may improve assessment of clinical recovery among hospitalized COVID-19 patients. OBJECTIVES: Evaluate 90-day clinical course of patients hospitalized with COVID-19 comparing three distinct definitions of recovery. METHODS: We used pooled data from three clinical trials of neutralizing monoclonal antibodies to compare: 1) the hospital discharge approach 2) the Therapeutics for Inpatients with COVID-19 (TICO) trials "sustained recovery" approach, and 3) a comprehensive approach. At the time of enrollment, all patients were hospitalized in a non-intensive care unit setting without organ failure or major extrapulmonary manifestations of COVID-19. We defined discordance as a difference between time to recovery. MEASUREMENTS AND MAIN RESULTS: Discordance between the hospital discharge and comprehensive approaches occurred in 170 (20%) of 850 enrolled participants, including 126 hospital readmissions and 24 deaths after initial hospital discharge. Discordant participants were older (median age 68 vs. 59 years; p<0.001) and more had a comorbidity (84% vs. 70%; p<0.001). Of 170 discordant participants, 106 (62%) had post-discharge events captured by the TICO approach. CONCLUSIONS: Among patients hospitalized with COVID-19, 20% had clinically significant post-discharge events within 90 days after randomization, in patients that would be considered "recovered" using the hospital discharge approach. Employing the TICO approach balances length of follow-up with practical limitations. However, clinical trials of COVID-19 therapeutics should employ follow-up times up to 90 days to assess clinical recovery more accurately.

Type: Article
Title: Evaluating Primary Endpoints for COVID-19 Therapeutic Trials to Assess Recovery
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1164/rccm.202112-2836OC
Publisher version: https://doi.org/10.1164/rccm.202112-2836OC
Language: English
Additional information: This article is open access and distributed under the terms of the Creative Commons Attribution NonCommercial No Derivatives License 4.0 (https://creativecommons.org/licenses/by-nc-nd/4.0/). For commercial usage and reprints please contact Diane Gern (dgern@thoracic.org).
Keywords: COVID-19, Monoclonal Antibodies, Outcomes Assessment
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute for Global Health > Infection and Population Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute for Global Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology > MRC Clinical Trials Unit at UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology
URI: https://discovery.ucl.ac.uk/id/eprint/10149589
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