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

Abstract

Rationale: Uncertainty regarding the natural history of coronavirus disease (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 patients with COVID-19. 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 TICO (Therapeutics for Inpatients with COVID-19) trials sustained recovery approach; and 3) a comprehensive approach. At the time of enrollment, all patients were hospitalized in a non-ICU 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 postdischarge events captured by the TICO approach. Conclusions: Among patients hospitalized with COVID-19, 20% had clinically significant postdischarge events within 90 days after randomization in patients who would be considered "recovered" using the hospital discharge approach. Using the TICO approach balances length of follow-up with practical limitations. However, clinical trials of COVID-19 therapeutics should use follow-up times up to 90 days to assess clinical recovery more accurately.

• Authors: David J Douin, Lianne Siegel, Greg Grandits, Andrew Phillips, Neil R Aggarwal, Jason Baker, Samuel M Brown, Christina C Chang, Anna L Goodman, Birgit Grund, Elizabeth S Higgs, Catherine L Hough, Daniel D Murray, Roger Paredes, Mahesh Parmar, Sarah Pett, Mark N Polizzotto, Uriel Sandkovsky, Wesley H Self, Barnaby E Young, Abdel G Babiker, Victoria J Davey, Virginia Kan, Annetine C Gelijns, Gail Matthews, B Taylor Thompson, H Clifford Lane, James D Neaton, Jens D Lundgren, Adit A Ginde
• Journal: American journal of respiratory and critical care medicine (Am J Respir Crit Care Med) Vol. 206 Issue 6 Pg. 730-739 (09 15 2022) ISSN: 1535-4970 [Electronic] United States
• PMID: 35580040 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Antibodies, Monoclonal

Topics

• Aftercare
• Aged
• Antibodies, Monoclonal
• COVID-19
• Humans
• Patient Discharge
• SARS-CoV-2
• Treatment Outcome