tetano
Editor, Senior Moderator
Am J Respir Crit Care Med
. 2022 May 17.
doi: 10.1164/rccm.202112-2836OC. Online ahead of print.
Evaluating Primary Endpoints for COVID-19 Therapeutic Trials to Assess Recovery
David J Douin[SUP] 1 [/SUP], Lianne Siegel[SUP] 2 [/SUP], Greg Grandits[SUP] 3 [/SUP], Andrew Phillips[SUP] 4 [/SUP], Neil R Aggarwal[SUP] 5 [/SUP], Jason Baker[SUP] 6 [/SUP], Samuel M Brown[SUP] 7 [/SUP], Christina C Chang[SUP] 8 [/SUP], Anna L Goodman[SUP] 9 [/SUP], Birgit Grund[SUP] 10 [/SUP], Elizabeth S Higgs[SUP] 11 [/SUP], Catherine L Hough[SUP] 12 [/SUP], Daniel D Murray[SUP] 13 [/SUP], Roger Paredes[SUP] 14 [/SUP], Mahesh Parmar[SUP] 15 [/SUP], Sarah Pett[SUP] 16 [/SUP], Mark N Polizzotto[SUP] 17 [/SUP], Uriel Sandkovsky[SUP] 18 [/SUP], Wesley H Self[SUP] 19 [/SUP], Barnaby E Young[SUP] 20 [/SUP], Abdel G Babiker[SUP] 15 [/SUP], Victoria J Davey[SUP] 21 [/SUP], Virginia Kan[SUP] 22 [/SUP], Annetine C Gelijns[SUP] 23 [/SUP], Gail Matthews[SUP] 8 [/SUP], B Taylor Thompson[SUP] 24 [/SUP], H Clifford Lane[SUP] 11 [/SUP], James D Neaton[SUP] 2 [/SUP], Jens D Lundgren[SUP] 25 [/SUP], Adit A Ginde[SUP] 26 [/SUP], ACTIV-3/Therapeutics for Inpatients with COVID-19 (TICO) Study Group
Affiliations
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.
Keywords: COVID-19; Monoclonal Antibodies; Outcomes Assessment.
. 2022 May 17.
doi: 10.1164/rccm.202112-2836OC. Online ahead of print.
Evaluating Primary Endpoints for COVID-19 Therapeutic Trials to Assess Recovery
David J Douin[SUP] 1 [/SUP], Lianne Siegel[SUP] 2 [/SUP], Greg Grandits[SUP] 3 [/SUP], Andrew Phillips[SUP] 4 [/SUP], Neil R Aggarwal[SUP] 5 [/SUP], Jason Baker[SUP] 6 [/SUP], Samuel M Brown[SUP] 7 [/SUP], Christina C Chang[SUP] 8 [/SUP], Anna L Goodman[SUP] 9 [/SUP], Birgit Grund[SUP] 10 [/SUP], Elizabeth S Higgs[SUP] 11 [/SUP], Catherine L Hough[SUP] 12 [/SUP], Daniel D Murray[SUP] 13 [/SUP], Roger Paredes[SUP] 14 [/SUP], Mahesh Parmar[SUP] 15 [/SUP], Sarah Pett[SUP] 16 [/SUP], Mark N Polizzotto[SUP] 17 [/SUP], Uriel Sandkovsky[SUP] 18 [/SUP], Wesley H Self[SUP] 19 [/SUP], Barnaby E Young[SUP] 20 [/SUP], Abdel G Babiker[SUP] 15 [/SUP], Victoria J Davey[SUP] 21 [/SUP], Virginia Kan[SUP] 22 [/SUP], Annetine C Gelijns[SUP] 23 [/SUP], Gail Matthews[SUP] 8 [/SUP], B Taylor Thompson[SUP] 24 [/SUP], H Clifford Lane[SUP] 11 [/SUP], James D Neaton[SUP] 2 [/SUP], Jens D Lundgren[SUP] 25 [/SUP], Adit A Ginde[SUP] 26 [/SUP], ACTIV-3/Therapeutics for Inpatients with COVID-19 (TICO) Study Group
Affiliations
- PMID: 35580040
- DOI: 10.1164/rccm.202112-2836OC
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.
Keywords: COVID-19; Monoclonal Antibodies; Outcomes Assessment.