Alleviation of COVID-19 Symptoms and Reduction in Healthcare Utilization Among High-Risk Patients Treated With Nirmatrelvir/Ritonavir (NMV/R): A phase 3 randomized trial
PhD Jennifer Hammond, BSN Heidi Leister-Tebbe, MPH, MSPT Annie Gardner, PhD Paula Abreu, PhD Weihang Bao, MA Wayne Wisemandle, MPH Wajeeha Ansari, PhD Magdalena Alicja Harrington, MD Abraham Simón-Campos, MD Kara W Chew, MD Rienk Pypstra, MD, PhD James M Rusnak
Clinical Infectious Diseases, doi:10.1093/cid/ciae551
Methods: This phase 2/3, double-blind, randomized (1:1) study assessed oral NMV/r 300 mg/100 mg versus placebo every 12 hours for 5 days in high-risk, unvaccinated, nonhospitalized, symptomatic adults with COVID-19 from 343 sites across 21 countries. In testing the primary endpoint of COVID-19-related hospitalization and all-cause deaths and key secondary endpoints including symptom duration and COVID-19-related medical visits, Type I error was controlled with prespecified sequential testing and the Hochberg procedure. Results: Among 2113 randomized patients enrolled from July 2021 through December 2021, 1966 (NMV/r, n=977; placebo, n=989) were included in the prespecified analysis population (symptom onset ≤5 days, did not receive monoclonal antibodies). NMV/r significantly reduced times to sustained alleviation (median, 13 vs 15 days; hazard ratio [HR]=1.27, p<0.0001) and resolution (16 vs 19 days; HR=1.20, p=0.0022) through Day 28 and significantly reduced the number of COVID-19-related medical visits and the proportion of patients with such visits. Hospitalized patients treated with NMV/r had shorter stays, none required ICU admission or mechanical ventilation, and all were discharged to home/self-care. Fewer NMV/r-treated patients required additional treatment for COVID-19. No NMV/r-treated patients died through Week 24 compared with 15 placebo-treated patients.
Conclusions: In addition to reducing COVID-19-related hospitalization or death from any cause through Day 28, NMV/r was found to also reduce duration of COVID-19 symptoms and utilization of healthcare resources versus placebo in patients at high risk of progressing to severe disease.
Author Contributions: JH and HLT were involved in study design, data analysis, and data verification. AG, WA, KWC, RP, and JMR were involved in study design and data analysis. PA, WB, and WW were involved in study design, data analysis, data verification, and statistical analysis. MAH was involved in study design. ASC was involved in data analysis. All authors had access to the data and contributed to the writing of the manuscript.
Conflicts of Interests
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'abstract': '<jats:title>Abstract</jats:title>\n'
' <jats:sec>\n'
' <jats:title>Background</jats:title>\n'
' <jats:p>Nirmatrelvir/ritonavir (NMV/r) is an oral antiviral treatment for '
'mild to moderate COVID-19.</jats:p>\n'
' </jats:sec>\n'
' <jats:sec>\n'
' <jats:title>Methods</jats:title>\n'
' <jats:p>This phase 2/3, double-blind, randomized (1:1) study assessed oral '
'NMV/r 300 mg/100 mg versus placebo every 12 hours for 5 days in high-risk, unvaccinated, '
'nonhospitalized, symptomatic adults with COVID-19 from 343 sites across 21 countries. In '
'testing the primary endpoint of COVID-19‒related hospitalization and all-cause deaths and key '
'secondary endpoints including symptom duration and COVID-19‒related medical visits, Type I '
'error was controlled with prespecified sequential testing and the Hochberg '
'procedure.</jats:p>\n'
' </jats:sec>\n'
' <jats:sec>\n'
' <jats:title>Results</jats:title>\n'
' <jats:p>Among 2113 randomized patients enrolled from July 2021 through '
'December 2021, 1966 (NMV/r, n=977; placebo, n=989) were included in the prespecified analysis '
'population (symptom onset ≤5 days, did not receive monoclonal antibodies). NMV/r '
'significantly reduced times to sustained alleviation (median, 13 vs 15 days; hazard ratio '
'[HR]=1.27, p&lt;0.0001) and resolution (16 vs 19 days; HR=1.20, p=0.0022) through Day 28 '
'and significantly reduced the number of COVID-19‒related medical visits and the proportion of '
'patients with such visits. Hospitalized patients treated with NMV/r had shorter stays, none '
'required ICU admission or mechanical ventilation, and all were discharged to home/self-care. '
'Fewer NMV/r-treated patients required additional treatment for COVID-19. No NMV/r-treated '
'patients died through Week 24 compared with 15 placebo-treated patients.</jats:p>\n'
' </jats:sec>\n'
' <jats:sec>\n'
' <jats:title>Conclusions</jats:title>\n'
' <jats:p>In addition to reducing COVID-19‒related hospitalization or death '
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'and utilization of healthcare resources versus placebo in patients at high risk of '
'progressing to severe disease.</jats:p>\n'
' </jats:sec>\n'
' <jats:sec>\n'
' <jats:title>Clinical Trial Information</jats:title>\n'
' <jats:p>ClinicalTrials.gov, NCT04960202, '
'https://clinicaltrials.gov/study/NCT04960202</jats:p>\n'
' </jats:sec>',
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