EPIC-HR
Trial question
What is the role of nirmatrelvir/ritonavir in patients with mild-to-moderate COVID-19 infection at increased risk of progression to severe disease?
Study design
Multi-center
Double blinded
RCT
Population
Characteristics of study participants
50.0% female
50.0% male
N = 1966
1966 patients (976 female, 990 male).
Inclusion criteria: nonhospitalized adult patients with mild-to-moderate COVID-19 infection at increased risk of progression to severe disease.
Key exclusion criteria: history of or need for hospitalization for the treatment of COVID-19 infection; active liver disease; moderate-to-severe renal impairment; HIV infection; active systemic infection other than COVID-19; hypersensitivity or other contraindication to any of the components of the study intervention.
Interventions
N=977 nirmatrelvir/ritonavir (oral dose of 300/100 mg BID for 5 days).
N=989 placebo (matching placebo BID for 5 days).
Primary outcome
Rate of COVID-19-related hospitalization or death from any cause through day 28, treated ≤ 3 days after onset of symptoms
0.74%
6.8%
6.8 %
5.1 %
3.4 %
1.7 %
0.0 %
Nirmatrelvir/ritonavir
Placebo
Significant
decrease ▼
NNT = 16
Significant decrease in the rate of COVID-19-related hospitalization or death from any cause through day 28, treated ≤ 3 days after onset of symptoms (0.74% vs. 6.8%; ARD -6.14, 95% CI -8.21 to -4.07).
Secondary outcomes
Significant decrease in the rate of COVID-19-related hospitalization or death from any cause through day 28, treated ≤ 5 days after onset of symptoms (0.92% vs. 6.47%; ARD -5.64, 95% CI -7.31 to -3.97).
Significantly shorter median time to sustained alleviation of COVID-19 symptoms through day 28 (13 days vs. 15 days; HR 0.79, 95% CI 0.71 to 0.88).
Significantly shorter median time to sustained resolution of COVID-19 symptoms through day 28 (16 days vs. 19 days; HR 0.83, 95% CI 0.74 to 0.93).
Safety outcomes
No significant difference in adverse events.
Conclusion
In nonhospitalized adult patients with mild-to-moderate COVID-19 infection at increased risk of progression to severe disease, nirmatrelvir/ritonavir was superior to placebo with respect to the rate of COVID-19-related hospitalization or death from any cause through day 28, treated ≤ 3 days after onset of symptoms.
Reference
Jennifer Hammond, Heidi Leister-Tebbe, Annie Gardner et al. 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. Clin Infect Dis. 2025 Feb 24;80(2):323-330.
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