BACKGROUND AND PURPOSE:

• Paxlovid (nirmatrelvir with ritonavir) is an effective antiviral treatment for unvaccinated adults with COVID-19 at risk for severe disease
• Effectiveness in other groups remain unclear
• Hammond et al. (NEJM, 2024) evaluated the efficacy and safety of nirmatrelvir–ritonavir among vaccinated adults at risk for severe COVID-19 as well as unvaccinated individuals at standard risk

METHODS:

• Phase 2 to 3 double-blind, randomized, placebo-controlled trial
• Participants
  • Adults with confirmed COVID-19 with symptom onset within the past 5 days who were
    • ≥1 risk factor severe disease: Fully vaccinated against COVID-19 or
    • 0 risk factors for severe disease: Never vaccinated or not vaccinated within the previous year
• Interventions
  • Nirmatrelvir–ritonavir every 12 hours for 5 days
  • Placebo
• Study design
  • Participants logged the presence and severity of prespecified COVID-19 signs and symptoms daily from day 1 through day 28
• Primary outcome
  • Time to sustained alleviation of all targeted COVID-19 signs and symptoms
• Secondary outcome
  • COVID-19–related hospitalization and death from any cause through day 28

RESULTS:

• Nirmatrelvir–ritonavir: 654 participants | Placebo: 634 participants
• There was no significant difference in median time to sustained alleviation of all targeted signs and symptoms of COVID-19
  • Nirmatrelvir–ritonavir: 12 days | Placebo: 13 days | P=0.60
• Hospitalizations for COVID-19 or death from any cause
  • Nirmatrelvir–ritonavir: 0.8% | Placebo: 1.6%
  • Difference −0.8 percentage points (95% CI, −2.0 to 0.4)
• The percentages of participants with adverse events were similar in the two groups
  • Nirmatrelvir–ritonavir: 25.8% | Placebo: 24.1%
• In the nirmatrelvir–ritonavir group, the most commonly reported treatment-related adverse events were
  • Dysgeusia: 5.8%
  • Diarrhea: 2.1%

CONCLUSION:

• Paxlovid did not alter the time to sustained symptom alleviation in adult participants with Covid-19 who were at standard or high risk for severe disease
• The authors state

Nirmatrelvir–ritonavir was not associated with a significantly shorter time to sustained alleviation of Covid-19 symptoms than placebo, and the usefulness of nirmatrelvir–ritonavir in patients who are not at high risk for severe Covid-19 has not been established

Learn More – Primary Sources:

Nirmatrelvir for Vaccinated or Unvaccinated Adult Outpatients with Covid-19