RCT: Lack of significant effect of Paxlovid (nirmatrelvir–ritonavir) on symptom alleviation in Covid-19

Study Design and Population:

This phase 2–3 randomized clinical trial investigated the efficacy of nirmatrelvir in combination with ritonavir for treating mild-to-moderate Covid-19 in adults. Participants, both vaccinated and unvaccinated, were enrolled based on their risk factors for severe Covid-19. The study included 1296 adults who had confirmed Covid-19 with symptom onset within the past 5 days. They were randomly assigned to receive either nirmatrelvir–ritonavir or placebo every 12 hours for 5 days.

Main Findings:

The primary endpoint was the time to sustained alleviation of all targeted Covid-19 signs and symptoms. Results showed that the median time to alleviation was 12 days for the treatment group and 13 days for the placebo group, a difference that was not statistically significant (P=0.60). Hospitalizations and deaths were slightly lower in the treatment group (0.8%) compared to the placebo group (1.6%), but this difference was also not statistically significant. Adverse events were similar across both groups, with dysgeusia and diarrhea being the most common in the treatment group.

Implications for Practice:

The findings indicate that nirmatrelvir–ritonavir treatment does not significantly reduce the time to symptom alleviation for Covid-19 compared to placebo among vaccinated or unvaccinated adults. These results suggest that further research is needed to explore the potential benefits of this treatment in specific subpopulations or in combination with other interventions.

Reference (free full-text):

Reference: Hammond J. et al. (2024). Nirmatrelvir for Vaccinated or Unvaccinated Adult Outpatients with Covid-19. N Engl J Med, 390(13), 1186-1195. DOI: 10.1056/NEJMoa2309003