Group of floating coronaviruses
Image Credits: Unplash
![](https://cdn.sanity.io/images/0vv8moc6/contagion/7d2ec392ec25f64de3dbf1dc55d50ecc21a97e25-612x278.jpg?fit=crop&auto=format)
Nirmatrelvir combined with ritonavir is indicated for the treatment of mild-to-moderate COVID-19. The study did not demonstrate a significant difference in the time to relief of COVID-19 signs and symptoms between the treatment and placebo groups.
Of the 1,296 participants randomized, 1,288 received at least one dose of nirmatrelvirâritonavir (654 participants) or placebo (634 participants) and had a follow-up visit post-baseline. The median time to alleviate all specified COVID-19 signs and symptoms was 12 days in the nirmatrelvirâritonavir group and 13 days in the placebo group (P=0.60). Hospitalization or death occurred in 0.8% of the nirmatrelvirâritonavir group compared to 1.6% in the placebo group. Adverse events were reported in 25.8% of the nirmatrelvirâritonavir group and 24.1% of the placebo group, with taste disturbances (5.8%) and diarrhea (2.1%) being the most common in the treatment group.
âAmong the patients who underwent randomization, COVIDâ19ârelated hospitalization or death from any cause occurred in 5 participants in the nirmatrelvirâritonavir group and 10 in the placebo group,â according to investigators. âIn the subgroup of high-risk participants, the numbers with this outcome were 3 and 7, respectively.â1
Main Takeaways
- Study found a minimal difference in the time to alleviate all specified COVID-19 signs and symptoms between the treatment group (nirmatrelvirâritonavir) and the placebo group.
- Despite the primary endpoint of symptom alleviation time not showing a significant difference, the study observed a low percentage of hospitalizations or deaths in the nirmatrelvirâritonavir group (0.8%) compared to the placebo group (1.6%).
- The adverse events reported were similar between the nirmatrelvirâritonavir and the placebo group, with taste disturbances and diarrhea being the most common in the treatment group.
In this phase 2â3 trial, adults with confirmed COVID-19 and symptom onset within the last 5 days were randomized to receive nirmatrelvirâritonavir or a placebo every 12 hours for 5 days. Eligibility included the fully vaccinated individuals with at least one risk factor for severe COVID-19 and unvaccinated individuals or those not vaccinated within the past year, irrespective of risk factors. The primary outcome was the time to sustain the alleviation of all targeted signs and symptoms of COVID-19.
âThe results with respect to the numbers of Covid-19ârelated hospitalizations and deaths from any cause in this trial, although not significant, are consistent with and supported by recent real-world data,â according to investigators. â5 real-world cohort studies have investigated nirmatrelvirâritonavir in SARS-CoV-2âpositive nonhospitalized patients during the period of omicron-variant dominance.â1
Limitations include a descriptive analysis for the key secondary outcome due to the primary efficacy endpoint not being met and potential bias in blinding due to the distinct taste of nirmatrelvirâritonavir. The trial’s initiation during the delta variant’s predominance. However, this is mitigated by subsequent studies affirming nirmatrelvirâritonavir’s efficacy across different SARS-CoV-2 strains.
According to a previous report from Contagion, a Veterans Affairs study finds some reduction in post-COVID thromboembolic events with early use of nirmatrelvir-ritonavir but no protection against 30 other conditions.
âUse of the antiviral combination nirmatrelvir-ritonavir (Paxlovid) for early symptoms of COVID-19 offered limited protection against the development of Long COVID, in a VA study finding some reduced risk for thromboembolic events but not for 30 other potential post-COVID conditions.â2
Given the challenges such as waning vaccine immunity and emerging variants, the diverse international participant pool and the continued relevance of findings underscore the need for effective treatments for high-risk populations in the ongoing management of COVID-19.
References
- Hammond J, Fountaine R, Yunis C, et. al. Nirmatrelvir for Vaccinated or Unvaccinated Adult Outpatients with Covid-19. Published April 3, 2024. Accessed April 9, 2024. The New England Journal of Medicine. Doi: 10.1056/NEJMoa2309003
- Bender K. Paxlovid Provides Limited Protection Against Long COVID. Contagion. Published October 31, 2023. Accessed April 9, 2024. https://www.contagionlive.com/view/paxlovid-provides-limited-protection-against-long-covid