Nirmatrelvir for Vaccinated or Unvaccinated Adult Outpatients with Covid-19
et al., New England Journal of Medicine, doi:10.1056/NEJMoa2309003 (results released 6/14/2022), EPIC-SR, NCT05011513, Jun 2022
Delayed publication for EPIC-SR showing no significant difference in time to sustained alleviation. Selected results were made available in December 2021 and June 2022. Some results are only available in the registry and are missing in the paper.
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risk of death, 67.0% lower, RR 0.33, p = 0.49, treatment 0 of 654 (0.0%), control 1 of 634 (0.2%), NNT 634, relative risk is not 0 because of continuity correction due to zero events (with reciprocal of the contrasting arm), day 28.
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risk of hospitalization, 51.5% lower, RR 0.48, p = 0.20, treatment 5 of 654 (0.8%), control 10 of 634 (1.6%), NNT 123, day 28.
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risk of severe case, 11.5% lower, RR 0.88, p = 0.27, treatment 125 of 654 (19.1%), control 137 of 634 (21.6%), NNT 40, severe signs or symptoms, day 28.
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risk of progression, 3.8% lower, RR 0.96, p = 0.21, treatment 494 of 654 (75.5%), control 498 of 634 (78.5%), NNT 33, progression to worsening status, day 28.
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risk of progression, 41.8% lower, RR 0.58, p = 0.11, treatment 15 of 654 (2.3%), control 25 of 634 (3.9%), NNT 61, medical visits, day 28.
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relative time to sustained alleviation, 2.1% lower, relative time 0.98, p = 0.60, treatment 654, control 634.
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relative change in viral load, 3.9% better, RR 0.96, p = 0.04, treatment mean 5.46 (±1.84) n=654, control mean 5.25 (±1.89) n=634, day 14.
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| Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates |
Hammond et al., 14 Jun 2022, Double Blind Randomized Controlled Trial, multiple countries, peer-reviewed, 13 authors, study period 25 August, 2021 - 25 July, 2022, trial NCT05011513 (history) (EPIC-SR).
Abstract: From Global Product Development, Pfizer, Collegeville, PA (J.H.); Global Product Development, Pfizer, Groton, CT (R.J.F.); Global Product Development, Pfizer, Lake Mary (C.Y.), and Global Product Development, Pfizer, Tampa (J.M.R.) - both in Florida; Global Product Development, Pfizer, Lexington, KY (D.F.); Global Product Development, Pfizer, New York (M.A., W.B., R.P.); Global Product Development, Pfizer, Lake Forest, IL (W.W.); Early Clinical Development, Pfizer, Cambridge, MA (M.L.B.); Pfizer, Sandwich, United Kingdom (V.M.H.); the Specialized Hospital for Active Treatment of Pneumo-Phthisiatric Diseases, Haskovo, Bulgaria (V.K.); and Méchnikov Project, Köhler and Milstein Research, Anahuac-Mayab University, Mérida, Mexico (J.A.S.-C.). Dr. Hammond can be contacted at jennifer . hammond@ pfizer . com or at Global Product Development, Pfizer, 500 Arcola Rd., Collegeville, PA 19426.
*A list of the investigators in the EPIC-SR trial is provided in the Supplementary Appendix, available at NEJM.org.
N Engl J Med 2024;390:1186-95. DOI: 10.1056/NEJMoa2309003 Copyright © 2024 Massachusetts Medical Society.
BACKGROUND
Nirmatrelvir in combination with ritonavir is an antiviral treatment for mild-tomoderate coronavirus disease 2019 (Covid-19). The efficacy of this treatment in patients who are at standard risk for severe Covid-19 or who are fully vaccinated and have at least one risk factor for severe Covid-19 has not been established.
METHODS
In this phase 2-3 trial, we randomly assigned adults who had confirmed Covid-19 with symptom onset within the past 5 days in a 1:1 ratio to receive nirmatrelvirritonavir or placebo every 12 hours for 5 days. Patients who were fully vaccinated against Covid-19 and who had at least one risk factor for severe disease, as well as patients without such risk factors who had never been vaccinated against Covid-19 or had not been vaccinated within the previous year, were eligible for participation. Participants logged the presence and severity of prespecified Covid-19 signs and symptoms daily from day 1 through day 28. The primary end point was the time to sustained alleviation of all targeted Covid-19 signs and symptoms. Covid-19-related hospitalization and death from any cause were also assessed through day 28.
RESULTS
Among the 1296 participants who underwent randomization and were included in the full analysis population, 1288 received at least one dose of nirmatrelvir-ritonavir (654 participants) or placebo (634 participants) and had at least one postbaseline visit. The median time to sustained alleviation of all targeted signs and symptoms of Covid-19 was 12 days in the nirmatrelvir-ritonavir group and 13 days in the placebo group (P = 0.60). Five participants (0.8%) in the nirmatrelvir-ritonavir group and 10 (1.6%) in the placebo group were hospitalized for Covid-19 or died from any cause (difference, -0.8 percentage points; 95% confidence interval, -2.0 to 0.4). The percentages of participants with adverse events were similar in the two groups (25.8% with nirmatrelvir-ritonavir and 24.1% with placebo). In the nirmatrelvir-ritonavir group, the most commonly reported treatment-related adverse events were dysgeusia (in 5.8% of the participants) and diarrhea (in 2.1%).
CONCLUSIONS
The time to sustained alleviation of all signs and symptoms of Covid-19 did not differ significantly between participants who received nirmatrelvir-ritonavir and those who received..
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