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All Studies   All Outcomes    Recent:   

Oral Nirmatrelvir for High-Risk, Nonhospitalized Adults with Covid-19

Hammond et al., New England Journal of Medicine, doi:10.1056/NEJMoa2118542, EPIC-HR, NCT04960202
Feb 2022  
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0 0.5 1 1.5 2+ Mortality 96% Improvement Relative Risk Mortality (b) 95% Hospitalization 88% Hospitalization (b) 89% Progression -11% Recovery time 21% Viral load, day 10 12% Viral load, day 14 5% Paxlovid  EPIC-HR  EARLY TREATMENT  DB RCT Is early treatment with paxlovid beneficial for COVID-19? Double-blind RCT 2,085 patients in multiple countries (Jul - Dec 2021) Lower mortality (p=0.00047) and hospitalization (p<0.0001) c19early.org Hammond et al., New England J. Medicine, Feb 2022 Favors paxlovid Favors control
EPIC-HR RCT, 1,039 higher risk patients treated with paxlovid (PF-07321332 + ritonavir) and 1,046 control patients, showing significantly lower mortality and hospitalization with treatment.
risk of death, 96.0% lower, RR 0.04, p < 0.001, treatment 0 of 1,039 (0.0%), control 12 of 1,046 (1.1%), NNT 87, relative risk is not 0 because of continuity correction due to zero events (with reciprocal of the contrasting arm), within 5 days.
risk of death, 94.8% lower, RR 0.05, p = 0.002, treatment 0 of 697 (0.0%), control 9 of 682 (1.3%), NNT 76, relative risk is not 0 because of continuity correction due to zero events (with reciprocal of the contrasting arm), within 3 days.
risk of hospitalization, 87.6% lower, RR 0.12, p < 0.001, treatment 8 of 1,039 (0.8%), control 65 of 1,046 (6.2%), NNT 18, within 5 days.
risk of hospitalization, 88.9% lower, RR 0.11, p < 0.001, treatment 5 of 697 (0.7%), control 44 of 682 (6.5%), NNT 17, within 3 days.
risk of progression, 10.8% higher, OR 1.11, p = 0.45, treatment 686, control 674, from registry results, day 28, RR approximated with OR.
recovery time, 21.1% lower, relative time 0.79, p < 0.001, treatment 686, control 674, inverted to make RR<1 favor treatment, from registry results.
viral load, 12.1% lower, relative load 0.88, p < 0.001, treatment mean 4.532 (±2.101) n=529, control mean 3.984 (±2.109) n=526, from registry results, day 10.
viral load, 5.1% lower, relative load 0.95, p = 0.048, treatment mean 5.098 (±2.129) n=529, control mean 4.84 (±2.111) n=526, from registry results, day 14.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Hammond et al., 16 Feb 2022, Double Blind Randomized Controlled Trial, placebo-controlled, multiple countries, peer-reviewed, 12 authors, study period 16 July, 2021 - 9 December, 2021, average treatment delay 2.93 days, trial NCT04960202 (history) (EPIC-HR).
This PaperPaxlovidAll
Oral Nirmatrelvir for High-Risk, Nonhospitalized Adults with Covid-19
Ph.D Jennifer Hammond, Heidi Leister-Tebbe, M.P.H Annie Gardner, M.S.P.T Paula Abreu, Ph.D Weihang Bao, Ph.D Wayne Wisemandle, Ph.D Marylynn Baniecki, B.Sc Victoria M Hendrick, Ph.D Bharat Damle, M.D Abraham Simón-Campos, M.D Rienk Pypstra, M.D James M Rusnak
New England Journal of Medicine, doi:10.1056/nejmoa2118542
BACKGROUND Nirmatrelvir is an orally administered severe acute respiratory syndrome coronavirus 2 main protease (M pro ) inhibitor with potent pan-human-coronavirus activity in vitro. METHODS We conducted a phase 2-3 double-blind, randomized, controlled trial in which symptomatic, unvaccinated, nonhospitalized adults at high risk for progression to severe coronavirus disease 2019 (Covid-19) were assigned in a 1:1 ratio to receive either 300 mg of nirmatrelvir plus 100 mg of ritonavir (a pharmacokinetic enhancer) or placebo every 12 hours for 5 days. Covid-19-related hospitalization or death from any cause through day 28, viral load, and safety were evaluated. RESULTS A total of 2246 patients underwent randomization; 1120 patients received nirmatrelvir plus ritonavir (nirmatrelvir group) and 1126 received placebo (placebo group). In the planned interim analysis of patients treated within 3 days after symptom onset (modified intention-to treat population, comprising 774 of the 1361 patients in the full analysis population), the incidence of Covid-19-related hospitalization or death by day 28 was lower in the nirmatrelvir group than in the placebo group by 6.32 percentage points (95% confidence interval [CI], −9.04 to −3.59; P<0.001; relative risk reduction, 89.1%); the incidence was 0.77% (3 of 389 patients) in the nirmatrelvir group, with 0 deaths, as compared with 7.01% (27 of 385 patients) in the placebo group, with 7 deaths. Efficacy was maintained in the final analysis involving the 1379 patients in the modified intention-to-treat population, with a difference of −5.81 percentage points (95% CI, −7.78 to −3.84; P<0.001; relative risk reduction, 88.9%). All 13 deaths occurred in the placebo group. The viral load was lower with nirmaltrelvir plus ritonavir than with placebo at day 5 of treatment, with an adjusted mean difference of −0.868 log 10 copies per milliliter when treatment was initiated within 3 days after the onset of symptoms. The incidence of adverse events that emerged during the treatment period was similar in the two groups (any adverse event, 22.6% with nirmatrelvir plus ritonavir vs. 23.9% with placebo; serious adverse events, 1.6% vs. 6.6%; and adverse events leading to discontinuation of the drugs or placebo, 2.1% vs. 4.2%). Dysgeusia (5.6% vs. 0.3%) and diarrhea (3.1% vs. 1.6%) occurred more frequently with nirmatrelvir plus ritonavir than with placebo. CONCLUSIONS Treatment of symptomatic Covid-19 with nirmatrelvir plus ritonavir resulted in a risk of progression to severe Covid-19 that was 89% lower than the risk with placebo, without evident safety concerns. (Supported by Pfizer; ClinicalTrials.gov number, NCT04960202.
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