Oral Nirmatrelvir–Ritonavir for Covid-19 in Higher-Risk Outpatients

Butler et al., New England Journal of Medicine, doi:10.1056/NEJMoa2502457 (results released 9/10/2025), CanTreatCOVID, NCT05614349, Sep 2025
Early treatmentRCT · 667 patients · UK · Dec 2021 – Sep 2024
Paxlovid for COVID-19
Outcome
Improvement
Relative Risk · 95% CI
Improved recovery with paxlovid
p = 0.000018
Results for the CanTreatCOVID trial. See Butler et al. for details.
Standard of Care (SOC) for COVID-19 in the study country, the United Kingdom, is very poor with very low average efficacy for approved treatments2. The United Kingdom focused on expensive high-profit treatments, approving only one low-cost early treatment, which required a prescription and had limited adoption. The high-cost prescription treatment strategy reduces the probability of early treatment due to access and cost barriers, and eliminates complementary and synergistic benefits seen with many low-cost treatments.
OutcomeImprovementEffect · pTreatmentControl
risk of death/hospitalization 51.7% lower · RR 0.48 · p = 0.39 51.7% lowerRR 0.48p = 0.39 2 of 343 (0.6%) 4 of 324 (1.2%) treatment 2 of 343 (0.6%), control 4 of 324 (1.2%)NNT 153odds ratio converted to relative riskday 28
risk of no recovery 42.2% lower · RR 0.58 · p < 0.001*** 42.2% lowerRR 0.58p < 0.001*** 73 of 345 (21.2%) 112 of 306 (36.6%) treatment 73 of 345 (21.2%), control 112 of 306 (36.6%)NNT 6.5day 14
risk of no recovery 34.4% lower · RR 0.66 · p < 0.001*** 34.4% lowerRR 0.66p < 0.001*** 86 of 277 (31.0%) 115 of 245 (46.9%) treatment 86 of 277 (31.0%), control 115 of 245 (46.9%)no early sustained recoveryNNT 6.3inverted to make RR<1 favor treatmentodds ratio converted to relative risk
recovery time 33.3% lower · relative time 0.67 · 33.3% lowerrelative time 0.67 343 324 treatment 343, control 324

Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates. *** p < 0.001

Butler et al., 10 Sep 2025, Randomized Controlled Trial, United Kingdom, peer-reviewed, 42 authors, study period 8 December, 2021 - 30 September, 2024, trial NCT05614349 (history) (CanTreatCOVID).
$0 $500 $1,000+ Efficacy vs. cost for COVID-19 treatment protocols c19early.org November 2026 United Kingdom Angola Colombia Kenya Mozambique Myanmar South Africa Peru Philippines USA Brazil France Italy Canada Pakistan Spain Vietnam Japan Nepal Iran Bangladesh Ethiopia Ghana Mexico South Korea Saudi Arabia Algeria Morocco Yemen Poland Uzbekistan India China Venezuela DR Congo Madagascar Thailand Uganda Egypt Nigeria Taiwan Fiji Zambia Bosnia-Herzegovina Dominican Republic Bolivia Côte d'Ivoire Eritrea Togo Iceland New Zealand Mongolia Czechia Belarus Israel Haiti North Macedonia Hong Kong Qatar Panama Serbia The United Kingdom favored high-profit treatments.The average efficacy of treatments was moderate.High-cost protocols reduce early treatment, andforgo complementary/synergistic benefits. More effective More expensive 75% 50% 25% ≤0%
$0 $500 $1,000+ Efficacy vs. cost for COVID-19treatment protocols worldwide c19early.org November 2026 United Kingdom Angola Colombia Kenya Mozambique Myanmar South Africa Peru Philippines USA Brazil France Italy Canada Pakistan Spain Vietnam Japan Iran Bangladesh Ethiopia Ghana Mexico South Korea Saudi Arabia Algeria Morocco Yemen Poland Uzbekistan India China Venezuela DR Congo Madagascar Thailand Uganda Egypt Taiwan Fiji Zambia Dominican Rep. Bolivia Côte d'Ivoire Eritrea Mongolia Czechia Belarus Israel North Macedonia Hong Kong Qatar Panama Serbia The UK favored high-profit treatments.The average efficacy was moderate.High-cost protocols reduce early treatment,and forgo complementary/synergistic benefits. More effective More expensive 75% 50% 25% ≤0%
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