Oral Nirmatrelvir-Ritonavir as Postexposure Prophylaxis for Covid-19.
Jennifer Hammond, Carla Yunis, Robert J Fountaine, Gerald Luscan, Aimee M Burr, Wuyan Zhang, Wayne Wisemandle, Holly Soares, Mary Lynn Baniecki, Victoria M Hendrick, Veselin Kalfov, Rienk Pypstra, James M Rusnak
Author Information
Jennifer Hammond: From Global Product Development, Pfizer, Collegeville, PA (J.H.); Global Product Development, Pfizer, Lake Mary (C.Y.), and Global Product Development, Pfizer, Tampa (J.M.R.) - both in Florida; Global Product Development, Pfizer, Groton, CT (R.J.F., H.S.); Global Product Development, Pfizer International Organization, Paris (G.L.); Pfizer, Chicago (A.M.B.); Global Product Development, Pfizer, Lake Forest, IL (W.Z., W.W.); Early Clinical Development, Pfizer, Cambridge, MA (M.L.B.); Medical and Safety, Pfizer Research and Development UK, Sandwich, United Kingdom (V.M.H.); Specialized Hospital for Active Treatment of Pneumo-Phthisiatric Diseases, Haskovo, Bulgaria (V.K.); and Global Product Development, Pfizer, New York (R.P.).
Carla Yunis: From Global Product Development, Pfizer, Collegeville, PA (J.H.); Global Product Development, Pfizer, Lake Mary (C.Y.), and Global Product Development, Pfizer, Tampa (J.M.R.) - both in Florida; Global Product Development, Pfizer, Groton, CT (R.J.F., H.S.); Global Product Development, Pfizer International Organization, Paris (G.L.); Pfizer, Chicago (A.M.B.); Global Product Development, Pfizer, Lake Forest, IL (W.Z., W.W.); Early Clinical Development, Pfizer, Cambridge, MA (M.L.B.); Medical and Safety, Pfizer Research and Development UK, Sandwich, United Kingdom (V.M.H.); Specialized Hospital for Active Treatment of Pneumo-Phthisiatric Diseases, Haskovo, Bulgaria (V.K.); and Global Product Development, Pfizer, New York (R.P.).
Robert J Fountaine: From Global Product Development, Pfizer, Collegeville, PA (J.H.); Global Product Development, Pfizer, Lake Mary (C.Y.), and Global Product Development, Pfizer, Tampa (J.M.R.) - both in Florida; Global Product Development, Pfizer, Groton, CT (R.J.F., H.S.); Global Product Development, Pfizer International Organization, Paris (G.L.); Pfizer, Chicago (A.M.B.); Global Product Development, Pfizer, Lake Forest, IL (W.Z., W.W.); Early Clinical Development, Pfizer, Cambridge, MA (M.L.B.); Medical and Safety, Pfizer Research and Development UK, Sandwich, United Kingdom (V.M.H.); Specialized Hospital for Active Treatment of Pneumo-Phthisiatric Diseases, Haskovo, Bulgaria (V.K.); and Global Product Development, Pfizer, New York (R.P.).
Gerald Luscan: From Global Product Development, Pfizer, Collegeville, PA (J.H.); Global Product Development, Pfizer, Lake Mary (C.Y.), and Global Product Development, Pfizer, Tampa (J.M.R.) - both in Florida; Global Product Development, Pfizer, Groton, CT (R.J.F., H.S.); Global Product Development, Pfizer International Organization, Paris (G.L.); Pfizer, Chicago (A.M.B.); Global Product Development, Pfizer, Lake Forest, IL (W.Z., W.W.); Early Clinical Development, Pfizer, Cambridge, MA (M.L.B.); Medical and Safety, Pfizer Research and Development UK, Sandwich, United Kingdom (V.M.H.); Specialized Hospital for Active Treatment of Pneumo-Phthisiatric Diseases, Haskovo, Bulgaria (V.K.); and Global Product Development, Pfizer, New York (R.P.).
Aimee M Burr: From Global Product Development, Pfizer, Collegeville, PA (J.H.); Global Product Development, Pfizer, Lake Mary (C.Y.), and Global Product Development, Pfizer, Tampa (J.M.R.) - both in Florida; Global Product Development, Pfizer, Groton, CT (R.J.F., H.S.); Global Product Development, Pfizer International Organization, Paris (G.L.); Pfizer, Chicago (A.M.B.); Global Product Development, Pfizer, Lake Forest, IL (W.Z., W.W.); Early Clinical Development, Pfizer, Cambridge, MA (M.L.B.); Medical and Safety, Pfizer Research and Development UK, Sandwich, United Kingdom (V.M.H.); Specialized Hospital for Active Treatment of Pneumo-Phthisiatric Diseases, Haskovo, Bulgaria (V.K.); and Global Product Development, Pfizer, New York (R.P.).
Wuyan Zhang: From Global Product Development, Pfizer, Collegeville, PA (J.H.); Global Product Development, Pfizer, Lake Mary (C.Y.), and Global Product Development, Pfizer, Tampa (J.M.R.) - both in Florida; Global Product Development, Pfizer, Groton, CT (R.J.F., H.S.); Global Product Development, Pfizer International Organization, Paris (G.L.); Pfizer, Chicago (A.M.B.); Global Product Development, Pfizer, Lake Forest, IL (W.Z., W.W.); Early Clinical Development, Pfizer, Cambridge, MA (M.L.B.); Medical and Safety, Pfizer Research and Development UK, Sandwich, United Kingdom (V.M.H.); Specialized Hospital for Active Treatment of Pneumo-Phthisiatric Diseases, Haskovo, Bulgaria (V.K.); and Global Product Development, Pfizer, New York (R.P.).
Wayne Wisemandle: From Global Product Development, Pfizer, Collegeville, PA (J.H.); Global Product Development, Pfizer, Lake Mary (C.Y.), and Global Product Development, Pfizer, Tampa (J.M.R.) - both in Florida; Global Product Development, Pfizer, Groton, CT (R.J.F., H.S.); Global Product Development, Pfizer International Organization, Paris (G.L.); Pfizer, Chicago (A.M.B.); Global Product Development, Pfizer, Lake Forest, IL (W.Z., W.W.); Early Clinical Development, Pfizer, Cambridge, MA (M.L.B.); Medical and Safety, Pfizer Research and Development UK, Sandwich, United Kingdom (V.M.H.); Specialized Hospital for Active Treatment of Pneumo-Phthisiatric Diseases, Haskovo, Bulgaria (V.K.); and Global Product Development, Pfizer, New York (R.P.).
Holly Soares: From Global Product Development, Pfizer, Collegeville, PA (J.H.); Global Product Development, Pfizer, Lake Mary (C.Y.), and Global Product Development, Pfizer, Tampa (J.M.R.) - both in Florida; Global Product Development, Pfizer, Groton, CT (R.J.F., H.S.); Global Product Development, Pfizer International Organization, Paris (G.L.); Pfizer, Chicago (A.M.B.); Global Product Development, Pfizer, Lake Forest, IL (W.Z., W.W.); Early Clinical Development, Pfizer, Cambridge, MA (M.L.B.); Medical and Safety, Pfizer Research and Development UK, Sandwich, United Kingdom (V.M.H.); Specialized Hospital for Active Treatment of Pneumo-Phthisiatric Diseases, Haskovo, Bulgaria (V.K.); and Global Product Development, Pfizer, New York (R.P.). ORCID
Mary Lynn Baniecki: From Global Product Development, Pfizer, Collegeville, PA (J.H.); Global Product Development, Pfizer, Lake Mary (C.Y.), and Global Product Development, Pfizer, Tampa (J.M.R.) - both in Florida; Global Product Development, Pfizer, Groton, CT (R.J.F., H.S.); Global Product Development, Pfizer International Organization, Paris (G.L.); Pfizer, Chicago (A.M.B.); Global Product Development, Pfizer, Lake Forest, IL (W.Z., W.W.); Early Clinical Development, Pfizer, Cambridge, MA (M.L.B.); Medical and Safety, Pfizer Research and Development UK, Sandwich, United Kingdom (V.M.H.); Specialized Hospital for Active Treatment of Pneumo-Phthisiatric Diseases, Haskovo, Bulgaria (V.K.); and Global Product Development, Pfizer, New York (R.P.).
Victoria M Hendrick: From Global Product Development, Pfizer, Collegeville, PA (J.H.); Global Product Development, Pfizer, Lake Mary (C.Y.), and Global Product Development, Pfizer, Tampa (J.M.R.) - both in Florida; Global Product Development, Pfizer, Groton, CT (R.J.F., H.S.); Global Product Development, Pfizer International Organization, Paris (G.L.); Pfizer, Chicago (A.M.B.); Global Product Development, Pfizer, Lake Forest, IL (W.Z., W.W.); Early Clinical Development, Pfizer, Cambridge, MA (M.L.B.); Medical and Safety, Pfizer Research and Development UK, Sandwich, United Kingdom (V.M.H.); Specialized Hospital for Active Treatment of Pneumo-Phthisiatric Diseases, Haskovo, Bulgaria (V.K.); and Global Product Development, Pfizer, New York (R.P.).
Veselin Kalfov: From Global Product Development, Pfizer, Collegeville, PA (J.H.); Global Product Development, Pfizer, Lake Mary (C.Y.), and Global Product Development, Pfizer, Tampa (J.M.R.) - both in Florida; Global Product Development, Pfizer, Groton, CT (R.J.F., H.S.); Global Product Development, Pfizer International Organization, Paris (G.L.); Pfizer, Chicago (A.M.B.); Global Product Development, Pfizer, Lake Forest, IL (W.Z., W.W.); Early Clinical Development, Pfizer, Cambridge, MA (M.L.B.); Medical and Safety, Pfizer Research and Development UK, Sandwich, United Kingdom (V.M.H.); Specialized Hospital for Active Treatment of Pneumo-Phthisiatric Diseases, Haskovo, Bulgaria (V.K.); and Global Product Development, Pfizer, New York (R.P.).
Rienk Pypstra: From Global Product Development, Pfizer, Collegeville, PA (J.H.); Global Product Development, Pfizer, Lake Mary (C.Y.), and Global Product Development, Pfizer, Tampa (J.M.R.) - both in Florida; Global Product Development, Pfizer, Groton, CT (R.J.F., H.S.); Global Product Development, Pfizer International Organization, Paris (G.L.); Pfizer, Chicago (A.M.B.); Global Product Development, Pfizer, Lake Forest, IL (W.Z., W.W.); Early Clinical Development, Pfizer, Cambridge, MA (M.L.B.); Medical and Safety, Pfizer Research and Development UK, Sandwich, United Kingdom (V.M.H.); Specialized Hospital for Active Treatment of Pneumo-Phthisiatric Diseases, Haskovo, Bulgaria (V.K.); and Global Product Development, Pfizer, New York (R.P.).
James M Rusnak: From Global Product Development, Pfizer, Collegeville, PA (J.H.); Global Product Development, Pfizer, Lake Mary (C.Y.), and Global Product Development, Pfizer, Tampa (J.M.R.) - both in Florida; Global Product Development, Pfizer, Groton, CT (R.J.F., H.S.); Global Product Development, Pfizer International Organization, Paris (G.L.); Pfizer, Chicago (A.M.B.); Global Product Development, Pfizer, Lake Forest, IL (W.Z., W.W.); Early Clinical Development, Pfizer, Cambridge, MA (M.L.B.); Medical and Safety, Pfizer Research and Development UK, Sandwich, United Kingdom (V.M.H.); Specialized Hospital for Active Treatment of Pneumo-Phthisiatric Diseases, Haskovo, Bulgaria (V.K.); and Global Product Development, Pfizer, New York (R.P.).
BACKGROUND: Clinical trials of treatments for coronavirus disease 2019 (Covid-19) have not shown a significant benefit of postexposure prophylaxis. METHODS: We conducted a phase 2-3 double-blind trial to assess the efficacy and safety of nirmatrelvir-ritonavir in asymptomatic, rapid antigen test-negative adults who had been exposed to a household contact with Covid-19 within 96 hours before randomization. The participants were randomly assigned in a 1:1:1 ratio to receive nirmatrelvir-ritonavir (300 mg of nirmatrelvir and 100 mg of ritonavir) every 12 hours for 5 days or for 10 days or matching placebo for 5 or 10 days. The primary end point was the development of symptomatic SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection, confirmed on reverse-transcriptase-polymerase-chain-reaction (RT-PCR) or rapid antigen testing, through 14 days in participants who had a negative RT-PCR test at baseline. RESULTS: A total of 2736 participants were randomly assigned to a trial group - 921 to the 5-day nirmatrelvir-ritonavir group, 917 to the 10-day nirmatrelvir-ritonavir group, and 898 to the placebo group. Symptomatic, confirmed SARS-CoV-2 infection developed by day 14 in 2.6% of the participants in the 5-day nirmatrelvir-ritonavir group, 2.4% of those in the 10-day nirmatrelvir-ritonavir group, and 3.9% of those in the placebo group. In each nirmatrelvir-ritonavir group, the percentage of participants in whom symptomatic, confirmed SARS-CoV-2 infection developed did not differ significantly from that in the placebo group, with risk reductions relative to placebo of 29.8% (95% confidence interval [CI], -16.7 to 57.8; P���=���0.17) in the 5-day nirmatrelvir-ritonavir group and 35.5% (95% CI, -11.5 to 62.7; P���=���0.12) in the 10-day nirmatrelvir-ritonavir group. The incidence of adverse events was similar across the trial groups, with dysgeusia being the most frequently reported adverse event (in 5.9% and 6.8% of the participants in the 5-day and 10-day nirmatrelvir-ritonavir groups, respectively, and in 0.7% of those in the placebo group). CONCLUSIONS: In this placebo-controlled trial, postexposure prophylaxis with nirmatrelvir-ritonavir for 5 or 10 days did not significantly reduce the risk of symptomatic SARS-CoV-2 infection. (Funded by Pfizer; ClinicalTrials.gov number, NCT05047601.).
