tetano
Editor, Senior Moderator
Trials
. 2025 Nov 6;26(1):477.
doi: 10.1186/s13063-025-09226-6. Randomized trial of nirmatrelvir/ritonavir versus placebo for adults with acute COVID-19 to prevent long COVID: PanoramicNOR Trial
Bjørn Blomberg[SUP] 1 2 [/SUP], Nikolai Norevik Myklebust[SUP] 3 4 [/SUP], Oddvar Oppegaard[SUP] 3 4 [/SUP], Camilla Tøndel[SUP] 3 5 [/SUP], Rebecca Jane Cox[SUP] 3 6 [/SUP], Arild Iversen[SUP] 3 7 [/SUP], Marianne Emblem Lehmann[SUP] 3 [/SUP], Axel Sandvig[SUP] 8 9 [/SUP], Tuva Børresdatter Dahl[SUP] 10 [/SUP], Vibeke Devold Valderhaug[SUP] 11 12 [/SUP], Peter Szodoray[SUP] 13 [/SUP], Maja Wilhelmsen[SUP] 14 15 [/SUP], Bjørn Eivind Kirsebom[SUP] 16 17 [/SUP], Marte Glambek[SUP] 3 4 [/SUP], Oddvar Kaarbøe[SUP] 18 [/SUP], Pål Aukrust[SUP] 10 19 [/SUP], Rolv Terje Lie[SUP] 18 [/SUP], Nina Langeland[SUP] 3 20 [/SUP]
Affiliations
Background: The high prevalence of long-term persisting symptoms after COVID-19 (coronavirus disease 2019), termed long COVID or post-COVID-19 condition, even among those with mild initial disease, may have a large public health impact. Apart from avoiding infection, there is no proven prevention or treatment for long COVID. We will perform a randomized placebo-controlled clinical trial to assess whether treatment with the novel antiviral, nirmatrelvir and ritonavir (Paxlovid®) for acute COVID-19 can prevent the development of long COVID.
Methods: This is a randomized double-blinded placebo-controlled trial that aims to recruit 2000 nonpregnant persons aged 18 to 64 years with acute COVID-19 with positive PCR and/or antigen test and symptom duration of not more than 5 days. Participants will be randomized 1:1 to a 5-day course of Paxlovid (two tablets 150-mg nirmatrelvir and one tablet 100-mg ritonavir twice daily) or a 5-day course of placebo (similar number of tablets of equal appearance). The primary endpoint will be persistent symptoms compatible with long COVID, assessed as the prevalence of a dichotomous variable corresponding to the presence (1) or absence (0) of one or more of the following symptoms: (i) fatigue, (ii) dyspnea, and (iii) cognitive symptoms (memory and/or concentration problems). The primary outcome will be evaluated at 3-month follow-up and then re-evaluated at 6, 12, and 24 months.
Discussion: As more than 750 million people with confirmed COVID-19 have survived globally, the potential burden of long COVID on societies is formidable. If a simple 5-day oral treatment course with nirmatrelvir/ritonavir is shown to prevent long COVID, it would be a highly attractive intervention at an individual level and a mitigation of its public health consequences.
Trial registration: ClinicalTrials.gov NCT05852873. Registered on May 2023.
Keywords: COVID-19; Long COVID; Nirmatrelvir/ritonavir; Paxlovid; Post-COVID-19 condition; Prevention; Randomized controlled trial; SARS-CoV-2.
. 2025 Nov 6;26(1):477.
doi: 10.1186/s13063-025-09226-6. Randomized trial of nirmatrelvir/ritonavir versus placebo for adults with acute COVID-19 to prevent long COVID: PanoramicNOR Trial
Bjørn Blomberg[SUP] 1 2 [/SUP], Nikolai Norevik Myklebust[SUP] 3 4 [/SUP], Oddvar Oppegaard[SUP] 3 4 [/SUP], Camilla Tøndel[SUP] 3 5 [/SUP], Rebecca Jane Cox[SUP] 3 6 [/SUP], Arild Iversen[SUP] 3 7 [/SUP], Marianne Emblem Lehmann[SUP] 3 [/SUP], Axel Sandvig[SUP] 8 9 [/SUP], Tuva Børresdatter Dahl[SUP] 10 [/SUP], Vibeke Devold Valderhaug[SUP] 11 12 [/SUP], Peter Szodoray[SUP] 13 [/SUP], Maja Wilhelmsen[SUP] 14 15 [/SUP], Bjørn Eivind Kirsebom[SUP] 16 17 [/SUP], Marte Glambek[SUP] 3 4 [/SUP], Oddvar Kaarbøe[SUP] 18 [/SUP], Pål Aukrust[SUP] 10 19 [/SUP], Rolv Terje Lie[SUP] 18 [/SUP], Nina Langeland[SUP] 3 20 [/SUP]
Affiliations
- PMID: 41199272
- DOI: 10.1186/s13063-025-09226-6
Background: The high prevalence of long-term persisting symptoms after COVID-19 (coronavirus disease 2019), termed long COVID or post-COVID-19 condition, even among those with mild initial disease, may have a large public health impact. Apart from avoiding infection, there is no proven prevention or treatment for long COVID. We will perform a randomized placebo-controlled clinical trial to assess whether treatment with the novel antiviral, nirmatrelvir and ritonavir (Paxlovid®) for acute COVID-19 can prevent the development of long COVID.
Methods: This is a randomized double-blinded placebo-controlled trial that aims to recruit 2000 nonpregnant persons aged 18 to 64 years with acute COVID-19 with positive PCR and/or antigen test and symptom duration of not more than 5 days. Participants will be randomized 1:1 to a 5-day course of Paxlovid (two tablets 150-mg nirmatrelvir and one tablet 100-mg ritonavir twice daily) or a 5-day course of placebo (similar number of tablets of equal appearance). The primary endpoint will be persistent symptoms compatible with long COVID, assessed as the prevalence of a dichotomous variable corresponding to the presence (1) or absence (0) of one or more of the following symptoms: (i) fatigue, (ii) dyspnea, and (iii) cognitive symptoms (memory and/or concentration problems). The primary outcome will be evaluated at 3-month follow-up and then re-evaluated at 6, 12, and 24 months.
Discussion: As more than 750 million people with confirmed COVID-19 have survived globally, the potential burden of long COVID on societies is formidable. If a simple 5-day oral treatment course with nirmatrelvir/ritonavir is shown to prevent long COVID, it would be a highly attractive intervention at an individual level and a mitigation of its public health consequences.
Trial registration: ClinicalTrials.gov NCT05852873. Registered on May 2023.
Keywords: COVID-19; Long COVID; Nirmatrelvir/ritonavir; Paxlovid; Post-COVID-19 condition; Prevention; Randomized controlled trial; SARS-CoV-2.