tetano
Editor, Senior Moderator
BMJ Open
. 2020 Nov 12;10(11):e040110.
doi: 10.1136/bmjopen-2020-040110.
Efficacy of pragmatic same-day ring prophylaxis for adult individuals exposed to SARS-CoV-2 in Switzerland (COPEP): protocol of an open-label cluster randomised trial
Mikaela Smit[SUP] 1 2 [/SUP], Annalisa Marinosci[SUP] 3 [/SUP], Giovanni Jacopo Nicoletti[SUP] 4 [/SUP], Thomas Perneger[SUP] 2 5 [/SUP], Silvio Ragozzino[SUP] 6 [/SUP], Diego O Andrey[SUP] 3 2 7 [/SUP], Marcel Stoeckle[SUP] 6 [/SUP], Frederique Jacquerioz[SUP] 8 [/SUP], Dan Lebowitz[SUP] 9 10 [/SUP], Thomas Agoritsas[SUP] 2 11 12 [/SUP], Benjamin Meyer[SUP] 13 [/SUP], Herve Spechbach[SUP] 8 [/SUP], Julien Salamun[SUP] 8 [/SUP], Moritz Back[SUP] 14 [/SUP], Carla Schaubhut[SUP] 14 [/SUP], Simon Fuchs[SUP] 14 [/SUP], Laurent Decosterd[SUP] 15 [/SUP], Manuel Battegay[SUP] 6 [/SUP], Idris Guessous[SUP] 8 [/SUP], Fran?ois Chappuis[SUP] 8 [/SUP], Laurent Kaiser[SUP] 16 17 [/SUP], Niklaus D Labhardt[SUP] 4 6 [/SUP], Alexandra Calmy[SUP] 3 2 [/SUP]
Affiliations
Abstract
Introduction: Lopinavir/ritonavir (LPV/r) has been proposed as repurposed drugs for pre-exposure and postexposure prophylaxis as well as therapy of COVID-19. Coronavirus postexposure prophylaxis (COPEP) trial aims at assessing their efficacy as postexposure ring-prophylaxis among adults exposed to SARS-CoV-2.
Methods and analysis: COPEP is a two-arm open-label cluster-randomised trial conducted in three cantons of Switzerland. Asymptomatic contacts (≥16 years) of individuals diagnosed with COVID-19 will be randomised (2:1) to either LPV/r (400 mg/100 mg two times per day) for 5 days, or a standard of care arm (no treatment). Asymptomatic individuals may be either SARS-CoV-2 positive or negative. Contacts living in the single household will form a cluster and will be randomised into the same arm. All participants will be followed-up for 21 days and undergo daily monitoring for COVID-19 symptoms. The primary endpoint is 21-day incidence of laboratory-confirmed COVID-19 with ≥1 compatible symptom, analysed in an intention-to-treat (ITT) analysis. The secondary endpoints include the 21-day incidence of COVID-19 as well as SARS-CoV-2 infection in a modified ITT analysis, excluding participants who had a positive SARS-CoV-2 RT-PCR from oropharyngeal swab and/or a positive SARS-CoV-2 IgG serology at baseline. Assuming a 21-day incidence for COVID-19 of 20% among contacts without postexposure chemoprophylaxis, to detect a relative risk reduction of 60% (ie, translating in an absolute reduction from 20% to 8%), with a power of 80%, an alpha of 5%. Accounting for design effect of cluster design of circa 1.1, we plan to enrol 200 participants to the LPV/r arm and 100 to the standard of care arm, 300 participants in total.
Ethics and dissemination: Ethics approval has been granted by the Commission Cantonale d'Ethique de la Recherche, Ethikkommission Nordwest- und Zentralschweiz and Comitato Etico Cantonale (ref 2020-00864) and Swissmedic (2020DR3056). Results from this trial will be disseminated via journal articles and presentations at national and international conferences.
Trial registration number: Clinicaltrials.gov Registry (NCT04364022); Swiss National Clinical Trial Portal Registry (SNCTP 000003732).
Registered report identifier: CCER 2020-0864.
Keywords: COVID-19; clinical trials; epidemiology; infectious diseases; preventive medicine.
. 2020 Nov 12;10(11):e040110.
doi: 10.1136/bmjopen-2020-040110.
Efficacy of pragmatic same-day ring prophylaxis for adult individuals exposed to SARS-CoV-2 in Switzerland (COPEP): protocol of an open-label cluster randomised trial
Mikaela Smit[SUP] 1 2 [/SUP], Annalisa Marinosci[SUP] 3 [/SUP], Giovanni Jacopo Nicoletti[SUP] 4 [/SUP], Thomas Perneger[SUP] 2 5 [/SUP], Silvio Ragozzino[SUP] 6 [/SUP], Diego O Andrey[SUP] 3 2 7 [/SUP], Marcel Stoeckle[SUP] 6 [/SUP], Frederique Jacquerioz[SUP] 8 [/SUP], Dan Lebowitz[SUP] 9 10 [/SUP], Thomas Agoritsas[SUP] 2 11 12 [/SUP], Benjamin Meyer[SUP] 13 [/SUP], Herve Spechbach[SUP] 8 [/SUP], Julien Salamun[SUP] 8 [/SUP], Moritz Back[SUP] 14 [/SUP], Carla Schaubhut[SUP] 14 [/SUP], Simon Fuchs[SUP] 14 [/SUP], Laurent Decosterd[SUP] 15 [/SUP], Manuel Battegay[SUP] 6 [/SUP], Idris Guessous[SUP] 8 [/SUP], Fran?ois Chappuis[SUP] 8 [/SUP], Laurent Kaiser[SUP] 16 17 [/SUP], Niklaus D Labhardt[SUP] 4 6 [/SUP], Alexandra Calmy[SUP] 3 2 [/SUP]
Affiliations
- PMID: 33184083
- DOI: 10.1136/bmjopen-2020-040110
Abstract
Introduction: Lopinavir/ritonavir (LPV/r) has been proposed as repurposed drugs for pre-exposure and postexposure prophylaxis as well as therapy of COVID-19. Coronavirus postexposure prophylaxis (COPEP) trial aims at assessing their efficacy as postexposure ring-prophylaxis among adults exposed to SARS-CoV-2.
Methods and analysis: COPEP is a two-arm open-label cluster-randomised trial conducted in three cantons of Switzerland. Asymptomatic contacts (≥16 years) of individuals diagnosed with COVID-19 will be randomised (2:1) to either LPV/r (400 mg/100 mg two times per day) for 5 days, or a standard of care arm (no treatment). Asymptomatic individuals may be either SARS-CoV-2 positive or negative. Contacts living in the single household will form a cluster and will be randomised into the same arm. All participants will be followed-up for 21 days and undergo daily monitoring for COVID-19 symptoms. The primary endpoint is 21-day incidence of laboratory-confirmed COVID-19 with ≥1 compatible symptom, analysed in an intention-to-treat (ITT) analysis. The secondary endpoints include the 21-day incidence of COVID-19 as well as SARS-CoV-2 infection in a modified ITT analysis, excluding participants who had a positive SARS-CoV-2 RT-PCR from oropharyngeal swab and/or a positive SARS-CoV-2 IgG serology at baseline. Assuming a 21-day incidence for COVID-19 of 20% among contacts without postexposure chemoprophylaxis, to detect a relative risk reduction of 60% (ie, translating in an absolute reduction from 20% to 8%), with a power of 80%, an alpha of 5%. Accounting for design effect of cluster design of circa 1.1, we plan to enrol 200 participants to the LPV/r arm and 100 to the standard of care arm, 300 participants in total.
Ethics and dissemination: Ethics approval has been granted by the Commission Cantonale d'Ethique de la Recherche, Ethikkommission Nordwest- und Zentralschweiz and Comitato Etico Cantonale (ref 2020-00864) and Swissmedic (2020DR3056). Results from this trial will be disseminated via journal articles and presentations at national and international conferences.
Trial registration number: Clinicaltrials.gov Registry (NCT04364022); Swiss National Clinical Trial Portal Registry (SNCTP 000003732).
Registered report identifier: CCER 2020-0864.
Keywords: COVID-19; clinical trials; epidemiology; infectious diseases; preventive medicine.