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

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 SA...

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Main Authors: François Chappuis, Idris Guessous, Thomas Perneger, Manuel Battegay, Laurent Kaiser, Mikaela Smit, Frederique Jacquerioz, Annalisa Marinosci, Giovanni Jacopo Nicoletti, Silvio Ragozzino, Diego O Andrey, Dan Lebowitz, Benjamin Meyer, Herve Spechbach, Julien Salamun, Moritz Back, Carla Schaubhut, Simon Fuchs, Laurent Decosterd, Niklaus D Labhardt
Format: Article
Language:English
Published: BMJ Publishing Group 2020-11-01
Series:BMJ Open
Online Access:https://bmjopen.bmj.com/content/10/11/e040110.full
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author François Chappuis
Idris Guessous
Thomas Perneger
Manuel Battegay
Laurent Kaiser
Mikaela Smit
Frederique Jacquerioz
Annalisa Marinosci
Giovanni Jacopo Nicoletti
Silvio Ragozzino
Diego O Andrey
Dan Lebowitz
Benjamin Meyer
Herve Spechbach
Julien Salamun
Moritz Back
Carla Schaubhut
Simon Fuchs
Laurent Decosterd
Niklaus D Labhardt
author_facet François Chappuis
Idris Guessous
Thomas Perneger
Manuel Battegay
Laurent Kaiser
Mikaela Smit
Frederique Jacquerioz
Annalisa Marinosci
Giovanni Jacopo Nicoletti
Silvio Ragozzino
Diego O Andrey
Dan Lebowitz
Benjamin Meyer
Herve Spechbach
Julien Salamun
Moritz Back
Carla Schaubhut
Simon Fuchs
Laurent Decosterd
Niklaus D Labhardt
author_sort François Chappuis
collection DOAJ
description 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.
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spelling doaj-art-8d97a7d7d47d435ab1a87d68fdbcfb5b2025-08-20T01:52:45ZengBMJ Publishing GroupBMJ Open2044-60552020-11-01101110.1136/bmjopen-2020-040110Efficacy of pragmatic same-day ring prophylaxis for adult individuals exposed to SARS-CoV-2 in Switzerland (COPEP): protocol of an open-label cluster randomised trialFrançois Chappuis0Idris Guessous1Thomas Perneger2Manuel Battegay3Laurent Kaiser4Mikaela Smit5Frederique Jacquerioz6Annalisa Marinosci7Giovanni Jacopo Nicoletti8Silvio Ragozzino9Diego O Andrey10Dan Lebowitz11Benjamin Meyer12Herve Spechbach13Julien Salamun14Moritz Back15Carla Schaubhut16Simon Fuchs17Laurent Decosterd18Niklaus D Labhardt19medical doctor1 Division of Primary Care Medicine, Geneva University Hospitals, Geneva, SwitzerlandDivision of Clinical Epidemiology, Geneva University Hospitals, Geneva, Switzerland3 Clinical Research, University of Basel, Basel, SwitzerlandDepartment of Medicine, Division of Infectious Diseases, University Hospital Geneva, Geneva, SwitzerlandFaculty of Medicine, University of Geneva, Geneva, SwitzerlandDivision of Tropical and Humanitarian Medicine, Geneva University Hospitals, Geneva, SwitzerlandHIV Unit, Geneva University Hospitals, Geneva, SwitzerlandDepartment of Medicine, Swiss Tropical and Public Health Institute, Basel, SwitzerlandDepartment of Infectious Diseases and Hospital Epidemiology, University of Basel, Basel, SwitzerlandHIV Unit, Geneva University Hospitals, Geneva, SwitzerlandInfection Control Programme, Geneva University Hospitals, Geneva, SwitzerlandCentre for Vaccinology, Department of Pathology and Immunology, University of Geneva, Geneva, Switzerland1 Division of Primary Care Medicine, Geneva University Hospitals, Geneva, Switzerland1 Division of Primary Care Medicine, Geneva University Hospitals, Geneva, SwitzerlandGesundheitsdepartement, Canton of Basel City, Basel, SwitzerlandGesundheitsdepartement, Canton of Basel City, Basel, SwitzerlandGesundheitsdepartement, Canton of Basel City, Basel, SwitzerlandLaboratory of Clinical Pharmacology, University of Lausanne, Lausanne, SwitzerlandDepartment of Medicine, Swiss Tropical and Public Health Institute, Basel, SwitzerlandIntroduction 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.https://bmjopen.bmj.com/content/10/11/e040110.full
spellingShingle François Chappuis
Idris Guessous
Thomas Perneger
Manuel Battegay
Laurent Kaiser
Mikaela Smit
Frederique Jacquerioz
Annalisa Marinosci
Giovanni Jacopo Nicoletti
Silvio Ragozzino
Diego O Andrey
Dan Lebowitz
Benjamin Meyer
Herve Spechbach
Julien Salamun
Moritz Back
Carla Schaubhut
Simon Fuchs
Laurent Decosterd
Niklaus D Labhardt
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
BMJ Open
title 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
url https://bmjopen.bmj.com/content/10/11/e040110.full
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