Efficacy of same day chemoprophylaxis for exposed asymptomatic individuals exposed to SARS-CoV-2 in Switzerland: a pragmatic open-label cluster randomized trial (COPEP-trial)

Background: Severe Acute Respiratory Coronavirus 2 (SARS-CoV-2) is a novel coronavirus strain that was declared a pandemic by the World Health Organization on 11th March 2020. The world is now scrambling to identify effective pharmacological candidates for its prevention and treatment. The availability of simple and effective post-exposure prophylaxis (PEP) to prevent either SARS-CoV-2 infection and/or resulting clinical Coronavirus Disease (COVID-19) will play a crucial role both for the rapid containment and to protect at risk individuals including front-line health care workers now and in future outbreaks. Objectives We propose to assess the efficacy, safety and acceptability of same-day LPV/r-based and HCQ-based PEP compared to standard of care for asymptomatic individuals exposed to individuals diagnosed with SARS-CoV-2 in a category B open-label cluster randomized clinical trial. The study has two co-primary endpoints; 14-day incidence of clinical COVID-19 and 14-day incidence of PCR-confirmed SARS-CoV-2. Method: Participants will be screened if they had a close contact of newly diagnosed SARS-CoV-2 index cases as early as possible and randomized no later than 48 hours after the document contact. Adults without fever or respiratory symptoms will be enrolled across two sites, Geneva and Basel. During baseline visit, naso-pharyngeal swab, SARS-CoV-2 serology (rapid test) and a clinical assessment will be performed and individuals will be randomized by household 1:1:1 to either LPV/r 400/100 mg twice daily for 5 days versus a single dose of 800mg HCQ versus no treatment. Individuals will be asked to record daily their temperature and complete a online symptoms and adverse events questionnaire during the 14 days of follow-up. Participants who record COVID-19 symptoms will undergo clinical assessment and a naso-pharyngeal swab to confirm/exclude SARS-CoV-2 infection, and if found positive will be provided with appropriate care. Follow-up visit at Day 14 will include a naso-pharyngeal swab and completion of questionnaires on adherence and acceptability of the PEP intervention.Endpoints: This trial has two co-primary endpoints: a) 14-day incidence of COVID-19 in individuals exposed to SARS-CoV-2 who are asymptomatic at baseline (intention-to-treat (ITT) analysis)b) 14-day incidence of SARS-CoV-2 in individuals exposed to SARS-CoV-2 who are asymptomatic and PCR-confirmed SARS-CoV-2 negative at baseline (modified ITT)Secondary endpoints:a) severity of clinical COVID-19 (0- asymptomatic or with mild disease; 1 - hospitalized or died)b) adverse events c) adherence to and acceptance of PEPStudy impact and importance: COVID-19 generates intense pressure on health systems across the world, with the sudden and uncontrolled influx of severe cases causing depletion of all hospital-based resources. Meanwhile, asymptomatic SARS-CoV-2 infections fuel the pandemic. A simple and effective PEP strategy, that can be prescribed the same day with limited laboratory exams, will help contain both the current pandemic and future COVID-19 outbreaks. Even if effective vaccination and treatment become available, PEP will play an important role in safeguarding individuals at highest risk, including front-line health care workers, and will be crucial for rapid containment of future outbreaks. The PEP candidates we are proposing to investigate are cheap, safe and globally available, including in Switzerland. This makes them particularly attractive PEP candidates worldwide, including settings where health systems are fragile and the scarcity of tertiary care facilities, intensive care bed and ventilators cause concern in face of COVID-19.