PROTECT Trial: A cluster-randomized study with hydroxychloroquine versus observational support for prevention or early-phase treatment of Coronavirus disease (COVID-19): A structured summary of a study protocol for a randomized controlled trial
Oriana Nanni, Pierluigi Viale, Bernadette Vertogen, Claudia Lilli, Chiara Zingaretti, Caterina Donati, Carla Masini, Manuela Monti, Patrizia Serra, Roberto Vespignani, Veruska Grossi, Annibale Biggeri, Emanuela Scarpi, Francesca Galardi, Lucia Bertoni, Americo Colamartini, Fabio Falcini, Mattia Altini, Ilaria Massa, Raffaella Gaggeri, Giovanni Martinelli
Trials, doi:10.1186/s13063-020-04527-4
Objectives: Hydroxychloroquine has shown to have antiviral activity in vitro against coronaviruses, specifically SARS-CoV-2. It is believed to block virus infection by increasing endosomal pH required for virus cell fusion and glycosylation of viral surface proteins. In addition to its antiviral activity, hydroxychloroquine has an immune-modulating activity that may synergistically enhance its antiviral effect in vivo, making it a potentially promising drug for the prevention and the cure of SARS-CoV-19. However, randomized controlled trials are needed to assess whether it can be used safely to treat COVID-19 patients or to prevent infection. The main objective of the present study is to evaluate the efficacy of hydroxychloroquine for (I) the prevention of COVID-19 or related symptoms in SARS-CoV-2exposed subjects, such as as household members/contacts of COVID-19 patients and (II) the treatment of earlyphase asymptomatic or paucisymptomatic COVID-19 patients. Trial design: This is a controlled, open label, cluster-randomized, superiority trial with parallel group design. Subjects will be randomized either to receive hydroxychloroquine or to observation (2:1).
Supplementary information Supplementary information accompanies this paper at https://doi.org/10. 1186/s13063-020-04527-4. Additional file 1. Full Study Protocol. Additional file 2. SPIRIT 2013 Checklist: Recommended items to address in a clinical trial protocol and related documents. Authors' contributions G.M., P.V., O.N., A. B and M.A., were responsible for the study concept and trial design. B.V., C.L., C.Z., C.D., C.M., E.S., R.G., M.M., P. S and R.V. contributed to the study protocol drafting the final version of the protocol. All authors read and approved the present version of the manuscript for submission.
Funding IRST IRCCS is funding this trial and will have full oversight of the design of the study, collection, analysis, and interpretation of data and drafting of the manuscript.
Ethics approval and consent to participate On 20 th April 2020 this trial received the approval of the Ethics Committee (EC) of Istituto Nazionale per le Malattie Infettive Lazzaro Spallanzani-IRCCS, which is the national EC for COVID-19 trials. Informed consent will be obtained from participants prior to involvement in the trial. Given the extraordinary nature of the pandemic diffusion of COVID-19 and the safety measures set up to contain the spread of infection, it is not feasible to provide information to potentially eligible subjects through a face-to-face interview or to obtain informed consent signed in person by the subjects. Therefore, subjects will receive detailed information..
