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

• Published in: Current controlled trials in cardiovascular medicine 2020-07, Vol.21 (1), p.689-4, Article 689
• Main Authors: Nanni, Oriana, Viale, Pierluigi, Vertogen, Bernadette, Lilli, Claudia, Zingaretti, Chiara, Donati, Caterina, Masini, Carla, Monti, Manuela, Serra, Patrizia, Vespignani, Roberto, Grossi, Veruska, Biggeri, Annibale, Scarpi, Emanuela, Galardi, Francesca, Bertoni, Lucia, Colamartini, Americo, Falcini, Fabio, Altini, Mattia, Massa, Ilaria, Gaggeri, Raffaella, Martinelli, Giovanni
• Format: Article
• Language: English
• Subjects: Antiviral drugs; Asymptomatic; Cardiac arrhythmia; Clinical trials; Cluster Analysis; Coronaviruses; COVID-19; COVID-19 - prevention & control; COVID-19 Drug Treatment; Disease prevention; Dosage and administration; Drug dosages; Female; Households; Humans; Hydroxychloroquine; Hydroxychloroquine - therapeutic use; Infections; Male; Management; Methods; Pandemics - prevention & control; Patient Reported Outcome Measures; Patients; Prevention; Prophylaxis; Protocol; Randomized controlled clinical trial; Randomized Controlled Trials as Topic; SARS-CoV-2; Severe acute respiratory syndrome coronavirus 2; Study Protocol; Telemedicine
• ISSN: 1745-6215; 1745-6215
• DOI: 10.1186/s13063-020-04527-4

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-2-exposed subjects, such as as household members/contacts of COVID-19 patients and (II) the treatment of early-phase asymptomatic or paucisymptomatic COVID-19 patients. 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). SARS-CoV-2-exposed subjects, including household members and/or contacts of COVID-19 patients and healthcare professionals (Group 1) or patients with COVID-19 (positive PCR test on a rhinopharyngeal or oropharyngeal swab for SARS-CoV-2), asymptomatic or paucisymptomatic in home situations who are not undergoing treatment with any anti COVID-19 medication (Group 2), will be enrolled. Paucisymptomatic patients are defined as patients with a low number of mild symptoms. All subjects must be aged ≥18 years, male or female, must be willing and able to give informed consent and must not have any contraindications to take hydroxychloroquine (intolerance or previous toxicity for hydroxychloroquine/chloroquine, bradycardia or reduction in heart rhythm with arrhythmia, ischemic heart disease, retinopathy, congestive heart failure with use of diuretics, favism or glucose-6-phosphate dehydrogenase (G6PD) deficiency, diabetes type 1, major comorbidities such as advanced chronic kidney disease or dialysis therapy, known history of ventricular arrhythmia, any oncologic/hematologic malignancy, severe neurological and mental illness, current use of medications with known significant drug-drug interactions, and known prolonged QT syndrome or current use of drugs with known QT prolongation). The study is monocentric and will be conducted at I