BACKGROUND: Post-exposure prophylaxis (PEP) is a well-established strategy for the prevention of infectious diseases, in which recently exposed people take a short course of medication to prevent infection . The primary objective of the COVID-19 Ring-based Prevention Trial with lopinavir/ritonavir (CORIPREV-LR) is to evaluate the efficacy of a 14-day course of oral lopinavir/ritonavir as PEP against COVID-19 among individuals with a high-risk exposure to a confirmed case .
METHODS: This is an open-label, multicenter , 1:1 cluster-randomized trial of LPV/r 800/200 mg twice daily for 14 days (intervention arm) versus no intervention (control arm), using an adaptive approach to sample size calculation . Participants will be individuals aged> 6 months with a high-risk exposure to a confirmed COVID-19 case within the past 7 days . A combination of remote and in-person study visits at days 1 , 7 , 14 , 35, and 90 includes comprehensive epidemiological, clinical, microbiologic, and serologic sampling . The primary outcome is microbiologically confirmed COVID-19 infection within 14 days after exposure, defined as a positive respiratory tract specimen for SARS-CoV-2 by polymerase chain reaction . Secondary outcomes include safety, symptomatic COVID-19, seropositivity, hospitalization, respiratory failure requiring ventilator support, mortality, psychological impact, and health-related quality of life. Additional analyses will examine the impact of LPV/r on these outcomes in the subset of participants who test positive for SARS-CoV-2 at baseline . To detect a relative risk reduction of 40% with 80% power at α = 0.05, assuming the secondary attack rate in ring members (p 0) = 15% , 5 contacts per case and intra-class correlation coefficient (ICC) = 0.05, we require 110 clusters per arm, or 220 clusters overall and approximately 1220 enrollees after accounting for 10% loss-to-follow-up . We will modify the sample size target after 60 clusters, based on preliminary estimates of p 0, ICC, and cluster size and consider switching to an alternative drug after interim analyses and as new data emerges . The primary analysis will be a generalized linear mixed model with logit link to estimate the effect of LPV/r on the probability of infection . Participants who test positive at baseline will be excluded from the primary analysis but will be maintained for additional analyses to examine the impact of LPV/r on early treatment .
DISCUSSION: Harnessing safe, existing drugs such as LPV/r as PEP could provide an important tool for control of the COVID-19 pandemic . Novel aspects of our design include the ring-based prevention approach, and the incorporation of remote strategies for conducting study visits and biospecimen collection .
TRIAL REGISTRATION: This trial was registered at www.ClinicalTrials.gov (NCT04321174) on March 25 , 2020.
MeSH: Antiviral Agents, therapeutic use, COVID-19, prevention & control, Drug Combinations, Hospitalization, Humans, Lopinavir, therapeutic use, Post-Exposure Prophylaxis, methods, Randomized Controlled Trials as Topic, Ritonavir, therapeutic use, SARS-CoV-2, Severity of Illness Index, Treatment Outcome
Index: COVID-19, Chemoprophylaxis, Cluster randomization, Lopinavir/ritonavir, Post-exposure prophylaxis, Protocol, Randomized controlled trial