Prophylactic Treatment of COVID-19 in Care Homes Trial (PROTECT-CH)

Abstract

AbstractBackgroundCoronavirus disease 2019 (COVID-19) is associated with significant mortality and morbidity in care homes. Novel or repurposed antiviral drugs may reduce infection and disease severity through reducing viral replication and inflammation.ObjectiveTo compare the safety and efficacy of antiviral agents (ciclesonide, niclosamide) for preventing SARS-CoV-2 infection and COVID-19 severity in care home residents.DesignCluster-randomised open-label blinded endpoint platform clinical trial testing antiviral agents in a post-exposure prophylaxis paradigm.SettingCare homes across all four United Kingdom member countries.ParticipantsCare home residents 65 years of age or older.InterventionsCare homes were to be allocated at random by computer to 42 days of antiviral agent plus standard care versus standard of care and followed for 60 days after randomisation.Main outcome measuresThe primary four-level ordered categorical outcome with participants classified according to the most serious of all-cause mortality, all-cause hospitalisation, SARS-CoV-2 infection and no infection. Analysis using ordinal logistic regression was by intention to treat. Other outcomes included the components of the primary outcome and transmission.ResultsDelays in contracting between NIHR and the manufacturers of potential antiviral agents significantly delayed any potential start date. Having set up the trial (protocol, approvals, insurance, website, database, routine data algorithms, training materials), the trial was stopped in September 2021 prior to contracting of care homes and general practitioners in view of the success of vaccination in care homes with significantly reduced infections, hospitalisations and deaths. As a result, the sample size target (based on COVID-19 rates and deaths occurring in February-June 2020) became unfeasible.LimitationsCare home residents were not approached about the trial and so were not consented and did not receive treatment. Hence, the feasibility of screening, consent, treatment and data acquisition, and potential benefit of post exposure prophylaxis were never tested. Further, contracting between the University of Nottingham and the PIs, GPs and care homes was not completed, so the feasibility of contracting with all the different groups at the scale needed was not tested.ConclusionsThe role of post exposure prophylaxis of COVID-19 in care home residents was not tested because of changes in COVID-19 incidence, prevalence and virulence as a consequence of the vaccination programme that rendered the study unfeasible. Significant progress was made in describing and developing the infrastructure necessary for a large scale Clinical Trial of Investigational Medicinal Products in care homes in all four UK nations.Future workThe role of post-exposure prophylaxis of COVID-19 in care home residents remains to be defined. Significant logistical barriers to conducting research in care homes during a pandemic need to be removed before such studies are possible in the required short timescale.