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

Background Coronavirus 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. Objective To compare the safety and efficacy of antiviral agents (ciclesonide, niclosamide) for preventing SARS-CoV-2 infection and COVID-19 severity in care home residents. Design Cluster-randomised open-label blinded endpoint platform clinical trial testing antiviral agents in a post-exposure prophylaxis paradigm. Setting Care homes across all four United Kingdom member countries. Participants Care home residents 65 years of age or older. Interventions Care 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 measures The 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. Results Delays 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. Limitations Care 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. Conclusions The 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 work The 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. ### Competing Interest Statement 1.Philip M Bath: Grants from British Heart Foundation and NIHR Health Technology Appraisal programme during the conduct of the study; personal fees from DiaMedica and Phagenesis outside the submitted work. 2.Jonathan Ball: Reports no competing interests. 3.Matthew Boyd: Personal fees from Delphi Healthcare outside the submitted work. 4.Heather Gage: Reports no competing interests. 5.Matthew Glover: Reports no competing interests. 6.Maureen Godfrey: Reports no competing interests. 7.Bruce Guthrie: Grants from NIHR, Medical Research Council, Legal and General PLC, and Chief Scientist Office outside the submitted work; and is a member of the SAGE Social Care Workgroup. 8.Jonathan Hewitt: Funding from Health and Social Care Research Wales (HSCRW) during the grant. 9.Robert Howard: Grants from NIHR Health Technology Appraisal, Medical Research Council and NIHR UCLH Biomedical Research Centre. 10.Thomas Jaki: Grants from NIHR and MRC during conduct of the study. 11.Edmund Juszczak: Grants from NIHR during conduct of the study. 12.Dan Lasserson: Grants from NIHR HTA Clinical Evaluation and Trials, NIHR Policy Research Programme, NIHR RfPB, NIHR ARC and MIC funding schemes, institutional funding for quality improvement studies from Vifor Pharma outside of the current work. 13.Paul Leighton: Grants from NIHR during conduct of the study. 14.Val Leyland: Reports no competing interests. 15.Wei Shen Lim: Grants from NIHR and my institution has received unrestricted investigator-initiated research funding from Pfizer for a study in which WSL is CI, during the conduct of the study. 16.Pip Logan: Grants from NIHR Health Technology Appraisal, NIHR RfPB. 17.Garry Meakin: Reports no competing interests. 18.Alan A Montgomery: Member NIHR HTA Clinical Evaluation and Trials Funding Committee; grants from NIHR during conduct of the study. 19.Reuben Ogollah: Grants from NIHR during conduct of the study. 20.Peter Passmore: Reports no competing interests. 21.Phil Quinlan: Reports no competing interests. 22.Caroline Rick: Grants from NIHR during conduct of the study. 23.Simon Royal: Reports no competing interests. 24.Susan D Shenkin: Grants from British Geriatrics Society, NIHR, Edinburgh Lothian Health Foundation, Marie Curie and Chief Scientist Office during the conduct of the study. 25.Clare Upton: Reports no competing interests. 26.Adam L Gordon: Grants from NIHR, Asthma UK, the British Lung Foundation, the Wellcome Trust and British Geriatrics Society during the conduct of this research; and is a member of the SAGE Social Care Workgroup. ### Clinical Trial EudraCT: 2021-000185-15; WHO UTN: U1111-1265-4068 ### Clinical Protocols ### Funding Statement This study was funded by the National Institute for Health Research Cross Programme (XP). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: South Central - Oxford A Research Ethics Committee gave ethical approval for this work (21/SC/0166, dated 17 May 2021). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes The trial never recruited patients so no data are available.