@article{Ball_J-2025_200451,
title = {Lessons from the PROTECT-CH COVID-19 platform trial in care homes},
author = {Ball, J. and Boyd, M. and Gage, H. and Glover, M. and Godfrey, M. and Guthrie, B. and Hewitt, J. and Howard, R. and Jaki, T. and Juszczak, E. and Lasserson, D. and Leighton, P. and Leyland, V. and Lim, W. and Logan, P. and Meakin, G. and Montgomery, A. and Ogollah, R. and Passmore, P. and Quinlan, P. and Rick, C. and Royal, S. and Shenkin, S. and Upton, C. and Gordon, A. and Bath, P.},
month = {apr},
year = {2025},
abstract = {Background: Coronavirus disease-2019 (COVID-19) was associated with significant mortality and morbidity in care homes in 2020–21. Repurposed antiviral drugs might reduce morbidity and mortality through reducing viral transmission, infection, replication and inflammation. We aimed to compare the safety and efficacy of potential antiviral drugs in care home residents. Methods: We designed a cluster-randomised open-label blinded-endpoint platform-trial to test drugs in a post-exposure prophylaxis paradigm. Participants aged 65+ years from UK care homes with or without nursing, were eligible for participation. Care homes were to be allocated at random by computer to administer 42 days of antiviral agent (ciclesonide or niclosamide) plus standard care versus standard care to residents. The primary outcome at 60 days after randomisation comprised the most serious outcome defined as all-cause mortality, all-cause hospitalisation, SARS-CoV-2 infection or no infection. Analysis would be by intention-to-treat using ordinal logistic regression. Other outcomes included individual components of the primary outcome, transmission, plus health economic and process evaluation outcomes. The planned sample size was 300 care homes corresponding to 9,600 residents. With ~40% of care homes predicted to develop an outbreak during the trial, we needed to recruit 750 homes/24,000 residents. Results: We initiated the trial including protocol, approvals, insurance, website, database, data algorithms, intervention selection and training materials. We built a network of principal investigators and staff (91) and care homes (299) to support the trial. However, we never contracted care homes or general practitioners (GPs) since the trial was stopped in September 2021, as vaccination in care homes had significantly reduced infections. Multiple delays significantly delayed the start date: i) reduced prioritisation of pandemic trials in 2021; ii) cumbersome mechanisms for choosing the investigational medicinal products (IMPs); iii) contracting between NIHR and the IMP manufacturers; iv) publicising the IMPs; v) identification of sufficient numbers of care homes; vi) identification and contracting with several thousand GPs; vii) limited research nurse availability; and viii) identification of adequate insurance to cover care homes for research. Generic challenges including working across the four home nations with their different structures and regulations. Limitations: The feasibility of contracting between the sponsor and the PIs, GPs and care homes; screening, consent and treatment of care home residents; data acquisition and the potential benefit of post-exposure prophylaxis were never tested. Conclusions: The success of vaccination meant that the role of post-exposure prophylaxis of COVID-19 in care home residents was not tested. Significant progress was made in developing the infrastructure and expertise necessary for a large scale Clinical Trial of IMPs in UK care homes. Future work: The role of post-exposure prophylaxis of COVID-19 in care home residents remains undefined. Significant logistical barriers to conducting research in care homes need to be removed urgently before future studies are possible. Further work is required to develop the infrastructure for clinical trials of investigational medicinal products in care homes. Serious consideration should be given to building and then hibernating a pandemic-ready platform trial suitable for care home research. Registration: EudraCT 2021-000185-15. Funding: This project was funded by the National Institute for Health and Care Research (NIHR) XP programme (NIHR133443) and will be published in XXX Journal: Vol. XX, No. XX. See the NIHR Journals Library website for further project information.},
journal = {Health Technology Assessment},
publisher = {National Institute for Health and Care Research},
url = {https://doi.org/10.3310/MTRS8833},
}
