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Protocol for a double-blind placebo-controlled trial to evaluate the efficacy of probiotics in reducing antibiotics for infection in care home residents: the Probiotics to Reduce Infections iN CarE home reSidentS (PRINCESS) trial
  1. Eleri Owen-Jones1,
  2. Rachel Lowe1,
  3. Mark Lown2,
  4. David Gillespie1,
  5. Katy Addison1,
  6. Tony Bayer3,
  7. Philip C Calder4,5,
  8. Jane Davies1,
  9. Mina Davoudianfar6,
  10. James Downs7,
  11. Alison Edwards1,
  12. Nick A Francis3,
  13. Richard Fuller2,
  14. Richard Hobbs6,
  15. Kerenza Hood1,
  16. Mandy Lau1,
  17. Paul Little2,
  18. Michael Moore2,
  19. Victoria Shepherd3,
  20. Helen Stanton1,
  21. Alun Toghill7,
  22. Mandy Wootton8,
  23. Chris C Butler6
  1. 1 Centre for Trials Research, Cardiff University, Cardiff, UK
  2. 2 Primary Care and Population Sciences, University of Southampton, Aldermoor Health Centre, Southampton, UK
  3. 3 Division of Population Medicine, School of Medicine, Neuadd Meirionnydd, Cardiff University, Cardiff, UK
  4. 4 Human Development & Health, Faculty of Medicine, University of Southampton, Southampton, UK
  5. 5 NIHR Southampton Biomedical Research Centre, University of Southampton NHS Foundation Trust and University of Southampton, Southampton, UK
  6. 6 Clinical Trials Unit, Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK
  7. 7 Lay Representative, Cardiff, UK
  8. 8 Specialist Antimicrobial Chemotherapy Unit, Public Health Wales Microbiology Cardiff, University Hospital of Wales, Cardiff, UK
  1. Correspondence to Dr Eleri Owen-Jones; Owen-JonesCE{at}cardiff.ac.uk

Abstract

Introduction Care home residents are at increased risk of infections and antibiotic prescription. Reduced antibiotic use from fewer infections would improve quality of life. The Probiotics to Reduce Infections iN CarE home reSidentS (PRINCESS) trial aims to determine the efficacy and investigate mechanisms of daily probiotics on antibiotic use and incidence of infections in care home residents.

Methods and analysis PRINCESS is a double-blind, individually randomised, placebo-controlled trial that will assess the effect of a daily oral probiotic combination of Lactobacillus rhamnosus, GG (LGG) and Bifidobacterium animalis subsp. lactis, BB-12 (BB-12) on cumulative antibiotic administration days (CAADs) (primary outcome) for infection in up to 330 care home residents aged ≥65 years over up to 12 months. Secondary outcomes include: Infection: Total number of days of antibiotic administration for each infection type (respiratory tract infection, urinary tract infection, gastrointestinal infection, unexplained fever and other); number, site, duration of infection; estimation of incidence and duration of diarrhoea and antibiotic-associated diarrhoea; Stool microbiology: Clostridium difficile infection; Gram-negative Enterobacteriaceae and vancomycin-resistant enterococci; LGG and BB-12. Oral microbiology: Candida spp. Health and well-being: Self and/or proxy health-related quality of life EQ5D (5 L); self-and/or proxy-reported ICEpop CAPability measure for older people. Hospitalisations: number and duration of all-cause hospital stays. Mortality: deaths. Mechanistic immunology outcomes: influenza vaccine efficacy (haemagglutination inhibition assay and antibody titres); full blood count and immune cell phenotypes, plasma cytokines and chemokines; cytokine and chemokine response in whole blood stimulated ex vivo by toll-like receptor 2 and 4 agonists; monocyte and neutrophil phagocytosis of Escherichia coli; serum vitamin D.

Ethics and dissemination Ethics approval is from the Wales Research Ethics Committee 3. Findings will be disseminated through peer-reviewed journals and conferences; results will be of interest to patient and policy stakeholders.

Trial registration number ISRCTN16392920; Pre-results.

  • probiotics
  • care home
  • flu
  • infection
  • antibiotic use
  • antibiotic resistance

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Footnotes

  • Contributors CCB is the Chief Investigator of this trial. CCB led the development of the research question, study design, obtaining the funding and implementation of the study protocol, along with TB, PCC, JDo, NAF, RF, DG, RH, KH, PL, ML, MM, VS, AT and MW. EO-J is the Trial Manager and RL the Senior Trial Manager who coordinated the operational delivery of the study protocol and recruitment. JD and AE provide research nurse support. DG and MLau are the trial statisticians. MD is the Trial Manager. KA and HS are the data managers. All authors listed provided critical review and final approval of the manuscript.

  • Funding This work was supported by the Efficacy and Mechanism Evaluation programme, which is funded by the MRC and NIHR, with contributions from CSO in Scotland, HCRW in Wales and the HSC R&D, Public Health Agency in Northern Ireland. This project is managed by the NIHR Evaluation, Trials and Studies Coordination Centre (NETSCC) (Efficacy and Mechanism Evaluation (EME), grant number 13/95/10 – Probiotics to Reduce Infections iN CarE home reSidentS (PRINCESS)). The views expressed in this publication are those of the author(s) and not necessarily those of the MRC, NHS, the National Institute for Health Research or the Department of Health. Cardiff University, Research and Innovation Services Department, Contracts Team, Cardiff University, 30-36 Newport Road, Cardiff, CF24 0DE (SPON1426-15).

  • Competing interests PCC reports grants from National Institute for Health Research, grants from EME Programme funded by NIHR / MRC. During the conduct of the study PCC receives personal fees from Christian Hansen, and non-financial support from Christian Hansen outside the submitted work.

  • Ethics approval The Wales REC 3 has approved the study (15/WA/0306) on 13 November 2015.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Patient consent for publication Not required.

  • Patient and public involvement The authors would like to acknowledge the contribution of Alun Toghill and James Downs as the public and patient involvement representatives on the Trial Management Group.

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