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PreImplantation Trial of Histopathology In renal Allografts (PITHIA): a stepped-wedge cluster randomised controlled trial protocol
  1. John OO Ayorinde1,
  2. Dominic M Summers1,2,
  3. Laura Pankhurst2,
  4. Emma Laing3,
  5. Alison J Deary4,
  6. Karla Hemming5,
  7. Edward CF Wilson6,
  8. Victoria Bardsley7,
  9. Desley A Neil8,
  10. Gavin J Pettigrew1
  1. 1 Department of Surgery, University of Cambridge, Cambridge, UK
  2. 2 NHS Blood and Transplant, Watford, Hertfordshire, UK
  3. 3 Clinical Trials Unit, NHS Blood and Transplant, Cambridge, UK
  4. 4 NHS Blood and Transplant Clinical Studies Unit, Cambridge, UK
  5. 5 Department of Public Health, University of Birmingham, Birmingham, UK
  6. 6 Cambridge Centre for Health Services Research, University of Cambridge, Cambridge, UK
  7. 7 Department of Histopathology, University of Cambridge, Cambridge, UK
  8. 8 Department of Histopathology, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
  1. Correspondence to Gavin J Pettigrew; gjp25{at}cam.ac.uk

Abstract

Introduction Most potential kidney transplant donors in the UK are aged over 60 years, yet increasing donor age is associated with poorer graft survival and function. Urgent preimplantation kidney biopsy can identify chronic injury, and may aid selection of better ‘quality’ kidneys from this group. However, the impact of biopsy on transplant numbers remains unproven. The PreImplantation Trial of Histopathology In renal Allografts (PITHIA) study will assess whether the introduction of a national, 24 hours, digital histopathology service increases the number, and improves outcomes, of kidneys transplanted in the UK from older deceased donors.

Methods and analysis PITHIA is an open, multicentre, stepped-wedge cluster randomised study, involving all UK adult kidney transplant centres. At 4-monthly intervals, a group of 4–5 randomly selected clusters (transplant centres) will be given access to remote, urgent, digital histopathology (total intervention period, 24 months). The trial has two primary end points: it is powered for an 11% increase in the proportion of primary kidney offers from deceased donors aged over 60 years that are transplanted, and a 6 mL/min increase in the estimated glomerular filtration rate of recipients at 12 months post-transplant. This would equate to an additional 120 kidney transplants performed in the UK annually. Trial outcome data will be collected centrally via the UK Transplant Registry held by NHS Blood and Transplant (NHSBT) and will be analysed using mixed effects models allowing for clustering within centres and adjusting for secular trends. An accompanying economic evaluation will estimate the cost-effectiveness of the service to the National Health Service.

Ethics and dissemination The study has been given favourable ethical opinion by the Cambridge South Research Ethics Committee and is approved by the Health Research Authority. We will present our findings at key transplant meetings, publish results within 4 years of the trial commencing and support volunteers at renal patient groups to disseminate the trial outcome.

Trial registration number ISRCTN11708741; Pre-results.

  • renal transplantation
  • transplant surgery
  • histopathology
  • stepped-wedge
  • biopsy
  • health economics

This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See: https://creativecommons.org/licenses/by/4.0/.

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Footnotes

  • Patient consent for publication Not required.

  • Contributors GJP and DS conceived the study. JOOA wrote the original study protocol and revised it for publication with significant input from GJP, DS, DAN, KH, LP, ECFW, AJD and EL. GJP, DAN and DS initiated the study design and AJD, EL and JOOA helped with implementation and operational aspects. GJP is the primary grant holder. KH provided statistical expertise in clinical trial design and LP is conducting the primary statistical analysis. DN and VB provided oversight for the histopathological aspects of the study.

  • Funding This work was supported by the National Institute for Health Research: Research for Patient Benefit (RfPB) Programme (PB-PG-1215-20033). The Digital Histopathology Scanners were donated by Addenbrooke’s Charitable Trust.

  • Competing interests None declared.

  • Ethics approval The study has been given a favourable ethical opinion by the Cambridge South Research Ethics Committee and has received approval by the Health Research Authority on the basis of the full study protocol.

  • Provenance and peer review Not commissioned; peer reviewed for ethical and funding approval prior to submission.

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