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Can a combined screening/treatment programme prevent premature failure of renal transplants due to chronic rejection in patients with HLA antibodies: study protocol for the multicentre randomised controlled OuTSMART trial

Dorling, A; Rebollo-Mesa, I; Hilton, R; Peacock, JL; Vaughan, R; Gardner, L; Danzi, G; ... Murphy, C; + view all (2014) Can a combined screening/treatment programme prevent premature failure of renal transplants due to chronic rejection in patients with HLA antibodies: study protocol for the multicentre randomised controlled OuTSMART trial. Trials , 15 (30) 10.1186/1745-6215-15-30. Green open access

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Can a combined screening/treatment programme prevent premature failure of renal transplants due to chronic rejection in patients with HLA antibodies: study protocol for the multicentre randomised controlled OuTSMART trial.pdf - Published Version

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Abstract

BACKGROUND: Renal transplantation is the best treatment for kidney failure, in terms of length and quality of life and cost-effectiveness. However, most transplants fail after 10 to 12 years, consigning patients back onto dialysis. Damage by the immune system accounts for approximately 50% of failing transplants and it is possible to identify patients at risk by screening for the presence of antibodies against human leukocyte antigens. However, it is not clear how best to treat patients with antibodies. This trial will test a combined screening and treatment protocol in renal transplant recipients. METHODS/DESIGN: Recipients >1 year post-transplantation, aged 18 to 70 with an estimated glomerular filtration rate >30 mL/min will be randomly allocated to blinded or unblinded screening arms, before being screened for the presence of antibodies. In the unblinded arm, test results will be revealed. Those with antibodies will have biomarker-led care, consisting of a change in their anti-rejection drugs to prednisone, tacrolimus and mycophenolate mofetil. In the blinded arm, screening results will be double blinded and all recruits will remain on current therapy (standard care). In both arms, those without antibodies will be retested every 8 months for 3 years. The primary outcome is the 3-year kidney failure rate for the antibody-positive recruits, as measured by initiation of long-term dialysis or re-transplantation, predicted to be approximately 20% in the standard care group but <10% in biomarker-led care. The secondary outcomes include the rate of transplant dysfunction, incidence of infection, cancer and diabetes mellitus, an analysis of adherence with medication and a health economic analysis of the combined screening and treatment protocol. Blood samples will be collected and stored every 4 months and will form the basis of separately funded studies to identify new biomarkers associated with the outcomes. DISCUSSION: We have evidence that the biomarker-led care regime will be effective at preventing graft dysfunction and expect this to feed through to graft survival. This trial will confirm the benefit of routine screening and lead to a greater understanding of how to keep kidney transplants working longer. TRIAL REGISTRATION: Current Controlled TrialsISRCTN46157828.

Type: Article
Title: Can a combined screening/treatment programme prevent premature failure of renal transplants due to chronic rejection in patients with HLA antibodies: study protocol for the multicentre randomised controlled OuTSMART trial
Open access status: An open access version is available from UCL Discovery
DOI: 10.1186/1745-6215-15-30
Publisher version: http://dx.doi.org/10.1186/1745-6215-15-30
Language: English
Additional information: © 2014 Dorling et al.; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Keywords: Human leukocyte antigen antibodies, renal transplantation, premature allograft failure, chronic rejection, screening, tacrolimus, mycophenolate mofetil, clinical trial, randomised controlled trial, randomized controlled trial, KCTU, CTU, trials unit, diabetes, kidney, graft failure, biomarker, biomarker-led care, DSA, non-DSA, multicentre, immunosuppression, usual care, treatment as usual, standard care, blinded, unblinded, EME funded, NIHR, optimised, optimized, intention-to-treat, per protocol, HUMAN-LEUKOCYTE ANTIGEN, MYCOPHENOLATE-MOFETIL, FOLLOW-UP, KIDNEY-TRANSPLANTATION, ALLOGRAFT DYSFUNCTION, GRAFT FAILURE, RECIPIENTS, CYCLOSPORINE, TACROLIMUS, RITUXIMAB
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy > Practice and Policy
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Infection, Immunity and Inflammation Dept
URI: https://discovery.ucl.ac.uk/id/eprint/1433576
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