Transplant Evidence Alert

The Transplant Evidence Alert provides a monthly overview of the 10 most important new clinical trials in organ transplantation, selected and reviewed by the Peter Morris Centre for Evidence in Transplantation (Oxford University).

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5-Year outcomes of the prospective and randomized CISTCERT study comparing steroid withdrawal to replacement of cyclosporine with everolimus in de novo kidney transplant patients

Transpl Int. 2021 Feb;34(2):313-326 doi: 10.1111/tri.13798.
Abstract

Withdrawal of either steroids or calcineurin inhibitors are two strategies to reduce treatment-related side effects and improve long-term outcomes of kidney transplantation. The CISTCERT study compared the efficacy and safety of these two strategies. In this multicenter, randomized controlled trial, 151 incident kidney transplant recipients received cyclosporine (CsA), mycophenolic acid (MPA), and steroids during three months, followed by either steroid withdrawal (CsA/MPA) or replacement of cyclosporine with everolimus (EVL) (EVL/MPA/steroids). 5-year patient survival (89% vs. 86%; P = NS) and death-censored graft survival (95% vs. 96%; P = NS) were comparable in the CsA/MPA and EVL/MPA/steroids arm, respectively. 51 CrEDTA clearance was comparable in the intention-to-treat analysis, but in the on-treatment population, the EVL/MPA/steroids arm exhibited a superior 51 CrEDTA clearance at 1 and 5 years after transplantation (61.6 vs. 52.4, P = 0.05 and 59.1 vs. 46.2ml/min/1.73 m2 , P = 0.042). Numerically more and more severe rejections were observed in the EVL/MPA/steroids arm, which also experienced a higher incidence of posttransplant diabetes (26% vs. 6%, P = 0.0016) and infections. No significant differences were observed in cardiovascular outcomes and malignancy. Both regimens provide an excellent long-term patient survival and graft survival. Regarding graft function, EVL/MPA/steroids is an attractive strategy for patients with good tolerability who remain free of rejection. (ClinicalTrials.gov number: NCT00903188; EudraCT Number 2007-005844-26).

CET Conclusion
Reviewer: Mr Simon Knight, Centre for Evidence in Transplantation, Nuffield Department of Surgical Sciences University of Oxford
Conclusion: This paper reports 5-year outcomes of the CISTERT study, which compared conversion from CNI to everolimus with steroid withdrawal strategies from 3-months post-transplant. The results are as one would expect from the two strategies – a slight improvement in GFR in patients who were able to tolerate everolimus, but with higher incidence of new-onset diabetes and rejection compared to the steroid withdrawal (and CNI continuation) arm. Graft and patient survival were excellent and similar in both arms. It is good to see investigators publishing long-term results from RCTs. As with many mTOR studies, treatment was poorly tolerated and the difference in GFR was absent in the modified intent-to-treat analysis. The study is likely underpowered as a number of patients originally randomised to everolimus failed to convert, and only 36-37% patients remained on the randomised treatment for the full 5 years of follow-up.
Methodological quality
Jadad score 3
Allocation concealment YES
Data analysis MODIFIED INTENT TO TREAT
Study Details
Aims: The aim of this study was to report the 5-year outcomes of the CISTERT study, a randomised controlled trial that compared the safety and efficacy of steroid withdrawal versus replacement of cyclosporine with everolimus at 3-months post-transplant, in de novo renal transplant recipients.
Interventions: Participants were randomised to switch to either steroid withdrawal or replace cyclosporine by everolimus at 3-months following transplantation.
Participants: 151 de novo kidney transplant patients.
Outcomes: The outcomes of interest included the assessment of glomerular filtration rate (GFR) at one year following transplantation, graft survival, patient survival, malignancies, infections, rejection episodes, diabetes, proteinuria and cardiovascular morbidity.
Follow Up: 5 years
Metadata
Funding: Industry funding
Publication type: Multicenter Study, Randomized Controlled Trial, Randomised Controlled Trial
Trial registration: ClinicalTrials.gov - NCT00903188
Organ: Kidney
Language: English
Author email: lissa.pipeleers@uzbrussel.be
MeSH terms: Cyclosporine; Everolimus; Graft Rejection; Graft Survival; Humans; Immunosuppressive Agents; Kidney Transplantation; Mycophenolic Acid; Prospective Studies; Steroids; 0 (Immunosuppressive Agents); 0 (Steroids); 83HN0GTJ6D (Cyclosporine); 9HW64Q8G6G (Everolimus); HU9DX48N0T (Mycophenolic Acid)