Calcineurin Inhibitor Minimisation in Renal Transplant Recipients With Stable Allograft Function (CNIM-SRT)
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|ClinicalTrials.gov Identifier: NCT00541814|
Recruitment Status : Unknown
Verified September 2008 by University Hospital Birmingham.
Recruitment status was: Recruiting
First Posted : October 10, 2007
Last Update Posted : September 8, 2008
|First Submitted Date ICMJE||October 9, 2007|
|First Posted Date ICMJE||October 10, 2007|
|Last Update Posted Date||September 8, 2008|
|Study Start Date ICMJE||October 2007|
|Primary Completion Date||Not Provided|
|Current Primary Outcome Measures ICMJE
||To compare renal allograft markers of damage and evolving injury in biopsies immediately pre study and at the end of the study [ Time Frame: 16 months ]|
|Original Primary Outcome Measures ICMJE||Same as current|
|Current Secondary Outcome Measures ICMJE
|Original Secondary Outcome Measures ICMJE||Same as current|
|Current Other Pre-specified Outcome Measures||Not Provided|
|Original Other Pre-specified Outcome Measures||Not Provided|
|Brief Title ICMJE||Calcineurin Inhibitor Minimisation in Renal Transplant Recipients With Stable Allograft Function|
|Official Title ICMJE||Calcineurin Inhibitor Minimisation in Renal Transplant Recipients With Stable Allograft Function: A Prospective Randomised Controlled Trial|
|Brief Summary||The purpose of this trial is to ascertain whether the withdrawal of calcineurin inhibitors (CNI) will lead to less kidney transplant damage when compared with minimisation. The investigators will assess this by comparing the degree of damage on kidney biopsies taken before and after minimisation/withdrawal of CNI.|
Renal transplantation is the most effective form of treatment for end-stage renal failure. It doubles long-term survival and has major socioeconomic and health benefits compared to patients who remain on dialysis. Graft survival in the UK is 90% at one year and greater than 75% at 5 years [UKTransplant, 2004], with better survival of grafts from living donors compared with deceased. However, by 15 years post-transplantation, over 50% of recipients who are still alive have returned to dialysis. Indeed, premature allograft failure is now one of the leading causes of end stage renal disease. As short-term outcomes of renal transplantation continue to improve, increasing attention is being paid to this late attrition of renal allografts.
It is recognised that calcineurin inhibitor (CNI) nephrotoxicity is a major factor in late renal allograft failure and dysfunction. In fact, withdrawal of CNI from patients with deteriorating graft function may improve graft function. However, there is abundant evidence that histological renal allograft damage may progress even in the absence of changes in renal function - i.e. declining renal function is a late marker of renal damage, and therefore institution of therapies (including CNI minimisation) to slow this process may be "too little, too late".
CNI minimisation may be optimised by three major routes. Firstly, by minimising the CNI beyond 12 months post transplantation when the risk of acute rejection is at its greatest. Secondly, by performing a renal biopsy in patients prior to CNI minimisation and avoiding CNI minimisation in patients with inflammation on the biopsy. Finally, converting azathioprine to mycophenolate prior to CNI minimisation should have a renoprotective effect.
The type of CNI we will investigate is cyclosporine.
Patients who fulfill the study entry criteria will require a renal allograft biopsy prior to randomisation to exclude acute rejection, recurrent disease or de novo glomerulonephritis. Those patients with an acceptable biopsy will proceed to randomisation on a 1:1 basis into 2 groups:
Group 1: CNI [Cyclosporine] minimisation; Group 2: CNI [Cyclosporine] withdrawal.
At this point participants will undergo assessment of the primary and secondary outcome measures. The treatment period comprises three stages:
Firstly, a 2 week period during which the patient will be stabilised on mycophenolate sodium 720mg twice daily (in place of azathioprine);
Secondly, a 3 month period during which the CNI [Cyclosporine} will be either targeted to a specified low blood level of 50-100ng/ml, or withdrawn completely (depending on randomisation);
Thirdly, a 12 month maintenance period on the new immunosuppression regimen.
During the first two stages, patients will be reviewed every 2 weeks. This 2-weekly follow-up will continue for the first two months of the third stage of the study, and then visits will be reduced to monthly. At these visits routine blood and urine analysis will be performed as per routine clinical practice.
At the end of the third stage of the study (i.e. 16 months after randomisation) the participants will undergo the second assessment of the primary and secondary outcome measures. This will signify study end for the individual study participant.
|Study Type ICMJE||Interventional|
|Study Phase ICMJE||Phase 4|
|Study Design ICMJE||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
|Condition ICMJE||Chronic Allograft Nephropathy|
|Intervention ICMJE||Drug: Cyclosporine
Target drug level 50-100 ng/ml or cyclosporine withdrawal
Other Name: Neoral
|Study Arms ICMJE||
|Publications *||Not Provided|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Unknown status|
|Estimated Enrollment ICMJE
|Original Estimated Enrollment ICMJE||Same as current|
|Estimated Study Completion Date ICMJE||February 2010|
|Primary Completion Date||Not Provided|
|Eligibility Criteria ICMJE||
|Ages ICMJE||18 Years and older (Adult, Older Adult)|
|Accepts Healthy Volunteers ICMJE||No|
|Contacts ICMJE||Contact information is only displayed when the study is recruiting subjects|
|Listed Location Countries ICMJE||United Kingdom|
|Removed Location Countries|
|NCT Number ICMJE||NCT00541814|
|Other Study ID Numbers ICMJE||RRK3367
ISRCTN No. 60081949
|Has Data Monitoring Committee||Yes|
|U.S. FDA-regulated Product||Not Provided|
|IPD Sharing Statement ICMJE||Not Provided|
|Responsible Party||Not Provided|
|Study Sponsor ICMJE||University Hospital Birmingham|
|PRS Account||University Hospital Birmingham|
|Verification Date||September 2008|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP