Calcineurin Inhibitor Minimisation in Renal Transplant recipients with Stable allograft function: A prospective randomised controlled trial

ISRCTN	ISRCTN60081949
DOI	https://doi.org/10.1186/ISRCTN60081949
ClinicalTrials.gov number	NCT00541814
Secondary identifying numbers	RRK3367

Submission date: 16/07/2007
Registration date: 22/08/2007
Last edited: 26/02/2019

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Injury, Occupational Diseases, Poisoning

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

Not provided at time of registration

Contact information

Dr Richard Borrows
Scientific

Department of Nephrology and Renal Transplantation
Queen Elizabeth Hospital
Edgbaston
Birmingham
B15 2TH
United Kingdom

Phone	+44 (0)121 627 5715
Email	richard.borrows@uhb.nhs.uk

Study information

Study design	Prospective randomised controlled open-label parallel-group trial
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	Not specified
Study type	Prevention
Scientific title	Calcineurin Inhibitor Minimisation in Renal Transplant recipients with Stable allograft function: A prospective randomised controlled trial
Study acronym	CNIM-SRT
Study objectives	Calcineurin Inhibitor minimisation is effective in protecting renal transplants from chronic allograft nephropathy.
Ethics approval(s)	North Staffordshire Local research Ethics Committee gave approval on the 20th September 2007 (ref: 07/H1204/103)
Health condition(s) or problem(s) studied	Renal transplantation; chronic allograft nephropathy
Intervention	Patients who fullfill 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: Cyclosporin minimisation Group 2: Cyclosporin withdrawal At this point paticipants will undergo assessment of the primary and secondary outcome measures. The treatment period comprises three stages: Stage 1: A 2 week period during which the patient will be stabilised on mycophenolate sodium 720 mg twice daily (in place of azathioprine). Stage 2: A 3 month period during which the calcineurin inhibitor will be either targeted to a specified low blood level of 50-100 ng/ml, or withdrawn completely (depending on randomisation). Stage 3: 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.
Intervention type	Drug
Pharmaceutical study type(s)
Phase	Not Specified
Drug / device / biological / vaccine name(s)	Cicolsporin
Primary outcome measure	To compare renal allograft markers of damage and evolving injury in biopsies immediately pre study and at the end of the study. The primary tissue assessments will comprise: 1. Index of chronic damage (an objective measure of the amount of chronic damage, shown to be a powerful indicator of prognosis in non-allograft renal biopsies) 2. Interstitial fibrosis quantification by Sirius Red staining 3. TGF-Beta expression 4. P-selectin expression and leukocyte infiltration (macrophage) 5. Fibroblast function 6. Epithelial mesenchymal transformation markers 7. Markers of apoptosis 8. Electron microscopy
Secondary outcome measures	The following will also be assessed immediately pre study and at the end of the study: 1. Renal: 1.1. Serum creatinine 1.2. Estimated Glomerular Filtration Rate (GFR) 1.3. Isotopic GFR 1.4. Urinary Albumin : Creatinine Ratio (ACR) 1.5. Graft loss 2. Immunological: 2.1. Acute clinical rejection episodes between both groups 2.2. Sub-clinical rejection on month exit biopsy 2.3. Donor specific and non-donor specific anti-HLA antibody formation 2.4. T cell responses 3. Infection: 3.1. Cytomegalovirus (CMV) PCR 3.2. BK polyoma virus PCR 3.3. Bacterial (fever, with identification of an organism by culture) 4. Cardiovascular: 4.1. Fasting lipid profile 4.2. Serum uric acid 4.3. Serum C-Reactive Protein (CRP) 4.4. Serum fibrinogen 4.5. Asymmetric Dimethylarginine (ADMA) levels 4.6. Ambulatory blood pressure 4.7. Arterial stiffness 4.8. Left ventricular mass on echocardiography 5. Malignancy 6. Patient Survival
Overall study start date	01/08/2007
Completion date	01/12/2009

Eligibility

Participant type(s)	Patient
Age group	Adult
Sex	Both
Target number of participants	90
Key inclusion criteria	1. Adult recipients of a first kidney transplant 2. A functioning kidney allograft (with estimated Glomerular Filtration Rate [eGFR] by Modification of Diet in Renal Disease [MDRD] >30 ml/min/1.73m^ 2) and be between 1 and 5 years post transplantation 3. Stable allograft function, as defined by no greater than 10% rise in serum creatinine in the preceding 6 months, on ciclosporin and azathioprine based immunosuppression 4. Minimal proteinuria, evidenced as urine albumin:creatinine ratio <50mg/mmol
Key exclusion criteria	1. <18 years of age 2. Pregnancy or suspicion of pregnancy confirmed by positive b-HCG pregnancy test 3. Female patients unwilling to take effective contraception for study duration 4. Untreated ureteric obstruction on ultrasound of allograft 5. Recurrent urosepsis 6. Severe systemic infection 7. Untreated significant (>50%) renal artery stenosis on magnetic resonance angiography performed prior to study 8. History of acute allograft rejection 9. History of myocardial infarction 10. History of malignancy in previous 5 years (excluding non-melanomatous tumours limited to skin) 11. Symptomatic ischaemic heart disease 12. Hepatitis B surface antigen positive, hepatitis C positive or HIV positive 13. Recipient of combined organ transplantation (e.g. pancreas / kidney; liver / kidney) 14. Recipient of ABO-incompatible kidney 15. Greater than 1 HLA mismatch at either the B or DR locus 16. Peak HLA antibody Panel Reactivity (PRA) greater than 10% 17. Recipient who underwent HLA desensitisation procedure prior to transplantation
Date of first enrolment	01/08/2007
Date of final enrolment	01/12/2009

Locations

Countries of recruitment

England
United Kingdom

Study participating centre

Department of Nephrology and Renal Transplantation

Birmingham
B15 2TH
United Kingdom

Sponsor information

University Hospital Birmingham NHS Foundation Trust (UK)
Hospital/treatment centre

Research and Developement Department
4th Floor
Nuffield House
Queen Elizabeth Hospital
Birmingham
B15 2TH
England
United Kingdom

Phone	+44 (0)121 472 1311
Email	chris.counsell@uhb.nhs.uk
Website	http://www.uhb.nhs.uk
"ROR"	https://ror.org/014ja3n03

Funders

Funder type

Industry

University Hospital Birmingham Renal Research Fund supported by an unrestricted grant form Novartis Pharmaceuticals (UK)

No information available

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
Publication and dissemination plan	Not provided at time of registration
IPD sharing plan

Editorial Notes

26/02/2019: No publications found, verifying study status with principal investigator
10/05/2016: No publications found, verifying study status with principal investigator.