Condition category
Injury, Occupational Diseases, Poisoning
Date applied
16/07/2007
Date assigned
22/08/2007
Last edited
10/05/2016
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Dr Richard Borrows

ORCID ID

Contact details

Department of Nephrology and Renal Transplantation
Queen Elizabeth Hospital
Edgbaston
Birmingham
B15 2TH
United Kingdom
+44 (0)121 627 5715
richard.borrows@uhb.nhs.uk

Additional identifiers

EudraCT number

ClinicalTrials.gov number

NCT00541814

Protocol/serial number

RRK3367

Study information

Scientific title

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

Acronym

CNIM-SRT

Study hypothesis

Calcineurin Inhibitor minimisation is effective in protecting renal transplants from chronic allograft nephropathy.

Ethics approval

North Staffordshire Local research Ethics Committee gave approval on the 20th September 2007 (ref: 07/H1204/103)

Study design

Prospective randomised controlled open-label parallel-group trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Not specified

Trial type

Prevention

Patient information sheet

Condition

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during which the calcineurin inhibitor will be either targeted to a specified low blood level of 50-100 ng/ml, or withdrawn completely (depending on randomisation).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

Phase

Not Specified

Drug names

Cicolsporin

Primary outcome measures

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 trial start date

01/08/2007

Overall trial end date

01/12/2009

Reason abandoned

Eligibility

Participant 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

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

90

Participant 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

Recruitment start date

01/08/2007

Recruitment end date

01/12/2009

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Department of Nephrology and Renal Transplantation
Birmingham
B15 2TH
United Kingdom

Sponsor information

Organisation

University Hospital Birmingham NHS Foundation Trust (UK)

Sponsor details

Research and Developement Department
4th Floor
Nuffield House
Queen Elizabeth Hospital
Birmingham
B15 2TH
United Kingdom
+44 (0)121 472 1311
chris.counsell@uhb.nhs.uk

Sponsor type

Hospital/treatment centre

Website

http://www.uhb.nhs.uk

Funders

Funder type

Industry

Funder name

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

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes

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