A randomised controlled trial comparing the use of sirolimus based biphasic immunosuppression with myfortic to allow early CalciNeurin Inhibitor (CNI) withdrawal in renal transplantation

ISRCTN	ISRCTN76390219
DOI	https://doi.org/10.1186/ISRCTN76390219
Protocol serial number	RMRCTV1
Sponsor	University Hospitals of Leicester NHS Trust (UK)
Funders	University Hospitals of Leicester NHS Trust (UK), Funding is also being sought from Wyeth Pharma and Novartis

Submission date: 29/08/2007
Registration date: 16/10/2007
Last edited: 24/08/2012

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

Prof Michael Nicholson
Scientific

Department of Renal Transplantation
Leicester General Hospital
Gwendolen Road
Leicester
LE5 4PW
United Kingdom

Phone	+44 (0)116 258 4604

Study information

Primary study design	Interventional
Study design	A single-centre open randomised controlled trial.
Secondary study design	Randomised controlled trial
Scientific title
Study objectives	Most renal transplants last between 8-10 years. The commonest cause of their failure is chronic allograft nephropathy - a pathological process where the kidney becomes fibrotic. This fibrosis is partly due to calcineurin inhibitors- the immunosupressants which protect the transplant. The hypothesis to be tested in this study is that a combination of Myfortic and Sirolimus can be used to eliminate the calcineurin inhibitor Tacrolimus at 3 months post renal transplantation, thereby avoiding the long term detrimental effects of Tacrolimus on the development of renal allograft fibrosis.
Ethics approval(s)	1. UK Medicines and Healthcare products Regulatory Agency (MHRA) approval obtained on 01/08/2007 2. The Central Office for Research Ethics Committees (COREC) approval pending minor changes to study literature as of 15/08/2007. (Nottingham Research Ethics Committee 2, 1 Standard Court, Park Row, Nottingham, NG1 6GN, UK). We will submit to local ethics review body (Leicester General Hospital) when central ethics approval has been gained.
Health condition(s) or problem(s) studied	Renal transplantation
Intervention	Patients will be randomised to one of two drug regimens at three months post transplantation: Regimen 1: Tacrolimus: Twice daily oral doses as specified by attending physician to obtain trough levels of 5-15 ng/ml Prednisolone: Once daily 20 mg oral dose. This will be reduced to 5 mg daily over two months. Myfortic: Twice daily 720 mg oral dose Regimen 2: Sirolimus: Once daily oral dose as specified by attending physician to obtain trough levels of 10-15 ng/ml Prednisolone: Once daily 20 mg oral dose. This will be reduced to 5 mg daily over two months. Myfortic: Thrice daily 360 mg oral dose Duration of interventions: 2 years
Intervention type	Other
Primary outcome measure(s)	1. Renal allograft fibrosis at 6 months post-trial entry 2. Renal function as measured by change in the slope of the eGFR over a period of at least 2 years (least squares method)
Key secondary outcome measure(s)	1. Change in cystatin C concentrations at 6 and 12 months compared to baseline 2. Incidence of biopsy proven acute rejection. The diagnosis and graded severity of acute renal allograft rejection will be made by employing the 1997 Banff criteria 3. Renal allograft profibrotic gene expression determined by Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR) 4. Patient and graft survival at 6, 12 and 24 months post-trial entry 5. Comparison of blood pressure and the requirements for anti hypertensive therapy 6. Comparison of hyperlipidaemia (to include cholesterol, triglycerides, Low Density Lipoprotein [LDL] and High Density Lipoproteins [HDL]) and the requirement for treatment of elevated lipids 7. Proteinuria assessed by 24 hour urinary protein at 3, 6 and 12 months 8. Quality of life differences on the 36-item Short Form health survey (SF-36) at 6 and 12 months compared to baseline
Completion date	01/10/2009

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	All
Target sample size at registration	42
Key inclusion criteria	Patients will be eligible for the trial if all of the following criteria are met: 1. Age greater than or equal to 18 years 2. Patients receiving a primary or secondary renal allograft from a living related, living unrelated or heart-beating cadaveric donor 3. Patients with second transplants must have maintained their primary graft for at least six months after transplantation (with the exception of graft failure due to technical reasons) 4. Stable renal allograft function over the first 3 months post transplant 5. An absence of subclinical rejection on the 3 month protocol biopsy 6. A negative pregnancy test pre-protocol biopsy 7. Signed written informed consent
Key exclusion criteria	Patients will not be eligible for the trial if any of the following criteria apply: 1. Kidney transplantation from a non heart-beating donor 2. Patients suffering an acute rejection episode in the first 3 months post transplant with a Banff classification of 1b or above 3. Sub-clinical rejection seen in the 3-month protocol biopsy 4. Proteinuria >500 mg/24 hours 5. Estimated Glomerular Filtration Rate (eGFR) <40 mls/min (Cockcroft-Gault formula) 6. Evidence of active systemic or localised major infection at study entry 7. Known hypersensitivity to Tacrolimus, macrolide antibiotics or Myfortic 8. Use of any investigational drug or treatments within 28 days before study entry 9. Known or suspected malignancy within five years before study entry 10. Any condition which in the opinion of the investigator makes the patient unsuitable for entry into the study
Date of first enrolment	01/10/2007
Date of final enrolment	01/10/2009

Locations

Countries of recruitment

United Kingdom
England

Study participating centre

Department of Renal Transplantation

Leicester
LE5 4PW
United Kingdom

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
IPD sharing plan