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| A randomised controlled trial comparing the use of sirolimus based biphasic immunosuppression with myfortic to allow early CalciNeurin Inhibitor (CNI) withdrawal in renal transplantation |
| Source of record | UK Trials |
| ISRCTN | ISRCTN76390219 |
| Date ISRCTN assigned | 16/10/2007 |
| Local reference number(s) | RMRCTV1 |
| Public title | A randomised controlled trial comparing the use of sirolimus based biphasic immunosuppression with myfortic to allow early CalciNeurin Inhibitor (CNI) withdrawal in renal transplantation |
| Scientific title | |
| Acronym | N/A |
| Disease/condition/study domain | Renal transplantation |
| Study hypothesis | 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. |
| Design/methodology | A single-centre open randomised controlled trial. |
| Research ethics review | 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. |
| Countries of trial | United Kingdom |
| Participants - 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 |
| Participants - 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 |
| Patient information material | |
| Anticipated start date | 01/10/2007 |
| Anticipated end date | 01/10/2009 |
| Status of trial | Ongoing |
| Target number of participants | 42 |
| Interventions | 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 |
| 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) |
| 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 |
| Sources of funding | 1. University Hospitals of Leicester NHS Trust (UK) 2. Funding is also being sought from Wyeth Pharma and Novartis |
| Sponsor name | University Hospitals of Leicester NHS Trust (UK) |
| Sponsor details | Leicester General Hospital Gwendolen Road Leicester United Kingdom LE5 4PW |
| Sponsor telephone | +44 (0)116 258 4604 |
| Sponsor email | yashajohari@doctors.net.uk |
| Contact name | Prof Michael Nicholson |
| Contact details | Department of Renal Transplantation Leicester General Hospital Gwendolen Road Leicester United Kingdom LE5 4PW |
| Contact telephone | +44 (0)116 258 4604 |
| Contact email | BB77@le.ac.uk |
| More information | For more up-to-date information please go to the ISRCTN link below. |
| Link to record in ISRCTN Register | ISRCTN76390219 |
| Date last extracted from ISRCTN register | 17/04/2008 |
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