Chronic Allograft Dysfunction in Renal Transplantation Clinical Trial
Official title:
Impact and Efficacy of Everolimus Rescue Immunosuppression in the Treatment of Chronic Allograft Dysfunction in Renal Transplant Recipients
Despite the remarkable improvement in short-term patient and graft survival among the
recipients of kidney transplants, the progressive renal dysfunction (chronic allograft
dysfunction) accompanied by chronic interstitial fibrosis, tubular atrophy, vascular
occlusive changes and glomerulosclerosis remains the chief cause of graft loss. As a result
of this damage from immunologic and non-immunologic injury, the long-term survival of kidney
transplants has changed little during the past decade. And, among the non-immunologic
factors, calcineurin inhibitor nephrotoxicity has been shown to be the most common factor
leading to long-term graft damage and progression to graft failure. This is further
supported by the previous finding that long-term use of calcineurin inhibitor-based therapy
leads to deterioration in kidney function, even in recipients of non-renal organ
transplants.
The growing interest in calcineurin inhibitor minimisation protocols to optimize renal
transplant outcome offers a new therapeutic options in the management of patients with
chronic allograft dysfunction. Recently, mammalian target-of-rapamycin inhibitors (mTOR
inhibitors) including everolimus has been shown to achieve an improvement of long-term
function through an early modulation of immunosuppressive regimen. In this aspect,
percutaneous renal graft biopsy represents an important diagnostic tool to allow
visualization of the lesions of chronic allograft dysfunction and therefore the ability to
delineate the potential improvement after introduction of everolimus. Histologic and
morphometric findings from a protocol-mandated biopsies obtained from renal transplant
recipients who are suffering from chronic allograft dysfunction and treated with everolimus
are needed to provide a clinical blueprint for the drug's efficacy, if confirmed.
| Status | Completed |
| Enrollment | 17 |
| Est. completion date | June 2013 |
| Est. primary completion date | November 2011 |
| Accepts healthy volunteers | No |
| Gender | Both |
| Age group | 18 Years to 65 Years |
| Eligibility |
Inclusion Criteria: - Aged 18-65 years - Biopsy-confirmed chronic allograft dysfunction or chronic allograft nephropathy, in the absence of acute rejection episode within the preceding 2 months - Proteinuria < 0.8 g/day (or spot urine protein < 0.8 g/g-Cr) in 2 consecutive samples within 8 weeks - Serum creatinine < 220 µmol/L or estimated glomerular filtration rate > 40 ml/min/1.73m2 by the Nankivell formula, which had been validated in kidney transplant recipients; this equation was expressed for use with a standard serum creatinine assay: glomerular filtration rate = 6.7/(standardized serum creatinine in µmol/L / 1000) + weight (kg)/4 - urea (mmol/L)/2 - 100 / height2 (m) + 35 if the subject is male (or 25 if the subject is female) - Willingness to give written consent and comply with the study protocol Exclusion Criteria: - Pregnancy, lactating or childbearing potential without effective method of birth control - Severe gastrointestinal disorders that interfere with their ability to receive or absorb oral medication - Serum cholesterol > 7.8 mmol/L and/or serum triglycerides > 4.5 mmol/L despite lipid-lowering agents before conversion - Systemic infection requiring therapy at study entry - Participation in any previous trial on everolimus or sirolimus - Patients receiving treatment of sirolimus or everolimus for other medical reasons within the past 12 months - On other investigational drugs within last 30 days - History of a psychological illness or condition such as to interfere with the patient's ability to understand the requirement of the study - History of non-compliance - Chronic lung disease - Known history of sensitivity or allergy to everolimus |
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
| Country | Name | City | State |
|---|---|---|---|
| Hong Kong | Prince of Wales Hospital | Hong Kong |
| Lead Sponsor | Collaborator |
|---|---|
| Chinese University of Hong Kong |
Hong Kong,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | change in glomerular filtration rate decline rate and histological degree of fibrosis before and after treatment with everolimus | 12 months | Yes | |
| Secondary | estimated glomerular filtration rate at 12 months | 12 months | Yes | |
| Secondary | morphometric studies | 12 months | No | |
| Secondary | cytokines before and after everolimus conversion | 12 months | No |