- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01046045
Everolimus Rescue Immunosuppression in the Treatment of Chronic Allograft Dysfunction in Renal Transplant Recipients
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.
Study Overview
Status
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 4
Contacts and Locations
Study Locations
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Hong Kong, Hong Kong
- Prince of Wales Hospital
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Active Comparator: Everolimus
before and after everolimus; in other words, comparison of specified outcome before and after treatment with everolimus
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everolimus at an initial daily loading dose between 1 and 4 mg dose of everolimus will be adjusted to maintain a trough everolimus level between 5 and 12 ng/mL
Other Names:
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Active Comparator: Calcineurin-inhibitor immunosuppression
Cyclosporin-based immunosuppression without everolimus
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everolimus at an initial daily loading dose between 1 and 4 mg dose of everolimus will be adjusted to maintain a trough everolimus level between 5 and 12 ng/mL
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
change in glomerular filtration rate decline rate and histological degree of fibrosis before and after treatment with everolimus
Time Frame: 12 months
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12 months
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Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
estimated glomerular filtration rate at 12 months
Time Frame: 12 months
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12 months
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morphometric studies
Time Frame: 12 months
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12 months
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cytokines before and after everolimus conversion
Time Frame: 12 months
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12 months
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Kai Ming Chow, MBChB, Chinese University of Hong Kong, Prince of Wales Hospital
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- CRE-2008.004-T
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Chronic Allograft Dysfunction in Renal Transplantation
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University Hospital, BordeauxRecruitingLung Transplantation | Antibody Mediated Rejection | Chronic Lung Allograft DysfunctionFrance
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University of ZurichWithdrawnLung Transplantation | Chronic Lung Allograft Dysfunction | Rejection Lung Transplant
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Astellas Pharma IncAstellas Pharma Canada, Inc.CompletedRenal Transplantation | Chronic Renal Allograft FailureCanada
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University of MichiganGenentech, Inc.TerminatedChronic Lung Allograft Dysfunction | Disorder Related to Lung TransplantationUnited States
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National Institute of Allergy and Infectious Diseases...Clinical Trials in Organ TransplantationTerminatedKidney Transplantation | Primary Renal Allograft CandidateUnited States
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Technical University of MunichUniversity Hospital, Essen; University of Erlangen-Nürnberg; Heinrich-Heine University... and other collaboratorsTerminatedRenal Transplantation | Transplantation, Kidney | Chronic Allograft Nephropathy | GraftingGermany
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Shanghai Zhongshan HospitalUnknownChronic Allograft DysfunctionChina
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The University of QueenslandIsopogen; Cell and Tissue TherapiesCompletedChronic Lung Allograft Dysfunction (CLAD)Australia
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Prof. Dr. Jens HohlfeldHannover Medical SchoolCompletedChronic Lung Allograft Dysfunction (CLAD)Germany
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AmgenCompletedHyperparathyroidism | End Stage Renal Disease | Chronic Kidney Disease | Kidney Transplantation | Chronic Renal Failure | Hypophosphatemia | Kidney Disease | Chronic Allograft Nephropathy | Disordered Mineral Metabolism | Post Renal TransplantationUnited States, Canada, France, Italy, Belgium, Switzerland, Spain, Australia, Germany, Austria, Poland
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