The Efficacy of Everolimus in Reducing Total Native Kidney Volume in Polycystic Kidney Disease Transplanted Recipients

Study Overview
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Brief Summary
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The investigators multicenter randomized open-labelled study will investigate the efficacy of an everolimus based immunosuppression in reducing total native kidney volume in kidney recipients with autosomal dominant polycystic kidney disease compared to a calcineurin inhibitor-based immunosuppression.

Detailed Description
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Kidney graft recipients receiving a firs kidney graft (between 6 months and 5 years post-transplantation) will be randomized 1:1 to receive an everolimus based immunosuppression (in association with steroids and mycophenolate mofetil) or to continue their calcineurin inhibitor-based immunosuppression regimen. The primary objective will be the reduction of total native kidney volume after a 2-years treatment period.

Official Title
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An Open-labelled Multicenter Randomized Study on the Efficacy of Everolimus in Reducing Total Native Kidney Volume in Kidney Transplanted Patients With Autosomal Dominant Polycystic Kidney Disease

Conditions
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Autosomal Dominant Polycystic Kidney Disease

Intervention / Treatment
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* Drug: Everolimus
* Drug: Calcineurin inhibitors maintenance


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age between 18 and 75 years-old recipients of a first kidney graft between 6 month and 5 years ago with a stable eGFR above 30 ml/min/1,73m2 contraception for female recipients to avoid pregnancy valid health Insurance during the study period Exclusion Criteria: signed informed consent not obtained

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Everolimus<br>everolimus based immunosuppression | Drug: Everolimus<br>* Change from a calcineurin inhibitors-based immunosuppression to an everolimus-based immunosuppression<br>* Other names: everolimus conversion;|
| Active Comparator: Calcineurin<br>Calcineurin inhibitors maintenance | Drug: Calcineurin inhibitors maintenance<br>* Usual treatment<br>* Other names: calcineurin-inhibitors based immunosuppression;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total native kidney volume variation | measurements of total native kidney volume with a MRI | 24 months after randomization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Volume variation of the biggest liver cyst | Measurements of the biggest liver cyst volume with a MRI | 24 months after randomization | 
| Interstitial Fibrosis/Tubular Atrophy variation | IF/TA quantification using Banff criteria during a kidney biopsy | 24 months after randomization | 
| % interstitial fibrosis using Red Sirius staining | % fibrosis quantified using a morphometry software | 24 months after randomization | 
| Calculated Estimated Glomerular Filtration rate | calculated estimated GFR | At baseline, 1 month, 6 months, 12 months, 18 and 24 months | 
| Measured Glomerular Filtration rate | measured GFR | At baseline and 24 months | 
| Proteinuria | Measurement | At baseline, 1 month, 6 months, 12 months, 18 and 24 months | 
| systolic and diastolic blood pressure | Clinic measurement | At baseline, 1 month, 6 months, 12 months, 18 and 24 months | 
| Occurrence of diabetes or hyperlipidemia | Measurements | up to 24 months | 
| Occurrence of neoplasia | Medical chart reporting | up to 24 months | 
| Development of HLA Donor Specific Antibody (DSA) | V0, 1 year and 2 years after randomization | At baseline, 1 month, 6 months, 12 months, 18 and 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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DSA, liver, kidney transplantation, IF/TA, fibrosis, mTOR inhibitors, calcineurin inhibitors, Autosomal dominant polycystic kidney disease, cyst, kidney