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

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

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.

Study Overview

• Status: Completed
• Conditions: Autosomal Dominant Polycystic Kidney Disease
• Intervention / Treatment: Drug: Everolimus; Drug: Calcineurin inhibitors maintenance

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 3
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Le Kremlin-Bicêtre, France, 94275
    • Bicetre Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Everolimus; everolimus based immunosuppression	Drug: Everolimus; Change from a calcineurin inhibitors-based immunosuppression to an everolimus-based immunosuppression; Other Names: everolimus conversion
ACTIVE_COMPARATOR: Calcineurin; Calcineurin inhibitors maintenance	Drug: Calcineurin inhibitors maintenance; Usual treatment; Other Names: calcineurin-inhibitors based immunosuppression

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Collaborators: Novartis
• Investigators: Principal Investigator: Hélène François, MD, PhD, Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 14, 2014
• Primary Completion (ACTUAL): November 11, 2017
• Study Completion (ACTUAL): November 11, 2017

Study Registration Dates

• First Submitted: April 28, 2014
• First Submitted That Met QC Criteria: May 8, 2014
• First Posted (ESTIMATE): May 9, 2014

Study Record Updates

• Last Update Posted (ACTUAL): December 10, 2018
• Last Update Submitted That Met QC Criteria: December 7, 2018
• Last Verified: December 1, 2018

More Information

Terms related to this study

• Keywords: kidney transplantation; kidney; liver; fibrosis; Autosomal dominant polycystic kidney disease; mTOR inhibitors; cyst; DSA; calcineurin inhibitors; IF/TA
• Additional Relevant MeSH Terms: Urologic Diseases; Congenital Abnormalities; Genetic Diseases, Inborn; Joint Diseases; Musculoskeletal Diseases; Muscular Diseases; Musculoskeletal Abnormalities; Abnormalities, Multiple; Kidney Diseases, Cystic; Ciliopathies; Kidney Diseases; Polycystic Kidney Diseases; Polycystic Kidney, Autosomal Dominant; Arthrogryposis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Everolimus; Calcineurin Inhibitors
• Other Study ID Numbers: P 090804; 2012-004265-41 (EUDRACT_NUMBER)