A Clinical Trial to Assess the Efficacy and Safety of the Conversion to Everolimus

An Open-label Randomized Controlled Clinical Trial to Assess the Efficacy and Safety of the Conversion to Everolimus 3 Months After Kidney Transplantation.

The study hypotheses to be tested in this study are:

• Conversion to everolimus at 3 months post-transplantation is safe and effective;
• Accurate noninvasive molecular diagnostic tests can replace biopsy at 3 months pre-conversion (for the diagnosis of subclinical cellular and/or humoral rejection, tissue fibrosis and calcineurin inhibitor-induced nephrotoxicity) in kidney transplant recipients;
• Follow-up biopsy at 12 months post-conversion (for the diagnosis of tissue fibrosis) can be replaced with accurate noninvasive molecular diagnostic tests in kidney transplant recipients.

Study Overview

• Status: Unknown
• Conditions: Kidney Transplant Recipients
• Intervention / Treatment: Drug: Tacrolimus; Drug: Everolimus

• Study Type: Interventional
• Enrollment (Anticipated): 120
• Phase: Phase 4

Contacts and Locations

Study Locations

• Brazil
  • RS
    • Porto Alegre, RS, Brazil, 90035-903
      • Recruiting
      • Hospital De Clinicas De Porto Alegre

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Patients undergoing their first living- or deceased-donor kidney transplant who maintain a functioning graft 3 months post-transplant;
• Older than 18 years;
• Panel-reactive antibodies lower than 20%;
• Baseline immunosuppression with tacrolimus, mycophenolate sodium (MPS) and prednisone at randomization at 3 months.

Exclusion Criteria:

• eGFR < 35 mL/min at randomization;
• Urine protein-to-creatinine ratio > 0.8 at randomization;
• Episode of acute rejection with Banff histological classification > 1A in the first 3 months post-transplant;
• Cholesterol > 350 mg/dL or triglycerides > 400 mg/dL with therapy at randomization;
• Active infection at randomization;
• Chronic liver disease;
• Refusal to participate in the study;
• Contraindications to kidney biopsy;
• Biopsy findings at 3 months post-transplant including borderline rejection, cellular rejection or antibody-mediated rejection.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Tacrolimus; The subjects included in the study will be clinically followed up for at least 12 months. The patients will be selected at 3 months post-transplant according to inclusion and exclusion criteria and randomized in a 1:1 ratio for conversion to everolimus or maintenance of tacrolimus therapy. Intervention arm: Tacrolimus	Drug: Tacrolimus; TACROLIMUS (C0 = 5-10 ng/mL) + MPS 1440 mg + Pred
ACTIVE_COMPARATOR: Everolimus; The subjects included in the study will be clinically followed up for at least 12 months. The patients will be selected at 3 months post-transplant according to inclusion and exclusion criteria and randomized in a 1:1 ratio for conversion to everolimus or maintenance of tacrolimus therapy. Intervention arm: Everolimus	Drug: Everolimus; Everolimus (C0 = 6-10 ng/mL) + MPS 1440 mg + Pred

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate cumulative patient and graft survival at 12 months post conversion	Patient and graft survival will be evaluated one year after randomization by Kaplan-Meier analysis	one year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of estimated glomerular filtration rate 12 months post-conversion	- To assess the efficacy of conversion from tacrolimus to everolimus 12 months post-conversion by measuring the estimated glomerular filtration rate using the Modification of Diet in Renal Disease (MDRD) equation	one year

Collaborators and Investigators

• Sponsor: Hospital de Clinicas de Porto Alegre
• Investigators: Principal Investigator: Luiz Felipe S. Gonçalves, MD, HCPA

Study record dates

Study Major Dates

• Study Start: February 1, 2012
• Primary Completion (ANTICIPATED): July 1, 2014
• Study Completion (ANTICIPATED): July 1, 2014

Study Registration Dates

• First Submitted: May 8, 2012
• First Submitted That Met QC Criteria: May 30, 2012
• First Posted (ESTIMATE): May 31, 2012

Study Record Updates

• Last Update Posted (ESTIMATE): May 31, 2012
• Last Update Submitted That Met QC Criteria: May 30, 2012
• Last Verified: August 1, 2011

More Information

Terms related to this study

• Keywords: everolimus; tacrolimus; renal transplantation; molecular evaluation
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Calcineurin Inhibitors; Tacrolimus; Everolimus
• Other Study ID Numbers: CRAD001ABR19T