Study to Evaluate the Safety and Efficacy of Switching Calcineurin Inhibitor to Everolimus After Kidney Transplantation in Adults

A Prospective, Open-label, Controlled, Randomized Study to Evaluate the Safety and Efficacy of Switching Calcineurin Inhibitor to Everolimus After 90 to 150 Days After Kidney Transplantation in Adults, Maintaining Corticosteroid and Mycophenolate Sodium Compared to Patients Who Will Maintain the Use of Calcineurin Inhibitor

The purpose of this study is to demonstrate the efficacy and safety in the use of everolimus, with its onset after 3 months of treatment with calcineurin inhibitor.

Study Overview

• Status: Unknown
• Conditions: Immunosuppression; Kidney Transplant
• Intervention / Treatment: Drug: Everolimus; Drug: calcineurin inhibitor

Detailed Description

The patient who met the inclusion and exclusion criteria will be included in the study and randomized into two groups in the third month post transplant, they will be in use of tacrolimus, corticosteroids and Mycophenolate sodium. The group 1 will undergo a conversion from calcineurin inhibitor to Everolimus within 1 day (overnight), group 2 will be maintained with the initial immunosuppression. We will start Everolimus at 1 mg 2x/day and three days after the beginning we will adjust the dose by the serum levels, which will be kept in 6 to 10ng/dL. The doses of corticosteroids and Mycophenolate sodium will be retained. There will be performed renal biopsies at randomization and after 12 months. The glomerular filtration rate will be calculated monthly using the MDRD.

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 4

Contacts and Locations

Study Locations

• Brazil
  • Rio de Janeiro, Brazil, 21041-030
    • Hospital Federal de Bonsucesso

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients aged from 18 to 65 years old
• First transplantation recipients
• PRA < 30%
• Living or cadaveric donor
• Stable renal function
• Patients not pregnant or breastfeeding , where pregnancy is defined as the woman status from conception to gestation conclusion, through a positive beta hCG test (>5mUI/mL)
• Provided written informed consent form

Exclusion Criteria:

• Cadaveric donor with expanded criterion
• Multiple organs transplantation
• Kidney cold ischemia time > 24 hours
• Severe rejection episode - Banf >IIA
• Glomerular filtration rate < 35mL/min
• Presence of hard to treat dyslipidemia - severe hypercholesterolemia (>350mg/dL) or hypertriglyceridemia (>500mg/dL)
• Proteinuria > 800mg/24h
• Patients with history of malignancy of any organic system, treated or not, within 5 years, with or without evidence of local recurrence or metastases, other than localized basal cell carcinoma
• Female with childbearing potential without using a reliable contraceptive method.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Everolimus	Drug: Everolimus; Group will switch calcineurin inhibitor to everolimus within 1 day (overnight).; Other Names: Certican
Active Comparator: calcineurin inhibitor	Drug: calcineurin inhibitor; Group will maintain their initial immunosuppression therapy with calcineurin inhibitor; Other Names: Tacrolimus, Cyclosporin, NeoOral, Prograf

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from Baseline in Creatinine Clearance at 24 months	The primary objective is to demonstrate the effectiveness and non-inferiority of treatment with everolimus, by assessing renal function, in comparison with the use of calcineurin inhibitor.	baseline and two years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with Adverse Events	The secondary objective is to demonstrate the safety by comparing rejection episodes, graft loss, infection, cancer and death in the control group	baseline and two years

Collaborators and Investigators

• Sponsor: Deise de Boni Monteiro de Carvalho
• Investigators: Study Chair: Francisco G Miloski, MD, Physician; Study Chair: Tereza Matuck, MD, Chief of the Nephrology Department; Study Chair: Regina Sousa, Head Nurse of The Nephrology Department

Study record dates

Study Major Dates

• Study Start: November 1, 2011
• Primary Completion (Anticipated): November 1, 2013
• Study Completion (Anticipated): November 1, 2013

Study Registration Dates

• First Submitted: October 11, 2011
• First Submitted That Met QC Criteria: October 19, 2011
• First Posted (Estimate): October 20, 2011

Study Record Updates

• Last Update Posted (Estimate): October 20, 2011
• Last Update Submitted That Met QC Criteria: October 19, 2011
• Last Verified: October 1, 2011

More Information

Terms related to this study

• Keywords: Immunosuppression; Everolimus; Transplant; Kidney; Graft function
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Dermatologic Agents; Antifungal Agents; Tacrolimus; Everolimus; Cyclosporine; Cyclosporins; Calcineurin Inhibitors
• Other Study ID Numbers: CRAD001ABR17T