Sirolimus Associated With Tacrolimus at Low Doses in Elderly Kidney Transplant Patients

Sirolimus Associated With Tacrolimus at Low Doses in Elderly Kidney Transplant Patients: A Prospective Randomized Controlled Trial

There is no consensus on the best immunosuppressive regimen in elderly people. The aim of this study will be to evaluate the efficacy of sirolimus associated with tacrolimus in elderly kidney transplant recipients. The investigators will conduct a single-center prospective randomized study comparing the combination of tacrolimus with sirolimus at reduced dose rate (tacrolimus + sirolimus group) against tacrolimus with mycophenolate (tacrolimus + mycophenolate group). The investigators will include all kidney transplant patients over 60 years of age. The investigators will evaluate estimated glomerular filtration rate and incidence of cytomegalovirus in 12 month follow-up.

Study Overview

• Status: Completed
• Conditions: Cytomegalovirus Infections; Disorder Related to Renal Transplantation
• Intervention / Treatment: Drug: tacrolimus; Drug: mycophenolate; Drug: Prednisone; Drug: Basiliximab; Drug: Thymoglobulin; Drug: sirolimus

Detailed Description

Study Design

This will be a single-center, prospective, 12-month randomized controlled trial aiming to compare sirolimus associated with tacrolimus in elderly renal transplant patients as to safety and incidence of cytomegalovirus (CMV) infection.

Treatments

In the control group (Tacrolimus + Mycophenolate) the investigators will use tacrolimus (starting with 0.1 mg/kg twice daily adjusted to target serum levels by 4-8ng/ml at the third month and then 3-7ng/ml from the third month to the 12th month) and mycophenolate sodium 720 mg twice daily. A dose reduction of mycophenolate sodium to 720 mg/day will be accepted due to possible side effects of the drug.

In the treatment group (Tacrolimus + sirolimus) the investigators will use tacrolimus (starting with 0.1 mg/kg twice daily adjusted to target serum levels by 4-8 ng/ml at the third month and then 3-7 ng/ml from the third month to the 12th month) and sirolimus 2 mg/day (adjusted serum levels at 4-8 ng/ml throughout the study period).

In all groups, patients will receive prednisone 30 mg/day (in the first month with weekly reductions up to 5 mg/day at the end of the second month). Induction therapy consisted of basiliximab or antithymocyte globulin (Thymoglobulin, Genzyme®). Thymoglobulin will be used in patients with panel reactivity class I greater than 50 % (at a dose of 1mg/kg for 5 days).

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients aged more than 60 years and recipients of compatible renal transplant

Exclusion Criteria:

1. Receptors of multiple organs;
2. non-heart beating donors;
3. donors aged under 5 or over 65 years;
4. Patients with body mass index greater than 35

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Tacrolimus + Mycophenolate; The investigators wil be used tacrolimus (starting with 0.1 mg/kg twice daily adjusted to target serum levels by 4-8ng/ml at the third month and then 3-7ng/ml from the third month to the 12th month) and mycophenolate sodium 720 mg twice daily. A dose reduction of mycophenolate sodium to 720 mg/day will be accepted due to possible side effects of the drug. Prednisone 30 mg/day in the first month. Induction therapy consisted of basiliximab or thymoglobulin if panel reactivity class I greater than 50 %	Drug: tacrolimus; Other Names: Prograf; FK506; Drug: mycophenolate; Other Names: Myfortic; Mycophenolate Sodium; Drug: Prednisone; Prednisone 30mg/day; Other Names: Meticorten; Drug: Basiliximab; Basiliximab 20mg (first and fourth day) if panel reactivity class I less than 50 %; Other Names: Simulect; Drug: Thymoglobulin; Thymoglobulin at a dose of 1mg/kg for 5 days if panel reactivity class I greater than 50 %; Other Names: antithymocyte globulin
Experimental: Tacrolimus + Sirolimus; The investigators will be used tacrolimus (starting with 0.1 mg/kg twice daily adjusted to target serum levels by 4-8 ng/ml at the third month and then 3-7 ng/ml from the third month to the 12th month) and sirolimus 2 mg/day (adjusted serum levels at 4-8 ng/ml throughout the study period). Prednisone 30 mg/day in the first month. Induction therapy consisted of basiliximab or thymoglobulin if panel reactivity class I greater than 50 %	Drug: tacrolimus; Other Names: Prograf; FK506; Drug: Prednisone; Prednisone 30mg/day; Other Names: Meticorten; Drug: Basiliximab; Basiliximab 20mg (first and fourth day) if panel reactivity class I less than 50 %; Other Names: Simulect; Drug: Thymoglobulin; Thymoglobulin at a dose of 1mg/kg for 5 days if panel reactivity class I greater than 50 %; Other Names: antithymocyte globulin; Drug: sirolimus; Other Names: Rapamycin; Rapamune

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in estimated glomerular filtration rate from baseline	The primary end-point will be evaluated the estimated glomerular filtration rate (eGFR) over 12 months of renal transplantation. The investigators will be measure the change in eGFR during 12 month follow-up. Glomerular filtration rate will be estimated by the MDRD equation (Modification of Diet in Renal Disease).	Baseline, 1 month, 3 months, 6 months and 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of cytomegalovirus Infection (CMV)	The secondary end-point will be evaluated the incidence of cytomegalovirus (CMV) infection. CMV infection will be defined based on detection of CMV viral replication (CMV pp65 antigenemia more than zero) in asymptomatic patients. CMV disease will be defined based on the evidence of CMV infection with related symptoms. For the positive cases treatment will be carried out with ganciclovir 5 mg/kg/day twice daily adjusted for renal function for a minimum of 14 days.	Weekly from baseline until the third month. After in 4, 5, 6, 8, 10 and 12 months.

Collaborators and Investigators

• Sponsor: Associação Médico Espírita de Botucatu

Study record dates

Study Major Dates

• Study Start: January 1, 2014
• Primary Completion (Actual): January 1, 2015
• Study Completion (Actual): January 1, 2016

Study Registration Dates

• First Submitted: February 5, 2016
• First Submitted That Met QC Criteria: February 11, 2016
• First Posted (Estimate): February 17, 2016

Study Record Updates

• Last Update Posted (Estimate): February 17, 2016
• Last Update Submitted That Met QC Criteria: February 11, 2016
• Last Verified: February 1, 2016

More Information

Terms related to this study

• Keywords: cytomegalovirus; Kidney transplantation; aged; sirolimus
• Additional Relevant MeSH Terms: Virus Diseases; Infections; DNA Virus Infections; Herpesviridae Infections; Cytomegalovirus Infections; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Anti-Inflammatory Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Antifungal Agents; Antitubercular Agents; Antibiotics, Antitubercular; Calcineurin Inhibitors; Prednisone; Tacrolimus; Mycophenolic Acid; Sirolimus; Basiliximab; Thymoglobulin; Antilymphocyte Serum
• Other Study ID Numbers: 16966913.6.0000.5411

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No