Evaluation of Early Use of Everolimus (EVE) on Cytomegalovirus (CMV) Infection in Renal Transplant Recipients

NCT ID: NCT01927588

Last Updated: 2013-08-22

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-08-31
• Study Completion Date: 2015-11-30

Brief Summary

CMV infection is common in transplant patients and can cause graft loss. CMV is a major factor in increasing morbidity, and post-transplant costs. The CMV infection is associated with many deleterious indirect effects including rejection, interstitial fibrosis and tubular atrophy, mortality. In addition to the potential for undesirable clinical outcomes associated with CMV, there is also a negative economic aspect. Patients who developed CMV events have been found to use significantly more inpatient and outpatient resources than patients without CMV disease. Universal prophylaxis is associated with high treatment cost and the potential for drug-related toxicity. It can be speculated that use of EVR may offer additional economic benefits in terms of decreased utilization associated with prevention of CMV disease, and reduce use of costly prophylaxis. Any efforts to reduce costs in renal transplants are very important and may have a great impact in total cost of a renal program. And the other hand, the clinical data suggest that EVR is associated with a decrease in CMV incidence compared to mycophenolic acid (MPA). CMV replication is dependent upon 1 ou 2 mTor pathways and in vitro studies support an association between mTor inhibitors and decreased CMV infection and disease. In cardiac transplantation, the use of EVR was associated with a lower incidence of CMV events. Some clinical trials data have also shown that use of EVR was associated with a lower incidence of CMV infection compared to MPA following renal transplantation. Brennan et al compared the incidence of CMV in three clinical trials using EVR versus MPA in De Novo renal transplants. They pooled for analysis the studies B201, B251 and A2309, all double-blind, randomized, parallel-groups that compared the incidence of freedom form and incidence of CMV between EVR groups and MPA groups. The results of this pooled analysis of over 2000 patients de novo renal transplant demonstrated that EVR was associated with a decrease in and delay in the time of onset of CMV events compared to MPA. Our hypothesis is that basiliximab in combination with low dose tacrolimus, everolimus and prednisone may result in comparable efficacy (BCAR) observed in patients receiving tacrolimus/mycophenolate/prednisone but with a better safety profile (CMV infection) and cost-effectiveness.

Detailed Description

Objectives:

Primary To investigate the effect of early use of EVL plus TAC dose reduced vs. MPS plus TAC full dose on CMV infection by antigenemia 12 month after transplantation in stable kidney transplant recipients.

Secondaries

To evaluate renal function by cGFR (MDRD) To evaluate the incidence of acute rejection and nephrotoxicity by protocol biopsies; To evaluate the incidence of poliomavirus, according to treatment group, by quantitative PCR the BKviremia in urine and biopsy sample.

Conditions

Cytomegalovirus Infections

Keywords

Certican; Renal Transplant; Cytomegalovirus Infection

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Everolimus+Tacrolimus+Prednisone

Certican 3mg/daily for 12 months TACreduced 0,15mg/Kg/daily for 12 months Steroids 1mg/Kg/daily for 12 months

Group Type: EXPERIMENTAL

Everolimus+Tacrolimus+Prednisone

Intervention Type: DRUG

Certican, introduced at Day7 post transplant + TACreduced + Steroids.

Mycophenolate+Tacrolimus+Prednisone

Myfortic 720mg twice daily for 12 months TACreduced full dose/Kg/daily for 12 months Steroids 1mg/Kg/daily for 12 months

Group Type: ACTIVE_COMPARATOR

Mycophenolate+Tacrolimus+Prednisone

Intervention Type: DRUG

Myfortic + Tacrolimus full + Steroids, as control arm.

Interventions

Everolimus+Tacrolimus+Prednisone

Certican, introduced at Day7 post transplant + TACreduced + Steroids.

Intervention Type: DRUG

Mycophenolate+Tacrolimus+Prednisone

Myfortic + Tacrolimus full + Steroids, as control arm.

Intervention Type: DRUG

Other Intervention Names

Certican; Tacrolimus; Prednisone; Myfortic; Tacrolimus; Prednisone

Eligibility Criteria

Inclusion Criteria

• Primary kidney transplants (living or deceased donors);

Exclusion Criteria

• Recipients of a second transplant;
• Recipients of multiple organs transplants;
• PRA > 50%;
• Chronic liver failure;
• Presence of uncontrolled hypercholesterolemia (≥ 250 mg/dL);
• Or hypertriglyceridemia (≥ 300 mg/dL).
• Leucocytes count < 1500 per microliter;
• Platelets count < 75000 per microliter;
• Proteinuria > 800mg/day;

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Fundação Pró Rim

OTHER

Sponsor Role: lead

Responsible Party

Luciane Mônica Deboni

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Luciane M. Deboni, Msc

Role: PRINCIPAL_INVESTIGATOR

Fundação Pró Rim

Central Contacts

Luciane M Deboni, Doctor, PI

Role: CONTACT

Phone: +55 47 96094320

Email: lmdeboni@terra.com.br

Karjan H Mazzoleni, Nurse, SC

Role: CONTACT

Phone: +55 47 99141713

Email: karjanhelena@gmail.com

Other Identifiers

CRAD001ABR29T

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

CRAD001ABR29T

Identifier Type: -

Identifier Source: org_study_id