Clinical trial NCT01927588: Evaluation of Early Use of Everolimus (EVE) on Cytomegalovirus (CMV) Infection in Renal Transplant Recipients
Official title: An Exploratory Evaluation of Early Use of Everolimus (EVE) on Tacrolimus (TAC)-Based Immunosuppressive Regiment vs. Mycophenolate Sodium (MPS) on Cytomegalovirus (CMV) Infection in Renal Transplant Recipients.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Cytomegalovirus Infections
Keywords: Certican
Renal Transplant
Cytomegalovirus Infection
Lead sponsor: Fundação Pró Rim
Sponsor class: OTHER
First posted: 2013-08-22
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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;

Primary outcomes:
measure: Cytomegalovirus (CMV) infection investigation
timeFrame: one year
Secondary outcomes:
measure: Transplant biopsies
timeFrame: One year
measure: C4d method
timeFrame: one year
measure: Polyoma identification
timeFrame: One year
Other outcomes:
Locations:
Study officials:
affiliation: Fundação Pró Rim
name: Luciane M. Deboni, Msc
role: PRINCIPAL_INVESTIGATOR
References: