Evaluation of Early Use of Everolimus (EVE) on Cytomegalovirus (CMV) Infection in Renal Transplant Recipients
Status:
Unknown status
Trial end date:
2015-11-01
Target enrollment:
Participant gender:
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.