Clinical trial NCT00966836: Prevention of Transplant Atherosclerosis With Everolimus and Anti-cytomegalovirus Therapy
Official title: Efficacy and Safety of Anti-cytomegalovirus Prophylaxis Versus Pre-emptive Approaches With Valganciclovir in Heart Transplant Recipients Treated With Everolimus or Mycophenolate. A Randomized Open-label Study for Prevention of Cardiaca Allograft Vasculopathy
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Heart Transplantation
Cardiac Allograft Vasculopathy
Cytomegalovirus Infection
Keywords: Heart Transplantation
Cardiac Allograft Vasculopathy
Cytomegalovirus Infection
Everolimus
Valganciclovir
Mycophenolate
Lead sponsor: University of Bologna
Sponsor class: OTHER
First posted: 2009-08-27
Enrollment: 100
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: PREVENTION

Brief summary: Cardiac allograft vasculopathy (CAV) is the major cause of long-term graft failure in heart transplant recipients. Although several immune-mediated and metabolic risk factors have been implicated in the pathogenesis of CAV, no effective therapy is currently available to treat established CAV and prevent its adverse outcomes. Therefore, the main clinical strategy is based on prevention and treatment of factors known to trigger its development. Although the mechanism is vague, cytomegalovirus (CMV) infection is believed to play a key role in CAV progression.

Two strategies involving administration of specific anti-CMV agents are recommended for prevention of CMV infection/disease: universal prophylaxis and preemptive therapy. The pros and cons of the two strategies are still debated, in the absence of randomized studies addressing graft-related outcomes and viral mechanisms of graft damage, and without any clear evidence of superiority of either approach.

The investigators conceived this randomized prospective project to compare the effect of preemptive anti-CMV strategy with universal anti-CMV prophylaxis on CMV infection and on one-year increase in coronary intimal thickening. Patients will be additionally randomized to receive either mycophenolate mofetil or everolimus, in light of the possible anti-CMV properties of everolimus.


Eligibility criteria: Inclusion Criteria:

* Age ≥ 18y
* Heart or heart-kidney combined transplant
* Positive CMV serology at the time of transplant
* Glomerular filtration rate ≥ 20 ml/min/1.73m2 with MDRD at randomization.
* Written informed consent

Exclusion Criteria:

* Panel Reactive Antibody ≥50%
* Less than 1000/mmc neutrophils at the time of randomization
* Less than 30,000/mmc platelets at the time of randomization
* Clinical significant infection in the 2 weeks prior to transplant
* Glomerular filtration rate \< 20 ml/min/1.73m2 estimated with MDRD formula at the time of randomization or hemodialysis treatment
* Intolerance towards valganciclovir, everolimus, mycophenolate or cyc-losporine
* Known contraindication to statin use
* Negative CMV serology at the time of transplant
* HIV positive testing
* Severe comorbidities that, based on investigator's judgment, contraindicate study drugs or procedures
* Potentially childbearing women who refuse to use contraceptives
* Participation to an interventional study in the 2 preceding weeks
* Unwillingness or inability to follow study procedure and to sign written in-formed consent

Primary outcomes:
measure: Change in maximal intimal thickness
timeFrame: one year
Secondary outcomes:
measure: CMV infection
timeFrame: one year
Other outcomes:
Locations:
city: Bologna
country: Italy
facility: Azienda Ospedaliero-Universitaria S Orsola Malpighi
Study officials:
References:
citation: Potena L, Grigioni F, Magnani G, Lazzarotto T, Musuraca AC, Ortolani P, Coccolo F, Fallani F, Russo A, Branzi A. Prophylaxis versus preemptive anti-cytomegalovirus approach for prevention of allograft vasculopathy in heart transplant recipients. J Heart Lung Transplant. 2009 May;28(5):461-7. doi: 10.1016/j.healun.2009.02.009.
citation: Potena L, Valantine HA. Cytomegalovirus-associated allograft rejection in heart transplant patients. Curr Opin Infect Dis. 2007 Aug;20(4):425-31. doi: 10.1097/QCO.0b013e328259c33b.
citation: Hill JA, Hummel M, Starling RC, Kobashigawa JA, Perrone SV, Arizon JM, Simonsen S, Abeywickrama KH, Bara C. A lower incidence of cytomegalovirus infection in de novo heart transplant recipients randomized to everolimus. Transplantation. 2007 Dec 15;84(11):1436-42. doi: 10.1097/01.tp.0000290686.68910.bd.