Prevention of Transplant Atherosclerosis With Everolimus and Anti-cytomegalovirus Therapy (PROTECT)

The recruitment status of this study is unknown because the information has not been verified recently.
Verified August 2009 by University of Bologna.
Recruitment status was  Recruiting
Sponsor:
Information provided by:
University of Bologna
ClinicalTrials.gov Identifier:
NCT00966836
First received: August 26, 2009
Last updated: NA
Last verified: August 2009
History: No changes posted
  Purpose

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.


Condition Intervention Phase
Heart Transplantation
Cardiac Allograft Vasculopathy
Cytomegalovirus Infection
Drug: Pre-emptive strategy with valganciclovir plus everolimus
Drug: Prophylaxis with valganciclovir plus mycophenolate
Drug: Prophylaxis with valganciclovir plus everolimus
Drug: Pre-emptive mycophenolate
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
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

Resource links provided by NLM:


Further study details as provided by University of Bologna:

Primary Outcome Measures:
  • Change in maximal intimal thickness [ Time Frame: one year ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • CMV infection [ Time Frame: one year ] [ Designated as safety issue: No ]

Estimated Enrollment: 100
Study Start Date: April 2009
Estimated Primary Completion Date: April 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Pre-emptive everolimus Drug: Pre-emptive strategy with valganciclovir plus everolimus
Patients will be monitored for CMV infection and receive valganciclovir only for positive PCR or antigenemia. Everolimus plus cyclosporine and prednisone will be used for maintenance immunosuppression
Experimental: Prophylaxis mycophenolate Drug: Prophylaxis with valganciclovir plus mycophenolate
Patients will receive 3 months of oral valganciclovir with mycophenolate and standard cyclosporine and prednisone for maintenance immunosuppression
Experimental: Prophylaxis Everolimus Drug: Prophylaxis with valganciclovir plus everolimus
Patients will receive valganciclovir for 3 months after transplant. Everolimus plus reduced cyclosporine and prednisone will be used for maintenance immunosuppression
Active Comparator: Pre-emptive mycophenolate Drug: Pre-emptive mycophenolate
Patients will be monitored for CMV infection and receive valganciclovir only for positive PCR or antigenemia. Mycophenolate plus standard cyclosporine and prednisone will be used for maintenance immunosuppression

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00966836

Contacts
Contact: Luciano Potena, MD PhD +390516364526 luciano.potena2@unibo.it
Contact: Francesco Grigioni, MD PhD +390516364526 francesco.grigioni@unibo.it

Locations
Italy
Azienda Ospedaliero-Universitaria S Orsola Malpighi Recruiting
Bologna, Italy
Sub-Investigator: Luciano Potena, MD PhD         
Sponsors and Collaborators
University of Bologna
  More Information

Publications:
Responsible Party: Angelo Branzi, University of Bologna
ClinicalTrials.gov Identifier: NCT00966836     History of Changes
Other Study ID Numbers: PROTECT 2008-006980-35
Study First Received: August 26, 2009
Last Updated: August 26, 2009
Health Authority: Italy: Agenzia Italiana del Farmaco (AIFA)

Keywords provided by University of Bologna:
Heart Transplantation
Cardiac Allograft Vasculopathy
Cytomegalovirus Infection
Everolimus
Valganciclovir
Mycophenolate

Additional relevant MeSH terms:
Cytomegalovirus Infections
Herpesviridae Infections
DNA Virus Infections
Virus Diseases
Mycophenolic Acid
Sirolimus
Mycophenolate mofetil
Everolimus
Valganciclovir
Ganciclovir
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antifungal Agents
Anti-Infective Agents
Anti-Bacterial Agents
Antiviral Agents

ClinicalTrials.gov processed this record on April 23, 2014