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

Primary Purpose

Heart Transplantation, Cardiac Allograft Vasculopathy, Cytomegalovirus Infection

Status
Unknown status
Phase
Phase 3
Locations
Italy
Study Type
Interventional
Intervention
Pre-emptive strategy with valganciclovir plus everolimus
Prophylaxis with valganciclovir plus mycophenolate
Prophylaxis with valganciclovir plus everolimus
Pre-emptive mycophenolate
Sponsored by
University of Bologna
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Heart Transplantation focused on measuring Heart Transplantation, Cardiac Allograft Vasculopathy, Cytomegalovirus Infection, Everolimus, Valganciclovir, Mycophenolate

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Azienda Ospedaliero-Universitaria S Orsola MalpighiRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Active Comparator

Arm Label

Pre-emptive everolimus

Prophylaxis mycophenolate

Prophylaxis Everolimus

Pre-emptive mycophenolate

Arm Description

Outcomes

Primary Outcome Measures

Change in maximal intimal thickness

Secondary Outcome Measures

CMV infection

Full Information

First Posted
August 26, 2009
Last Updated
August 26, 2009
Sponsor
University of Bologna
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1. Study Identification

Unique Protocol Identification Number
NCT00966836
Brief Title
Prevention of Transplant Atherosclerosis With Everolimus and Anti-cytomegalovirus Therapy
Acronym
PROTECT
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

2. Study Status

Record Verification Date
August 2009
Overall Recruitment Status
Unknown status
Study Start Date
April 2009 (undefined)
Primary Completion Date
April 2012 (Anticipated)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

Name of the Sponsor
University of Bologna

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Heart Transplantation, Cardiac Allograft Vasculopathy, Cytomegalovirus Infection
Keywords
Heart Transplantation, Cardiac Allograft Vasculopathy, Cytomegalovirus Infection, Everolimus, Valganciclovir, Mycophenolate

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
100 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Pre-emptive everolimus
Arm Type
Experimental
Arm Title
Prophylaxis mycophenolate
Arm Type
Experimental
Arm Title
Prophylaxis Everolimus
Arm Type
Experimental
Arm Title
Pre-emptive mycophenolate
Arm Type
Active Comparator
Intervention Type
Drug
Intervention Name(s)
Pre-emptive strategy with valganciclovir plus everolimus
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
Prophylaxis with valganciclovir plus mycophenolate
Intervention Description
Patients will receive 3 months of oral valganciclovir with mycophenolate and standard cyclosporine and prednisone for maintenance immunosuppression
Intervention Type
Drug
Intervention Name(s)
Prophylaxis with valganciclovir plus everolimus
Intervention Description
Patients will receive valganciclovir for 3 months after transplant. Everolimus plus reduced cyclosporine and prednisone will be used for maintenance immunosuppression
Intervention Type
Drug
Intervention Name(s)
Pre-emptive mycophenolate
Intervention Description
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
Primary Outcome Measure Information:
Title
Change in maximal intimal thickness
Time Frame
one year
Secondary Outcome Measure Information:
Title
CMV infection
Time Frame
one year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Luciano Potena, MD PhD
Phone
+390516364526
Email
luciano.potena2@unibo.it
First Name & Middle Initial & Last Name or Official Title & Degree
Francesco Grigioni, MD PhD
Phone
+390516364526
Email
francesco.grigioni@unibo.it
Facility Information:
Facility Name
Azienda Ospedaliero-Universitaria S Orsola Malpighi
City
Bologna
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Luciano Potena, MD PhD

12. IPD Sharing Statement

Citations:
PubMed Identifier
19416774
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.
Results Reference
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PubMed Identifier
17609604
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.
Results Reference
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PubMed Identifier
18091519
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.
Results Reference
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Prevention of Transplant Atherosclerosis With Everolimus and Anti-cytomegalovirus Therapy

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