Prevention of Transplant Atherosclerosis With Everolimus and Anti-cytomegalovirus Therapy

NCT ID: NCT00966836

Last Updated: 2009-08-27

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE3

Total Enrollment

100 participants

Study Classification

INTERVENTIONAL

Study Start Date

2009-04-30

Brief Summary

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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.

Detailed Description

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Conditions

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Heart Transplantation Cardiac Allograft Vasculopathy Cytomegalovirus Infection

Keywords

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Heart Transplantation Cardiac Allograft Vasculopathy Cytomegalovirus Infection Everolimus Valganciclovir Mycophenolate

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

NONE

Study Groups

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Pre-emptive everolimus

Group Type EXPERIMENTAL

Pre-emptive strategy with valganciclovir plus everolimus

Intervention Type DRUG

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

Prophylaxis mycophenolate

Group Type EXPERIMENTAL

Prophylaxis with valganciclovir plus mycophenolate

Intervention Type DRUG

Patients will receive 3 months of oral valganciclovir with mycophenolate and standard cyclosporine and prednisone for maintenance immunosuppression

Prophylaxis Everolimus

Group Type EXPERIMENTAL

Prophylaxis with valganciclovir plus everolimus

Intervention Type DRUG

Patients will receive valganciclovir for 3 months after transplant. Everolimus plus reduced cyclosporine and prednisone will be used for maintenance immunosuppression

Pre-emptive mycophenolate

Group Type ACTIVE_COMPARATOR

Pre-emptive mycophenolate

Intervention Type DRUG

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

Interventions

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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

Intervention Type DRUG

Prophylaxis with valganciclovir plus mycophenolate

Patients will receive 3 months of oral valganciclovir with mycophenolate and standard cyclosporine and prednisone for maintenance immunosuppression

Intervention Type 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

Intervention Type 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

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

70 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of Bologna

OTHER

Sponsor Role lead

Responsible Party

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University of Bologna

Locations

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Azienda Ospedaliero-Universitaria S Orsola Malpighi

Bologna, , Italy

Site Status RECRUITING

Countries

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Italy

Central Contacts

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Luciano Potena, MD PhD

Role: CONTACT

Phone: +390516364526

Email: [email protected]

Francesco Grigioni, MD PhD

Role: CONTACT

Phone: +390516364526

Email: [email protected]

References

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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.

Reference Type BACKGROUND
PMID: 19416774 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 17609604 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 18091519 (View on PubMed)

Vernooij RW, Michael M, Colombijn JM, Owers DS, Webster AC, Strippoli GF, Hodson EM. Pre-emptive treatment for cytomegalovirus viraemia to prevent cytomegalovirus disease in solid organ transplant recipients. Cochrane Database Syst Rev. 2025 Jan 14;1(1):CD005133. doi: 10.1002/14651858.CD005133.pub4.

Reference Type DERIVED
PMID: 39807668 (View on PubMed)

Vernooij RW, Michael M, Ladhani M, Webster AC, Strippoli GF, Craig JC, Hodson EM. Antiviral medications for preventing cytomegalovirus disease in solid organ transplant recipients. Cochrane Database Syst Rev. 2024 May 3;5(5):CD003774. doi: 10.1002/14651858.CD003774.pub5.

Reference Type DERIVED
PMID: 38700045 (View on PubMed)

Other Identifiers

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PROTECT 2008-006980-35

Identifier Type: -

Identifier Source: org_study_id