Heart TransplantationPhase 3PROTECTNCT00966836
Prevention of Transplant Atherosclerosis With Everolimus and Anti-cytomegalovirus Therapy
A Phase 3 study testing Pre-emptive strategy with valganciclovir plus everolimus, Prophylaxis with valganciclovir plus mycophenolate and Prophylaxis with valganciclovir plus everolimus in people with Heart Transplantation and Cardiac Allograft Vasculopathy, run by University of Bologna at 1 site in Italy.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Heart Transplantation, Cardiac Allograft Vasculopathy, Cytomegalovirus Infection
- What is being tested?
- Pre-emptive strategy with valganciclovir plus everolimus, Prophylaxis with valganciclovir plus mycophenolate and Prophylaxis with valganciclovir plus everolimus
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 1 siteItaly
- Study dates
- Apr 2009to Apr 2012
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 13Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
Italy1 site, 1 recruiting
- Recruiting
Azienda Ospedaliero-Universitaria S Orsola Malpighi
Bologna
Luciano Potena, MD PhD
About this study
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
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.
- Being tested
- Pre-emptive strategy with valganciclovir plus everolimus, Prophylaxis with valganciclovir plus mycophenolate, Prophylaxis with valganciclovir plus everolimus, Pre-emptive mycophenolate
- Keywords
- Heart Transplantation, Cardiac Allograft Vasculopathy, Cytomegalovirus Infection, Everolimus, Valganciclovir, Mycophenolate
- Medical subject headings
- Cytomegalovirus Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Pre-emptive strategy with valganciclovir plus everolimusDrug
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 with valganciclovir plus mycophenolateDrug
Patients will receive 3 months of oral valganciclovir with mycophenolate and standard cyclosporine and prednisone for maintenance immunosuppression
Prophylaxis with valganciclovir plus everolimusDrug
Patients will receive valganciclovir for 3 months after transplant. Everolimus plus reduced cyclosporine and prednisone will be used for maintenance immunosuppression
Pre-emptive mycophenolateDrug
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
| Study group | Role | What they receive |
|---|---|---|
| Pre-emptive everolimus | Experimental | Not described Receives: Drug: Pre-emptive strategy with valganciclovir plus everolimus |
| Prophylaxis mycophenolate | Experimental | Not described Receives: Drug: Prophylaxis with valganciclovir plus mycophenolate |
| Prophylaxis Everolimus | Experimental | Not described Receives: Drug: Prophylaxis with valganciclovir plus everolimus |
| Pre-emptive mycophenolate | Active comparator | Not described Receives: Drug: Pre-emptive mycophenolate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in maximal intimal thickness
Measured: one year
Secondary outcomes (1)
CMV infection
Measured: one year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Aug 2009 (estimated)
- Study startApr 2009
- Primary completionApr 2012 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Heart TransplantationStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Bologna
- Sponsor type
- University, hospital or other
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00966836
- Sponsor's protocol ID
- PROTECT 2008-006980-35
- Acronym
- PROTECT
- Status last verified
- Aug 2009
- First submitted
- 26 Aug 2009
- Last updated
- 27 Aug 2009
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 19416774Potena 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.
PubMed 17609604Hill 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.
PubMed 18091519Vernooij 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.
PubMed 39807668Vernooij 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.
PubMed 38700045
Study at a glance
From the registry record, last updated by the sponsor on 27 Aug 2009. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00966836
- Acronym / sponsor ID
- PROTECT / PROTECT 2008-006980-35
- Keywords
- Heart Transplantation, Cardiac Allograft Vasculopathy, Cytomegalovirus Infection, Everolimus, Valganciclovir, Mycophenolate
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- University of BolognaUniversity, hospital or other
- Study start
- Apr 2009
- Primary completion
- Apr 2012 (estimated)
- First posted
- 27 Aug 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Pre-emptive everolimus | Experimental | Drug: Pre-emptive strategy with valganciclovir plus everolimus |
| Prophylaxis mycophenolate | Experimental | Drug: Prophylaxis with valganciclovir plus mycophenolate |
| Prophylaxis Everolimus | Experimental | Drug: Prophylaxis with valganciclovir plus everolimus |
| Pre-emptive mycophenolate | Active comparator | Drug: Pre-emptive mycophenolate |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (13 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Pre-emptive strategy with valganciclovir plus everolimusPatients 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 | Drug | Pre-emptive everolimus |
| Prophylaxis with valganciclovir plus mycophenolatePatients will receive 3 months of oral valganciclovir with mycophenolate and standard cyclosporine and prednisone for maintenance immunosuppression | Drug | Prophylaxis mycophenolate |
| Prophylaxis with valganciclovir plus everolimusPatients will receive valganciclovir for 3 months after transplant. Everolimus plus reduced cyclosporine and prednisone will be used for maintenance immunosuppression | Drug | Prophylaxis Everolimus |
| Pre-emptive mycophenolatePatients 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 | Drug | Pre-emptive mycophenolate |
Primary outcome
Change in maximal intimal thickness
Time frame: one year
1 secondary outcome
CMV infection
Time frame: one year
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Aug 2009.
- Background: PubMed 19416774Potena 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.
- Background: PubMed 17609604Potena 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.
- Background: PubMed 18091519Hill 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.
- Derived from this study: PubMed 39807668Vernooij 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.
- Derived from this study: PubMed 38700045Vernooij 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Pre-emptive strategy with valganciclovir plus everolimus, Prophylaxis with valganciclovir plus mycophenolate and Prophylaxis with valganciclovir plus everolimus in people with Heart Transplantation and Cardiac Allograft Vasculopathy, run by University of Bologna at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 27 Aug 2009. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Luciano Potena, MD PhD (+390516364526, luciano.potena2@unibo.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in maximal intimal thickness (time frame: one year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00966836, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Aug 2009.