Cardiac TransplantationPhase 4EVERHEARTNCT01017029
Everolimus in de Novo Heart Transplant Recipients
A Phase 4 study testing Everolimus and Mycophenolate mofetil + Everolimus in people with Cardiac Transplantation, run by Novartis Pharmaceuticals at 12 sites in Italy.
Trial summary
The purpose of this study, in de novo heart transplant patients, is to evaluate whether delayed introduction of everolimus reduces the occurrence of wound healing problems, pericardial and/or pleural effusion and early acute renal insufficiency, as compared with immediate introduction of everolimus, in the firs six… Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Cardiac Transplantation
- What is being tested?
- Everolimus and Mycophenolate mofetil + Everolimus
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 182 participants
- Where
- 12 sitesItaly
- Study dates
- Sep 2009to Dec 2013
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female cardiac transplant candidates 18-65 years of age undergoing primary heart transplantation.
- Glomerular filtration rate (GFR by MDRD) ≥ 40 mL/min/1.73 m2 at randomization
Who cannot join
- Patients who are recipients of multiple solid organ transplants
- Patients who are HIV-positive or Hepatitis C positive (PCR only) or B-surface antigen positive;
- Presence of Donor/Recipients serological mismatch for Hepatitis B or C;
- Recipients of organ from donors positive for Hepatitis B-surface antigen;
- Panel Reactive Antibodies (cytotoxicity method) > 30%.
- Other protocol-defined inclusion/exclusion criteria may apply
Trial locations and contacts
12 sites in 1 country.
12 sites in 1 country
Italy12 sites
Novartis Investigative Site
Bari, BA, 70124
Novartis Investigative Site
Bologna, BO, 40138
Novartis Investigative Site
Cagliari, CA, 09134
Novartis Investigative Site
Milan, MI, 20162
Novartis Investigative Site
Naples, 80131
Novartis Investigative Site
Padova, PD, 35128
Novartis Investigative Site
Pavia, PV, 27100
Novartis Investigative Site
Roma, RM, 00152
Novartis Investigative Site
Siena, SI, 53100
Novartis Investigative Site
Torino, TO, 10126
Novartis Investigative Site
Udine, UD, 33100
Novartis Investigative Site
Verona, VR, 37126
About this study
Official title: Early vs. Delayed EVERolimus in de Novo HEART Transplant Recipients: Optimization of the Safety/Efficacy Profile (EVERHEART Study)
The purpose of this study, in de novo heart transplant patients, is to evaluate whether delayed introduction of everolimus reduces the occurrence of wound healing problems, pericardial and/or pleural effusion and early acute renal insufficiency, as compared with immediate introduction of everolimus, in the firs six months after heart transplantation.
- Conditions
- Cardiac Transplantation
- Being tested
- Everolimus, Mycophenolate mofetil + Everolimus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EverolimusDrug
Mycophenolate mofetil + EverolimusDrug
| Study group | Role | What they receive |
|---|---|---|
| Immediate introduction of everolimus | Active comparator | Not described Receives: Drug: Everolimus |
| Delayed introduction of everolimus | Experimental | delayed introduction) + Cyclosporin + steroids Receives: Drug: Mycophenolate mofetil + Everolimus |
What is being measured
The primary outcome is the main question the study is designed to answer.
Participants With at Least One Occurrence of Safety Composite Endpoint After 6 Months by Treatment Group
Comparison of 6-month cumulative incidence of safety composite endpoint (wound healing delay) related to initial transplant surgery, pleural/pericardial effusions and occurrence of acute renal insufficiency, defined as estimated glomerular filtration rate (eGFR) ≤ 30 mL/min/1.73 m2, between delayed everolimus arm and immediate everolimus arm
Measured: 6 months
Secondary outcomes (5)
Partcipants With at Least One Occurrence of Each Safety Composite Endpoint Event After 6 Months by Treatment Group
Measured: 6 months
Hazard Cox's Model Analysis of Pericardial/Pleural Effusions
Pericardial effusions: any pericardial effusion defined as at least moderate (i.e. measuring at least 2.0 cm in diastole, in the point of largest distance between the pericardial leaflets), with or without signs of hemodynamic compromise, or leading to drainage or to prolonged hospitalization. Pleural effusions: need for surgical drainage tubes for longer than 7 days after surgery and subsequent pleural effusions leading to drainage. CI = confidence interval, HR = hazard ratio, MDRD = Modification of Diet in Renal Disease
Measured: 6 months
Absolute and Percent Frequencies of Patients With LDL ≥ 100 mg/mL at 1, 3 and 6 Months, by Treatment Group
LDL = low density lipoprotein
Measured: 6 months
Participants With CMV Infection and CMV Syndrome/Disease After 6 Months by Treatment Group
CMV infection is defined as pp65 antigenemia or DNAemia
Measured: 6 months
Participants With at Least One Occurrence of Composite Treatment Failure Events
Comparison of 6-months cumulative incidence of composite treatment failure events (BPAR ≥ 2R, rejection with hemodynamic compromise, graft loss, or death) between delayed everolimus arm and immediate everolimus arm
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Nov 2009 (estimated)
- Study startSep 2009
- Primary completionDec 2013
- Study completionDec 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Cardiac TransplantationStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- 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 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 182 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01017029
- Sponsor's protocol ID
- CRAD001AIT16
- Other IDs
- 2009-011008-43, 2009
- Acronym
- EVERHEART
- Status last verified
- Dec 2014
- First submitted
- 19 Nov 2009
- Last updated
- 12 Jan 2015
- Results posted
- Yes, on ClinicalTrials.gov
Publications
Potena L, Pellegrini C, Grigioni F, Amarelli C, Livi U, Maccherini M, Masciocco G, Faggian G, Lilla Della Monica P, Gerosa G, Marraudino N, Corda M, Boffini M; EVERHEART Investigators. Optimizing the Safety Profile of Everolimus by Delayed Initiation in De Novo Heart Transplant Recipients: Results of the Prospective Randomized Study EVERHEART. Transplantation. 2018 Mar;102(3):493-501. doi: 10.1097/TP.0000000000001945.
PubMed 28930797
Study at a glance
From the registry record, last updated by the sponsor on 12 Jan 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Early vs. Delayed EVERolimus in de Novo HEART Transplant Recipients: Optimization of the Safety/Efficacy Profile (EVERHEART Study)
- ClinicalTrials.gov ID
- NCT01017029
- Acronym / sponsor ID
- EVERHEART / CRAD001AIT16
- Conditions
- Cardiac Transplantation
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 182 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- Sep 2009
- Primary completion
- Dec 2013 (actual)
- Study completion
- Dec 2013 (actual)
- First posted
- 20 Nov 2009 (estimated)
- Results
- Posted 18 Dec 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study, in de novo heart transplant patients, is to evaluate whether delayed introduction of everolimus reduces the occurrence of wound healing problems, pericardial and/or pleural effusion and early acute renal insufficiency, as compared with immediate introduction of everolimus, in the firs six months after heart transplantation.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Immediate introduction of everolimus | Active comparator | Drug: Everolimus |
| Delayed introduction of everolimus | Experimental | Drug: Mycophenolate mofetil + Everolimusdelayed introduction) + Cyclosporin + steroids |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Male or female cardiac transplant candidates 18-65 years of age undergoing primary heart transplantation.
- Glomerular filtration rate (GFR by MDRD) ≥ 40 mL/min/1.73 m2 at randomization
Key exclusion criteria (6 listed)
- Patients who are recipients of multiple solid organ transplants
- Patients who are HIV-positive or Hepatitis C positive (PCR only) or B-surface antigen positive;
- Presence of Donor/Recipients serological mismatch for Hepatitis B or C;
- Recipients of organ from donors positive for Hepatitis B-surface antigen;
- Panel Reactive Antibodies (cytotoxicity method) > 30%.
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 |
|---|---|---|
| Everolimus | Drug | Immediate introduction of everolimus |
| Mycophenolate mofetil + Everolimus | Drug | Delayed introduction of everolimus |
Primary outcome
Participants With at Least One Occurrence of Safety Composite Endpoint After 6 Months by Treatment Group
Time frame: 6 months
Comparison of 6-month cumulative incidence of safety composite endpoint (wound healing delay) related to initial transplant surgery, pleural/pericardial effusions and occurrence of acute renal insufficiency, defined as estimated glomerular filtration rate (eGFR) ≤ 30 mL/min/1.73 m2, between delayed everolimus arm and immediate everolimus arm
5 secondary outcomes
Partcipants With at Least One Occurrence of Each Safety Composite Endpoint Event After 6 Months by Treatment Group
Time frame: 6 months
Hazard Cox's Model Analysis of Pericardial/Pleural Effusions
Time frame: 6 months
Absolute and Percent Frequencies of Patients With LDL ≥ 100 mg/mL at 1, 3 and 6 Months, by Treatment Group
Time frame: 6 months
Participants With CMV Infection and CMV Syndrome/Disease After 6 Months by Treatment Group
Time frame: 6 months
Participants With at Least One Occurrence of Composite Treatment Failure Events
Time frame: 6 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jan 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 28930797Potena L, Pellegrini C, Grigioni F, Amarelli C, Livi U, Maccherini M, Masciocco G, Faggian G, Lilla Della Monica P, Gerosa G, Marraudino N, Corda M, Boffini M; EVERHEART Investigators. Optimizing the Safety Profile of Everolimus by Delayed Initiation in De Novo Heart Transplant Recipients: Results of the Prospective Randomized Study EVERHEART. Transplantation. 2018 Mar;102(3):493-501. doi: 10.1097/TP.0000000000001945.
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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.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
12 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Everolimus and Mycophenolate mofetil + Everolimus in people with Cardiac Transplantation, run by Novartis Pharmaceuticals at 12 sites 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 2 inclusion and 6 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: finished, as of the sponsor's last update on 12 Jan 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 18 Dec 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Participants With at Least One Occurrence of Safety Composite Endpoint After 6 Months by Treatment Group (time frame: 6 months). 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 NCT01017029, which also lists 1 linked publication.
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 12 Jan 2015.