Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT00401856 |
| Other study ID # |
2004CD006B |
| Secondary ID |
Eudract 2004-002 |
| Status |
Completed |
| Phase |
Phase 4
|
| First received |
|
| Last updated |
|
| Start date |
December 2007 |
| Est. completion date |
April 2, 2013 |
Study information
| Verified date |
September 2021 |
| Source |
Royal Brompton & Harefield NHS Foundation Trust |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
The aim of this study is to determine if therapy with the aldosterone antagonist, Eplerenone,
is associated with improved remodeling of the left ventricle in patients with cardiomyopathy.
We will determine if any benefit to cardiac remodeling is associated with improved clinical
outcomes, including improved exercise capacity and reduced incidence of major adverse cardiac
events such as death, hospitalization for heart-failure, serious heart rhythm disturbances
and transplantation.
The null hypothesis is that therapy with Eplerenone over 12 months is associated with an
improvement in cardiopulmonary exercise capacity and furthermore that treatment is associated
with improved clinical outcomes.
In order to test this hypothesis we will study stable patients on optimal drug therapy with
documented cardiomyopathy using a trial design where therapy will be randomized,
double-blinded and placebo-controlled. This will reduce the likelihood of any 'researcher
bias'. Patients will be recruited from the Heart-failure Service at the Royal Brompton
Hospital.
Description:
Our aim is to recruit 140 patients (based on statistical power calculation in). These
patients will be recruited from the cardiology clinics at The Royal Brompton Hospital as well
as from a database of patients who have previously undergone imaging.
The study will be a double-blinded, placebo-controlled randomized study. The recruited
patients would have had an established diagnosis of cardiomyopathy as documented by the
history, examination and characteristic echocardiographic + ECG findings. The patients would
also have had a CMR scan demonstrating late gadolinium hyperenhancement previously. These
patients will have been established on maximally tolerated doses of standard drugs used in
the treatment of cardiomyopathy (including ACE inhibitors and beta blockers as appropriate)
and the doses of these drugs would have remained unchanged in the 2 months preceding
enrollment to the trial. Patients would be randomized to receive a maximal dose of 50mg
eplerenone or placebo. The study dose of Eplerenone to be used will be initially 25mg once
daily (one tablet). After 4 weeks, provided it has been well tolerated with no problems the
dose will be increased to the usual maintenance dose of 50mg once daily (two tablets). For
patients receiving placebo, the number of tablets received will match the Eplerenone group at
the same time points.
Baseline tests will include CMR evaluation of ventricular function using a magnetic field
strength of 1.5 Tesla (T). The initial scan will assess ventricular size and function and LV
mass. Blood tests will be taken prior to the scan (at the time of intravenous cannulation)
for urea and electrolytes, liver function, cytokines, and collagen markers. In addition,
echocardiograms, 24 hour Holter monitors will be fitted and metabolic exercise tests (MVO2)
will be performed as part of the cardiac assessment at baseline, 6 and 12 months.
The findings of the initial scans and tests will be correlated with base line parameters and
also prospectively compared with the occurrence of events over 6 and 12 month time periods.
During the follow up period all events including death, cardiac arrest, cardiac
transplantation, arrhythmic events, implantation of implantable cardiac
defibrillators/biventricular pacemakers, NYHA classification, escalation of treatment and
hospitalization will be recorded. There will be regular clinical reviews at 1 week, 2 weeks,
4 weeks and then at 3, 6, 9 and 12 months during the study period at which point blood tests
will be taken including a check of renal function to look for evidence of hyperkalaemia and
renal failure which may be a result of treatment with eplerenone. Other reported adverse
effects and any withdrawals from the trial as a direct result of these effects will also be
recorded. After the treatment/placebo has been stopped we will contact all patients within
one week by telephone to ensure that there has been no deterioration in symptoms and will
review all patients within four weeks for a post-treatment follow up visit to monitor their
blood-pressure, kidney function and ensure that there has been no evidence of problems.
Patients will also be asked to complete a Minnesota Living with Heart Failure (MLWHF)
Questionnaire at baseline visit and again during the 6 and 12 month visits.
It is hoped that the study will reveal that patients with cardiomyopathy who are treated with
eplerenone will have evidence of regression of fibrosis with a concomitant improvement in
diastolic function as demonstrated by CMR scanning, as well as in clinical outcomes by Holter
and metabolic exercise testing and markers of collagen turnover.
