Diastolic Heart FailureNCT00505336
The Effect of Eplerenone and Atorvastatin on Markers of Collagen Turnover in Diastolic Heart Failure
A study testing Eplerenone, No additional treatment and Atorvastatin in people with Diastolic Heart Failure, run by St Vincent's University Hospital, Ireland at 1 site in Ireland.
Trial summary
To investigate whether the medicines eplerenone or atorvastatin have a favourable effect on diastolic heart failure. Eplerenone is a drug that has been shown to be beneficial in Chronic Heart Failure due to pump failure. It can increase life expectancy and improve symptoms in these patients. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Diastolic Heart Failure
- What is being tested?
- Eplerenone, No additional treatment and Atorvastatin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 43 participants
- Where
- 1 siteIreland
- Study dates
- Apr 2006to Dec 2008
- Phase
- Interventional
- 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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Patients with diastolic heart failure.
- Diastolic heart failure is defined as symptoms of heart failure with an ejection fraction >45%, BNP >100pg/ml and Doppler evidence of diastolic dysfunction.
Who cannot join
- Clinically unstable as defined by any change in diuretic dose in the month prior to enrolment.
- Evidence of significant inflammatory disease or hepatic disease or metabolic bone disease which may alter parameters of collagen metabolism.
- Patients already receiving statin, aldosterone or eplerenone therapy
- Pregnant women and women of child bearing age
Trial locations and contacts
1 site in 1 country.
About this study
To investigate whether the medicines eplerenone or atorvastatin have a favourable effect on diastolic heart failure.
Eplerenone is a drug that has been shown to be beneficial in Chronic Heart Failure due to pump failure. It can increase life expectancy and improve symptoms in these patients. It is not known whether or not eplerenone might be beneficial in heart failure with normal pump function (diastolic heart failure).
Read more
Atorvastatin is one of a group of cholesterol lowering medicines called statins, which have been shown to reduce cardiovascular disease in patients irrespective of whether cholesterol levels are high or normal. It is not known whether atorvastatin also reduces fibrosis of the heart which is one of the causes of diastolic heart failure.
Study hypothesis
- To investigate the impact of aldosterone antagonism or statin therapy on markers of collagen turnover in patients with diastolic heart failure.
- To assess the impact of aldosterone antagonism or statin therapy on markers of diastolic dysfunction and indices of clinical well being in patients with diastolic heart failure.
Read the detailed description
Diastolic heart failure is a significant contributor to the heart failure syndrome. However, little work has been done on the causes of diastolic heart failure, and in contradistinction to those with systolic heart failure, little is know about the aetiology and therefore, there are few effective therapies.
It is generally believed that diastolic heart failure represents a problem with compliance and relaxation of the ventricle. One possible explanation for this is thought to be an abnormality of collagen structure in the myocardium. There are data from hypertensive populations as well as from hypertensive experimental models indicating an abnormal fibrotic process in patients with hypertensive heart disease. However, there are a few data on this potential aetiological explanation for diastolic heart failure.
It is now possible to measure serum markers of fibrosis in circulating blood. Work in this area has established the reproducibility and reliability of measurements of pro-collagen I and pro-collagen III amino-terminal, secreted as the collagen molecules are released from the fibroblast. These markers have been analysed in several settings, including normal individuals, hypertensive populations and in those with established heart failure due to systolic dysfunction. Recently we have completed a study on analysis of these factors in patients with proven diastolic heart failure. These data have demonstrated an increased activity of the amino terminal pro-collagen III (PIIINP) with a trend towards an increase in the amino-terminal pro-collagen I (PINP). Other relevant markers of the fibrotic process were not altered, including metalloproteinase enzymes (MMP) and tissue inhibitors of metalloproteinase enzymes (TIMP)
These observational data support the hypothesis that diastolic heart failure may be the result of an aggressive uncontrolled myocardial fibrotic process. The purpose of this project is to assess whether aldosterone inhibition or statin therapy may have an impact on increased levels of collagen markers, and thereby have a positive influence on parameters of diastolic function. Aldosterone is known to be a potent stimulus of the fibrotic process and therefore is a likely contributor. Support for this hypothesis comes from the observation in the systolic heart failure population where the administration of an aldosterone antagonist was found to be of benefit especially in those individuals who had serum evidence of heightened fibrotic activity. Statin therapy has been shown to reduce myocardial fibrosis in a rat model. Furthermore, preliminary data presented from the EPHESUS study has shown that greater benefits of eplerenone in those receiving concomitant statin therapy. We therefore propose to analyse the impact of atorvastatin therapy or aldosterone inhibition on markers of collagen turnover and also indices of diastolic function and markers of clinical well being.
We therefore propose to analyse the impact of aldosterone inhibition or statin therapy on markers of collagen turnover and also indices of diastolic function and markers of clinical well being.
- Conditions
- Diastolic Heart Failure
- Being tested
- Eplerenone, No additional treatment, Atorvastatin
- Keywords
- Diastolic heart failure, Markers of collagen turnover, Statins, Aldosterone receptor blockers
- Medical subject headings
- Heart Failure, Diastolic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EplerenoneDrug
Also called Inspra
oral Eplerenone titrated to 50mg for duration of 12 months
No additional treatmentOther
normal disease modifying therapy for heart failure i.e. ACE-I, beta blockers
AtorvastatinDrug
Also called Lipitor
oral Atorvastatin 40mg
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Eplerenone Receives: Drug: Eplerenone |
| 3 | Active comparator | no additional treatment Receives: Other: No additional treatment |
| 2 | Experimental | Atorvastatin Receives: Drug: Atorvastatin |
What is being measured
The primary outcome is the main question the study is designed to answer.
To investigate the impact of aldosterone antagonism or statin therapy on markers of collagen turnover in patients with diastolic heart failure.
Measured: 12 months
Secondary outcomes (3)
To assess the impact of aldosterone antagonism or statin therapy on markers of diastolic dysfunction by echocardiography
Measured: 12 months
To assess the impact of aldosterone antagonism or statin therapy on indices of clinical well being
Measured: 12 months
The assess the impact of aldosterone antagonism or statin therapy on diastolic indices by cardiac MRI
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jul 2007 (estimated)
- Study startApr 2006
- Primary completionJul 2008
- Study completionDec 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Diastolic Heart FailureStudies 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 43 participants (actual)
Sponsor and investigators
- Lead sponsor
- St Vincent's University Hospital, Ireland
- Sponsor type
- University, hospital or other
- Investigators
- Ken McDonald, MD FRCP, Study director, Heart Failure Unit, St Vincent's University HospitalGeorge Mak, MB MRCPI, Principal investigator, St Vincent's University Hospital, IrelandNiamh Murphy, MD MRCPI, Principal investigator, St Vincent's University Hospital, Ireland
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00505336
- Sponsor's protocol ID
- SVUH 042
- Status last verified
- Feb 2009
- First submitted
- 19 Jul 2007
- Last updated
- 11 Feb 2009
- Results posted
- No
- Data monitoring committee
- No
Publications
Mak GJ, Ledwidge MT, Watson CJ, Phelan DM, Dawkins IR, Murphy NF, Patle AK, Baugh JA, McDonald KM. Natural history of markers of collagen turnover in patients with early diastolic dysfunction and impact of eplerenone. J Am Coll Cardiol. 2009 Oct 27;54(18):1674-82. doi: 10.1016/j.jacc.2009.08.021.
PubMed 19850207
Study at a glance
From the registry record, last updated by the sponsor on 11 Feb 2009. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Eplerenone and Atorvastatin on Markers of Collagen Turnover in Diastolic Heart Failure
- ClinicalTrials.gov ID
- NCT00505336
- Acronym / sponsor ID
- SVUH 042
- Conditions
- Diastolic Heart Failure
- Keywords
- Diastolic heart failure, Markers of collagen turnover, Statins, Aldosterone receptor blockers
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 43 participants (actual)
- Lead sponsor
- St Vincent's University Hospital, IrelandUniversity, hospital or other
- Study start
- Apr 2006
- Primary completion
- Jul 2008 (actual)
- Study completion
- Dec 2008 (actual)
- First posted
- 23 Jul 2007 (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.
To investigate whether the medicines eplerenone or atorvastatin have a favourable effect on diastolic heart failure.
Eplerenone is a drug that has been shown to be beneficial in Chronic Heart Failure due to pump failure. It can increase life expectancy and improve symptoms in these patients. It is not known whether or not eplerenone might be beneficial in heart failure with normal pump function (diastolic heart failure).
Atorvastatin is one of a group of cholesterol lowering medicines called statins, which have been shown to reduce cardiovascular disease in patients irrespective of whether cholesterol levels are high or normal. It is not known whether atorvastatin also reduces fibrosis of the heart which is one of the causes of diastolic heart failure.
Study hypothesis
- To investigate the impact of aldosterone antagonism or statin therapy on markers of collagen turnover in patients with diastolic heart failure.
- To assess the impact of aldosterone antagonism or statin therapy on markers of diastolic dysfunction and indices of clinical well being in patients with diastolic heart failure.
Detailed description
Diastolic heart failure is a significant contributor to the heart failure syndrome. However, little work has been done on the causes of diastolic heart failure, and in contradistinction to those with systolic heart failure, little is know about the aetiology and therefore, there are few effective therapies.
It is generally believed that diastolic heart failure represents a problem with compliance and relaxation of the ventricle. One possible explanation for this is thought to be an abnormality of collagen structure in the myocardium. There are data from hypertensive populations as well as from hypertensive experimental models indicating an abnormal fibrotic process in patients with hypertensive heart disease. However, there are a few data on this potential aetiological explanation for diastolic heart failure.
It is now possible to measure serum markers of fibrosis in circulating blood. Work in this area has established the reproducibility and reliability of measurements of pro-collagen I and pro-collagen III amino-terminal, secreted as the collagen molecules are released from the fibroblast. These markers have been analysed in several settings, including normal individuals, hypertensive populations and in those with established heart failure due to systolic dysfunction. Recently we have completed a study on analysis of these factors in patients with proven diastolic heart failure. These data have demonstrated an increased activity of the amino terminal pro-collagen III (PIIINP) with a trend towards an increase in the amino-terminal pro-collagen I (PINP). Other relevant markers of the fibrotic process were not altered, including metalloproteinase enzymes (MMP) and tissue inhibitors of metalloproteinase enzymes (TIMP)
These observational data support the hypothesis that diastolic heart failure may be the result of an aggressive uncontrolled myocardial fibrotic process. The purpose of this project is to assess whether aldosterone inhibition or statin therapy may have an impact on increased levels of collagen markers, and thereby have a positive influence on parameters of diastolic function. Aldosterone is known to be a potent stimulus of the fibrotic process and therefore is a likely contributor. Support for this hypothesis comes from the observation in the systolic heart failure population where the administration of an aldosterone antagonist was found to be of benefit especially in those individuals who had serum evidence of heightened fibrotic activity. Statin therapy has been shown to reduce myocardial fibrosis in a rat model. Furthermore, preliminary data presented from the EPHESUS study has shown that greater benefits of eplerenone in those receiving concomitant statin therapy. We therefore propose to analyse the impact of atorvastatin therapy or aldosterone inhibition on markers of collagen turnover and also indices of diastolic function and markers of clinical well being.
We therefore propose to analyse the impact of aldosterone inhibition or statin therapy on markers of collagen turnover and also indices of diastolic function and markers of clinical well being.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: EplerenoneEplerenone |
| 3 | Active comparator | Other: No additional treatmentno additional treatment |
| 2 | Experimental | Drug: AtorvastatinAtorvastatin |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (2 listed)
- Patients with diastolic heart failure.
- Diastolic heart failure is defined as symptoms of heart failure with an ejection fraction >45%, BNP >100pg/ml and Doppler evidence of diastolic dysfunction.
Key exclusion criteria (4 listed)
- Clinically unstable as defined by any change in diuretic dose in the month prior to enrolment.
- Evidence of significant inflammatory disease or hepatic disease or metabolic bone disease which may alter parameters of collagen metabolism.
- Patients already receiving statin, aldosterone or eplerenone therapy
- Pregnant women and women of child bearing age
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 |
|---|---|---|
| EplerenoneAlso: Inspraoral Eplerenone titrated to 50mg for duration of 12 months | Drug | 1 |
| No additional treatmentnormal disease modifying therapy for heart failure i.e. ACE-I, beta blockers | Other | 3 |
| AtorvastatinAlso: Lipitororal Atorvastatin 40mg | Drug | 2 |
Primary outcome
To investigate the impact of aldosterone antagonism or statin therapy on markers of collagen turnover in patients with diastolic heart failure.
Time frame: 12 months
3 secondary outcomes
To assess the impact of aldosterone antagonism or statin therapy on markers of diastolic dysfunction by echocardiography
Time frame: 12 months
To assess the impact of aldosterone antagonism or statin therapy on indices of clinical well being
Time frame: 12 months
The assess the impact of aldosterone antagonism or statin therapy on diastolic indices by cardiac MRI
Time frame: 12 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Feb 2009.
- Derived from this study: PubMed 19850207Mak GJ, Ledwidge MT, Watson CJ, Phelan DM, Dawkins IR, Murphy NF, Patle AK, Baugh JA, McDonald KM. Natural history of markers of collagen turnover in patients with early diastolic dysfunction and impact of eplerenone. J Am Coll Cardiol. 2009 Oct 27;54(18):1674-82. doi: 10.1016/j.jacc.2009.08.021.
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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.
Ken McDonald, MD FRCP study director
Heart Failure Unit, St Vincent's University Hospital
George Mak, MB MRCPI principal investigator
St Vincent's University Hospital, Ireland
Niamh Murphy, MD MRCPI principal investigator
St Vincent's University Hospital, Ireland
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Eplerenone, No additional treatment and Atorvastatin in people with Diastolic Heart Failure, run by St Vincent's University Hospital, Ireland at 1 site in Ireland.
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 4 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 11 Feb 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 Ireland. 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.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
To investigate the impact of aldosterone antagonism or statin therapy on markers of collagen turnover in patients with diastolic heart failure. (time frame: 12 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 NCT00505336, 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 11 Feb 2009.