Diastolic Heart FailurePhase 4NCT01944384
Impacts of Aldosterone Blockade on Myocardial Remodeling in Hypertensive Patients With Diastolic Failing Heart
A Phase 4 study testing aldactone in people with Diastolic Heart Failure, run by National Taiwan University Hospital.
Trial summary
Aim of study: The effects of aldosterone blockade on myocardial remodeling in hypertensive patients with diastolic failing heart remains unclarified. Background: Nearly half of patients with clinical heart failure (HF) have normal left ventricular ejection fraction (LVEF) who usually present with apparent diastolic… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Diastolic Heart Failure
- What is being tested?
- aldactone
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- No sites listed yet
- Study dates
- Aug 2010to Dec 2011
- Phase
- Phase 4
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- well-controlled hypertensive patients with diastolic HF defined as the presence of diastolic dysfunction, normal LVEF (> 50 %), and exertional dyspnea (≧ New York Heart Association functional class II) or other HF signs/symptoms fulfilled with the Framingham criteria despite optimal pharmacological therapy
Who cannot join
- secondary hypertension
- restrictive, constrictive or hypertrophic cardiomyopathy
- more than moderate (mitral or tricuspid regurgitant jet area/atrial area more than 20%; aortic regurgitant jet to the tip of the mitral valve leaflets) valvular heart diseases
- chronic atrial fibrillation
- usage of aldosterone antagonist within 3 months
- chronic pulmonary disease
Show all 9Show fewer
- myocardial infarction within 3 months or active ischemia needing revascularization
- LVEF less than 50% by echocardiography
- renal failure (serum creatinine concentration more than 2.0 mg/dL).
About this study
Aim of study: The effects of aldosterone blockade on myocardial remodeling in hypertensive patients with diastolic failing heart remains unclarified.
Background: Nearly half of patients with clinical heart failure (HF) have normal left ventricular ejection fraction (LVEF) who usually present with apparent diastolic dysfunction (DD) and are referred as diastolic HF (DHF). The renin-angiotensin-aldosterone system is an established major pathway that is operative in the pathogenesis of HF. The effects of aldosterone on myocardial hypertrophy, fibrosis and endothelial dysfunction have clearly been established in human and animal models. Furthermore, in these models, aldosterone antagonism prevented the development of myocardial fibrosis independent of its effect on blood pressure or myocardial hypertrophy. However, its application to patients with DHF is unspecified. In the study, we hypothesize that aldosterone blockade could reverse LV remodeling process in hypertensive patients with DHF.
Study protocol: We will enroll medically well-controlled hypertensive patients who have DHF defined as the presence of exertional dyspnea or HF signs/symptoms, diastolic dysfunction as impaired tissue-Doppler (TDI) derived mitral early annular diastolic velocity (< 8 cm/s), and LVEF > 50 % in echocardiography. All patients will be randomized to receive spironolactone 25 mg per day or not for at least 6 months. At baseline before randomization and 6 months after randomization, we will investigate the Quality-of-life (QOL) score by Minnesota Living with Heart Failure questionnaire (Chinese version), echocardiography coupled with TDI to assess the degree of LV hypertrophy, myocardial systolic and diastolic characteristics. Otherwise, we draw blood sampling at baseline and after randomization for quantifying and comparing several biomarkers which are currently proved to be correlated with LV hypertrophy, myocardial fibrosis, and biomechanical stretch in DHF patients, such as N-terminal pro-brain-type natriuretic peptide, matrix metalloproteinase-2, carboxy-terminal telopeptide, procollagen type III amino-terminal propeptide, soluble ST2, and galectin-3. Expected results: Aldosterone antagonism is effective for hypertensive patients with DHF by improving the quality of life, echo-derived myocardial function, and reducing ventricular mechanical stretch through lessening the degree of LV hypertrophy and myocardial fibrosis.
Read the detailed description
Aim of study: The effects of aldosterone blockade on myocardial remodeling in hypertensive patients with diastolic failing heart remains unclarified. Background: Nearly half of patients with clinical heart failure (HF) have normal left ventricular ejection fraction (LVEF) who usually present with apparent diastolic dysfunction (DD) and are referred as diastolic HF (DHF). Hypertensive heart disease occurs in the majority of patients with DHF, and several key aspects of heart failure secondary to hypertensive heart disease are the relatively highly prevalent LV hypertrophy, cardiac fibrosis, and endothelial dysfunction-mediated myocardial injury caused by changes in the local and systemic neurohormonal environment, and all of which are associated with LV diastolic dysfunction and tissue-Doppler derived systolic myocardial function. The renin-angiotensin-aldosterone system is an established major pathway that is operative in the pathogenesis of HF. The effects of aldosterone on myocardial hypertrophy, fibrosis and endothelial dysfunction have clearly been established in human and animal models. Furthermore, in these models, aldosterone antagonism prevented the development of myocardial fibrosis independent of its effect on blood pressure or myocardial hypertrophy. However, its application to patients with DHF is unspecified. In the study, we hypothesize that aldosterone blockade could reverse LV remodeling process in hypertensive patients with DHF.
Study protocol: We will enroll medically well-controlled hypertensive patients who have DHF defined as the presence of exertional dyspnea or HF signs/symptoms, diastolic dysfunction as impaired tissue-Doppler (TDI) derived mitral early annular diastolic velocity (< 8 cm/s), and LVEF > 50 % in echocardiography. All patients will be randomized to receive spironolactone 25 mg per day or not for at least 6 months. At baseline before randomization and 6 months after randomization, we will investigate the Quality-of-life (QOL) score by Minnesota Living with Heart Failure questionnaire (Chinese version), echocardiography coupled with TDI to assess the degree of LV hypertrophy, myocardial systolic and diastolic characteristics. Otherwise, we draw blood sampling at baseline and after randomization for quantifying and comparing several biomarkers which are currently proved to be correlated with LV hypertrophy, myocardial fibrosis, and biomechanical stretch in DHF patients, such as N-terminal pro-brain-type natriuretic peptide, matrix metalloproteinase-2, carboxy-terminal telopeptide, procollagen type III amino-terminal propeptide, soluble ST2, and galectin-3. Expected results: Aldosterone antagonism is effective for hypertensive patients with DHF by improving the quality of life, echo-derived myocardial function, and reducing ventricular mechanical stretch through lessening the degree of LV hypertrophy and myocardial fibrosis.
- Conditions
- Diastolic Heart Failure
- Being tested
- aldactone
- 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.
aldactoneDrug
aldactone 25 mg for 6 months
| Study group | Role | What they receive |
|---|---|---|
| aldactone | Experimental | aldactone 25 mg for 6 months Receives: Drug: aldactone |
| without aldactone | No intervention | Not described |
What is being measured
The primary outcome is the main question the study is designed to answer.
peak myocardial velocity (Sm) during the ejection phase over the 6-basal segments
Measured: 6 months
Secondary outcomes (6)
pro-brain natriuretic peptide (proBNP)
Measured: 6 months
matrix metalloproteinase-2 (MMP-2)
Measured: 6 months
matrix metalloproteinase-9 (MMP-9), etc.
Measured: 6 months
carboxy-terminal telopeptide of collagen I(ICTP)
Measured: 6 months
procollagen type III amino-terminal propeptide (PIIINP)
Measured: 6 months
soluble ST2 receptor (sST2)
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 posted17 Sep 2013 (estimated)
- Study startAug 2010
- Primary completionDec 2010
- Study completionDec 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Diastolic Heart FailureStudies of the same condition, open and under way.
- More trials run by National Taiwan University HospitalThe 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Taiwan University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Wang Yi Chih, MD, PhD, Principal investigator, NTUH
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01944384
- Sponsor's protocol ID
- 200912097M
- Status last verified
- Sep 2013
- First submitted
- 4 Sep 2013
- Last updated
- 17 Sep 2013
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Sep 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Impacts of Aldosterone Blockade on Myocardial Remodeling in Hypertensive Patients With Diastolic Failing Heart
- ClinicalTrials.gov ID
- NCT01944384
- Acronym / sponsor ID
- 200912097M
- Conditions
- Diastolic Heart Failure
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- National Taiwan University HospitalUniversity, hospital or other
- Study start
- Aug 2010
- Primary completion
- Dec 2010 (actual)
- Study completion
- Dec 2011 (actual)
- First posted
- 17 Sep 2013 (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.
Aim of study: The effects of aldosterone blockade on myocardial remodeling in hypertensive patients with diastolic failing heart remains unclarified.
Background: Nearly half of patients with clinical heart failure (HF) have normal left ventricular ejection fraction (LVEF) who usually present with apparent diastolic dysfunction (DD) and are referred as diastolic HF (DHF). The renin-angiotensin-aldosterone system is an established major pathway that is operative in the pathogenesis of HF. The effects of aldosterone on myocardial hypertrophy, fibrosis and endothelial dysfunction have clearly been established in human and animal models. Furthermore, in these models, aldosterone antagonism prevented the development of myocardial fibrosis independent of its effect on blood pressure or myocardial hypertrophy. However, its application to patients with DHF is unspecified. In the study, we hypothesize that aldosterone blockade could reverse LV remodeling process in hypertensive patients with DHF.
Study protocol: We will enroll medically well-controlled hypertensive patients who have DHF defined as the presence of exertional dyspnea or HF signs/symptoms, diastolic dysfunction as impaired tissue-Doppler (TDI) derived mitral early annular diastolic velocity (< 8 cm/s), and LVEF > 50 % in echocardiography. All patients will be randomized to receive spironolactone 25 mg per day or not for at least 6 months. At baseline before randomization and 6 months after randomization, we will investigate the Quality-of-life (QOL) score by Minnesota Living with Heart Failure questionnaire (Chinese version), echocardiography coupled with TDI to assess the degree of LV hypertrophy, myocardial systolic and diastolic characteristics. Otherwise, we draw blood sampling at baseline and after randomization for quantifying and comparing several biomarkers which are currently proved to be correlated with LV hypertrophy, myocardial fibrosis, and biomechanical stretch in DHF patients, such as N-terminal pro-brain-type natriuretic peptide, matrix metalloproteinase-2, carboxy-terminal telopeptide, procollagen type III amino-terminal propeptide, soluble ST2, and galectin-3. Expected results: Aldosterone antagonism is effective for hypertensive patients with DHF by improving the quality of life, echo-derived myocardial function, and reducing ventricular mechanical stretch through lessening the degree of LV hypertrophy and myocardial fibrosis.
Detailed description
Aim of study: The effects of aldosterone blockade on myocardial remodeling in hypertensive patients with diastolic failing heart remains unclarified. Background: Nearly half of patients with clinical heart failure (HF) have normal left ventricular ejection fraction (LVEF) who usually present with apparent diastolic dysfunction (DD) and are referred as diastolic HF (DHF). Hypertensive heart disease occurs in the majority of patients with DHF, and several key aspects of heart failure secondary to hypertensive heart disease are the relatively highly prevalent LV hypertrophy, cardiac fibrosis, and endothelial dysfunction-mediated myocardial injury caused by changes in the local and systemic neurohormonal environment, and all of which are associated with LV diastolic dysfunction and tissue-Doppler derived systolic myocardial function. The renin-angiotensin-aldosterone system is an established major pathway that is operative in the pathogenesis of HF. The effects of aldosterone on myocardial hypertrophy, fibrosis and endothelial dysfunction have clearly been established in human and animal models. Furthermore, in these models, aldosterone antagonism prevented the development of myocardial fibrosis independent of its effect on blood pressure or myocardial hypertrophy. However, its application to patients with DHF is unspecified. In the study, we hypothesize that aldosterone blockade could reverse LV remodeling process in hypertensive patients with DHF.
Study protocol: We will enroll medically well-controlled hypertensive patients who have DHF defined as the presence of exertional dyspnea or HF signs/symptoms, diastolic dysfunction as impaired tissue-Doppler (TDI) derived mitral early annular diastolic velocity (< 8 cm/s), and LVEF > 50 % in echocardiography. All patients will be randomized to receive spironolactone 25 mg per day or not for at least 6 months. At baseline before randomization and 6 months after randomization, we will investigate the Quality-of-life (QOL) score by Minnesota Living with Heart Failure questionnaire (Chinese version), echocardiography coupled with TDI to assess the degree of LV hypertrophy, myocardial systolic and diastolic characteristics. Otherwise, we draw blood sampling at baseline and after randomization for quantifying and comparing several biomarkers which are currently proved to be correlated with LV hypertrophy, myocardial fibrosis, and biomechanical stretch in DHF patients, such as N-terminal pro-brain-type natriuretic peptide, matrix metalloproteinase-2, carboxy-terminal telopeptide, procollagen type III amino-terminal propeptide, soluble ST2, and galectin-3. Expected results: Aldosterone antagonism is effective for hypertensive patients with DHF by improving the quality of life, echo-derived myocardial function, and reducing ventricular mechanical stretch through lessening the degree of LV hypertrophy and myocardial fibrosis.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| aldactone | Experimental | Drug: aldactonealdactone 25 mg for 6 months |
| without aldactone | No intervention | – |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- well-controlled hypertensive patients with diastolic HF defined as the presence of diastolic dysfunction, normal LVEF (> 50 %), and exertional dyspnea (≧ New York Heart Association functional class II) or other HF signs/symptoms fulfilled with the Framingham criteria despite optimal pharmacological therapy
Key exclusion criteria (9 listed)
- secondary hypertension
- restrictive, constrictive or hypertrophic cardiomyopathy
- more than moderate (mitral or tricuspid regurgitant jet area/atrial area more than 20%; aortic regurgitant jet to the tip of the mitral valve leaflets) valvular heart diseases
- chronic atrial fibrillation
- usage of aldosterone antagonist within 3 months
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 |
|---|---|---|
| aldactonealdactone 25 mg for 6 months | Drug | aldactone |
Primary outcome
peak myocardial velocity (Sm) during the ejection phase over the 6-basal segments
Time frame: 6 months
6 secondary outcomes
pro-brain natriuretic peptide (proBNP)
Time frame: 6 months
matrix metalloproteinase-2 (MMP-2)
Time frame: 6 months
matrix metalloproteinase-9 (MMP-9), etc.
Time frame: 6 months
carboxy-terminal telopeptide of collagen I(ICTP)
Time frame: 6 months
procollagen type III amino-terminal propeptide (PIIINP)
Time frame: 6 months
soluble ST2 receptor (sST2)
Time frame: 6 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 17 Sep 2013.
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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.
Wang Yi Chih, MD, PhD principal investigator
NTUH
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing aldactone in people with Diastolic Heart Failure, run by National Taiwan University Hospital.
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 1 inclusion and 9 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 17 Sep 2013. Status can change between updates, so confirm with the study contact before making plans.
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?
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?
peak myocardial velocity (Sm) during the ejection phase over the 6-basal segments (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 17 Sep 2013.