Mineralocorticoid Receptor Antagonists (MRA) in Heart Failure (HF) and Loop Diuretic Resistance
| Status: | Recruiting |
|---|---|
| Conditions: | Cardiology |
| Therapuetic Areas: | Cardiology / Vascular Diseases |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 4/21/2016 |
| Start Date: | November 2015 |
| End Date: | September 2016 |
| Contact: | Amirali Masoumi, MD |
| Email: | am4052@cumc.columbia.edu |
| Phone: | (212) 305-9264 |
Pilot Study of Natriuretic Versus Standard Doses of Mineralocorticoid Receptor Antagonists in Heart Failure and Loop Diuretic Resistance in Outpatients
This is a prospective, single-center, double-blind and randomized placebo controlled trial
for evaluation of a 7-day 100mg daily dose of spironolactone on weight loss and resolution
of signs and symptoms of congestion in outpatients with acute decompensated heart failure
(ADHF). Patients who are not responding to their current loop diuretics will be considered
for this study. Mineralocorticoid receptor antagonists (MRAs) are recommended as standard of
care in management of heart failure (HF) patients. However, recommended doses of MRAs
(spironolactone 25mg/daily or eplerenone 50mg/daily) will not have any impact on signs and
symptoms of volume overload. Therefore, the proposed study will aim to show the impact of
this outpatient regimen to improve diuresis and possible reduction in hospitalization for
further diuretic management in HF patients with signs and symptoms of congestion.
for evaluation of a 7-day 100mg daily dose of spironolactone on weight loss and resolution
of signs and symptoms of congestion in outpatients with acute decompensated heart failure
(ADHF). Patients who are not responding to their current loop diuretics will be considered
for this study. Mineralocorticoid receptor antagonists (MRAs) are recommended as standard of
care in management of heart failure (HF) patients. However, recommended doses of MRAs
(spironolactone 25mg/daily or eplerenone 50mg/daily) will not have any impact on signs and
symptoms of volume overload. Therefore, the proposed study will aim to show the impact of
this outpatient regimen to improve diuresis and possible reduction in hospitalization for
further diuretic management in HF patients with signs and symptoms of congestion.
The incidence and prevalence of heart failure (HF) is rising with more than 5 million
Americans suffering from this syndrome. Hospitalization rates for acute decompensated heart
failure (ADHF) are also remarkably high, exceeding more than 1 million admissions per year.
Congestion is the main cause of hospitalization for ADHF. Loop diuretics as the main therapy
for decongestion, often are not adequate since many patients with ADHF develop "loop
diuretic resistance". These patients will require hospitalization for intravenous diuretic
or other advanced decongestion therapies. Thus, novel decongestion therapies are needed to
decrease hospital admission rates and subsequent complications of multiple hospitalizations.
Hyperaldosteronism, not only is a pivotal pathogenic factor in HF, but also contributes to
loop diuretic resistance. Attempts for normalization of circulatory aldosterone with
mineralocorticoid receptor antagonists (MRAs), mainly spironolactone, have shown to decrease
mortality in HF patients with reduced left ventricular ejection fraction (LVEF). Moreover,
MRAs significantly decrease the rate of rehospitalization in both HF with preserved and
reduced LVEF. The dose of spironolactone in these trials is 25mg daily. However, this dose
does not increase natriuresis (urinary sodium excretion). Natriuresis is achieved with
higher doses of MRAs. Therefore, the primary aim of this study is to examine the efficacy of
7-day 100mg daily of spironolactone on weight loss and resolution of signs and symptoms of
congestion in patients aged 60 years with ADHF and loop diuretic resistance.
Americans suffering from this syndrome. Hospitalization rates for acute decompensated heart
failure (ADHF) are also remarkably high, exceeding more than 1 million admissions per year.
Congestion is the main cause of hospitalization for ADHF. Loop diuretics as the main therapy
for decongestion, often are not adequate since many patients with ADHF develop "loop
diuretic resistance". These patients will require hospitalization for intravenous diuretic
or other advanced decongestion therapies. Thus, novel decongestion therapies are needed to
decrease hospital admission rates and subsequent complications of multiple hospitalizations.
Hyperaldosteronism, not only is a pivotal pathogenic factor in HF, but also contributes to
loop diuretic resistance. Attempts for normalization of circulatory aldosterone with
mineralocorticoid receptor antagonists (MRAs), mainly spironolactone, have shown to decrease
mortality in HF patients with reduced left ventricular ejection fraction (LVEF). Moreover,
MRAs significantly decrease the rate of rehospitalization in both HF with preserved and
reduced LVEF. The dose of spironolactone in these trials is 25mg daily. However, this dose
does not increase natriuresis (urinary sodium excretion). Natriuresis is achieved with
higher doses of MRAs. Therefore, the primary aim of this study is to examine the efficacy of
7-day 100mg daily of spironolactone on weight loss and resolution of signs and symptoms of
congestion in patients aged 60 years with ADHF and loop diuretic resistance.
Inclusion Criteria:
- History of heart failure with either reduced or preserved ejection fraction for 3
months
- Patients with New York Heart Association (NYHA) class II- IV heart failure symptoms,
with at least one worsening symptom (Dyspnea on exertion, shortness of breath,
orthopnea, early satiety) and one sign of congestion (pulmonary rales, elevated
jugular venous pressure10cmHg, peripheral edema and ascites)
- Decision by primary cardiologist or heart failure (HF) specialist to increase the
home diuretic dose
- Stable treatment with beta-blockers for 1 month unless contraindicated (i.e.
intolerance, bradycardia) as specified by primary cardiologist/HF provider
- Stable treatment with angiotensin converting enzyme-1 (ACE-1) or angiotensin receptor
blocker (ARB) for 1 month
- Spironolactone dose 25mg or eplerenone 50mg per day
- Daily furosemide or furosemide equivalent dose of 80mg or greater
- Serum potassium concentration 4.5 mmol/L or 5.0 mmol/L if on potassium supplements
- Estimated Glomerular Filtration Rate (eGFR) by Modification of Diet in Renal Disease
(MDRD) equation 40 ml/min/1.73
Exclusion Criteria:
- Inability to complete informed consent form
- Allergy or intolerance to spironolactone
- Systolic blood pressure <100 mmHg
- Patient in need of hospitalization per cardiologist decision
- Current inotrope dependency
- Current mechanical circulatory support
- Acute coronary syndromes or unstable angina within the past 4 weeks
- History of cardiac transplant
- Obstructive cardiac valvular disease
- Primary hypertrophic cardiomyopathy, infiltrative cardiomyopathy
- Significant ventricular arrhythmia necessitating defibrillator therapy within the
past 14 days
- Atrioventricular conduction abnormality greater than first-degree block
- Primary liver disease resulted in cirrhosis or abnormal liver function tests
(transaminases and alkaline phosphatase levels 3 times the upper limit of normal
- Acute malignancy
- Active infection requiring antimicrobial treatment (Suppression antimicrobial for
chronic infections are exempt)
We found this trial at
1
site
Columbia University Medical Center Situated on a 20-acre campus in Northern Manhattan and accounting for...
Click here to add this to my saved trials
