Back to resultsMineralocorticoid Receptor Antagonists (MRA) in Heart Failure (HF) and Loop Diuretic Resistance
Primary Purpose
Heart Failure
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Spironolactone 100mg
Spironolactone 25mg
Sponsored by
About this trial
This is an interventional treatment trial for Heart Failure focused on measuring Heart Failure, Mineralocorticoid receptor antagonists, Loop diuretic resistance
Eligibility Criteria
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)
Sites / Locations
- Columbia University Medical Center
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
High-dose
Standard of Care
Arm Description
Spironolactone 100mg: 100mg/day of spironolactone (2 capsules), PO (oral) for 7 days
Spironolactone 25mg: 25mg/day of spironolactone, PO (oral)
Outcomes
Primary Outcome Measures
Change in Body Weight
change in body weight measured in kilograms between weight at baseline and weight at 7 days
Secondary Outcome Measures
Change in Estimated Jugular Venous Pressure (cmH2O)
Change in estimated jugular venous pressure by physical exam in cmH2O between baseline and 7 days
Change in 6-minute Walk Test Distance (6MWT)
At baseline and final visit. The 6MWT will be conducted per American Thoracic Society guidelines.
Change in Score on the Visual Analogue Scale (VAS)
Dyspnea will be assessed at baseline and at 7 days with the score on the visual analogue scale (VAS). The scores range from 0 (minimum) to 100 (maximum) with higher numbers representing improvements in dyspnea (i.e. better) and lower numbers representing worsening of dyspnea (i.e. worse).
Change From Baseline to Day 7 on the Seven-Level Likert Scale
Dyspnea will be assessed using a Seven-Level Likert Scale at baseline and the day 7 visit. The outcome measure will be reported as a difference between these two assessments (value at 7 days minus the value at baseline). The values on this scale range from 1 to 7 with higher numbers indicating overall better subjective assessment related to the symptom of dyspnea. Therefore, positive numbers represent an overall improvement in dyspnea during the study intervention and the higher (more positive) this difference is, the better the subject's relief of dyspnea at the conclusion of the study intervention.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02585843
Brief Title
Mineralocorticoid Receptor Antagonists (MRA) in Heart Failure (HF) and Loop Diuretic Resistance
Official Title
Pilot Study of Natriuretic Versus Standard Doses of Mineralocorticoid Receptor Antagonists in Heart Failure and Loop Diuretic Resistance in Outpatients
Study Type
Interventional
2. Study Status
Record Verification Date
July 2019
Overall Recruitment Status
Completed
Study Start Date
November 2015 (Actual)
Primary Completion Date
March 31, 2017 (Actual)
Study Completion Date
March 31, 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Columbia University
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
Detailed Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Heart Failure
Keywords
Heart Failure, Mineralocorticoid receptor antagonists, Loop diuretic resistance
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
20 (Actual)
8. Arms, Groups, and Interventions
Arm Title
High-dose
Arm Type
Experimental
Arm Description
Spironolactone 100mg: 100mg/day of spironolactone (2 capsules), PO (oral) for 7 days
Arm Title
Standard of Care
Arm Type
Active Comparator
Arm Description
Spironolactone 25mg: 25mg/day of spironolactone, PO (oral)
Intervention Type
Drug
Intervention Name(s)
Spironolactone 100mg
Other Intervention Name(s)
Aldactone
Intervention Description
2 capsules of study medication consist of 100mg, PO (oral) for 7 days
Intervention Type
Drug
Intervention Name(s)
Spironolactone 25mg
Other Intervention Name(s)
Aldactone
Intervention Description
25mg/day of spironolactone
Primary Outcome Measure Information:
Title
Change in Body Weight
Description
change in body weight measured in kilograms between weight at baseline and weight at 7 days
Time Frame
7 days
Secondary Outcome Measure Information:
Title
Change in Estimated Jugular Venous Pressure (cmH2O)
Description
Change in estimated jugular venous pressure by physical exam in cmH2O between baseline and 7 days
Time Frame
7 days
Title
Change in 6-minute Walk Test Distance (6MWT)
Description
At baseline and final visit. The 6MWT will be conducted per American Thoracic Society guidelines.
Time Frame
7 days
Title
Change in Score on the Visual Analogue Scale (VAS)
Description
Dyspnea will be assessed at baseline and at 7 days with the score on the visual analogue scale (VAS). The scores range from 0 (minimum) to 100 (maximum) with higher numbers representing improvements in dyspnea (i.e. better) and lower numbers representing worsening of dyspnea (i.e. worse).
Time Frame
7 days
Title
Change From Baseline to Day 7 on the Seven-Level Likert Scale
Description
Dyspnea will be assessed using a Seven-Level Likert Scale at baseline and the day 7 visit. The outcome measure will be reported as a difference between these two assessments (value at 7 days minus the value at baseline). The values on this scale range from 1 to 7 with higher numbers indicating overall better subjective assessment related to the symptom of dyspnea. Therefore, positive numbers represent an overall improvement in dyspnea during the study intervention and the higher (more positive) this difference is, the better the subject's relief of dyspnea at the conclusion of the study intervention.
Time Frame
7 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Arthur R Garan, MD
Organizational Affiliation
Columbia University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Columbia University Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
Undecided
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Mineralocorticoid Receptor Antagonists (MRA) in Heart Failure (HF) and Loop Diuretic Resistance
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