Early Aldosterone Blockade in Acute Heart Failure: An Exploratory Safety Study

Study Overview
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Brief Summary
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Over one million hospitalizations for acute heart failure (AHF) occur over every year in the United States, resulting in high mortality, re-hospitalizations, and incurred financial costs; yet nearly every attempt over the last 10 years to improve outcomes with novel therapies have all failed. In this proposal, we will study whether a generic drug known as a mineralocorticoid receptor antagonist (more commonly known as an aldosterone blocker), proven to reduce morbidity and mortality for chronic heart failure patients, is safe and feasible to give to AHF patients in the emergency department and during hospitalization for a total of 3 days. The results of this study will provide necessary and sufficient data to design an efficacy study in a larger population to test whether early use of a high-dose of mineralocorticoid receptor antagonists will reduce post-discharge morbidity and mortality.

Detailed Description
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This clinical trial pilot study - Early Aldosterone Blockade in Acute Heart Failure: An Exploratory Safety Study - will explore the safety of early mineralocorticoid receptor blockade with high-dose spironolactone (100mg/daily), an oral mineralocorticoid receptor antagonist, versus placebo (both in addition to standard therapy), in patients admitted with acute heart failure (AHF) for 3 days. Aim 1 will answer the critical question that early mineralocorticoid receptor (MR) antagonism in AHF patients is sufficiently safe to move forward with a definitive trial. Aim 2 will demonstrate feasibility of patient enrollment and compliance with treatment throughout the study to inform future study design and enrollment projections. This study will provide the necessary and sufficient data in order to plan a larger, simple, definitive trial to test the hypothesis that early aldosterone blockade in AHF patients will reduce mortality and 30-day readmissions. The primary endpoint for the pilot study will be the difference in incidence of mean change of serum potassium of a specific amount from baseline to 120 hours from initial dose between placebo vs. spironolactone treated subjects.

Official Title
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Early Aldosterone Blockade in Acute Heart Failure: An Exploratory Safety Study

Conditions
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Acute Heart Failure

Intervention / Treatment
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* Drug: Spironolactone
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: • Male or female, age ≥ 21 years Primary reason for admission is acute heart failure requiring IV loop diuretic therapy either in the emergency department (ED) or within 6 hours after direct hospital admission. Enrolled within 12 hours of first dose of IV loop diuretic therapy BNP > 300 pg/mL and/or NT-ProBNP > 1200 pg/mL by local laboratory At least 1 of the following: Jugular Venous Distention, Peripheral edema, Radiographic evidence of pulmonary congestion Ejection Fraction ≤ 40% within past 12 months by any method Able to take oral medications Able to provide written informed consent Agrees to a minimum of 3 blood draws up to 72 hours from randomization Exclusion Criteria: • Potassium ≥ 4.8mEq eGFR (by sMDRD) < 45 ml/min/1.73 m2 or a worsening by 50% or more compared to any measurement in the last 6 months or planned ultrafiltration History of or planned organ transplantation of any kind within the next 90 days Invasive mechanical ventilatory support (non-invasive positive pressure ventilation is allowed) Cardiogenic shock and/or treatment or planned treatment with inotropic or vasopressor medications (e.g. dobutamine, dopamine, milrinone, norepinephrine) or intra-aortic balloon pump Refractory, end-stage HF defined as subjects who are appropriate candidates for specialized treatment strategies, such as transplant, ventricular assist devices, continuous intravenous inotropic therapy, or hospice care Co-morbid condition with an expected survival <6 months or active cancer History of stroke, cardiac surgery, or ACS currently or within past 60 days Temperature ≥101.5 degrees F Severe valvular or liver disease On digoxin or history of MRA allergy or adverse drug reaction Women who are currently pregnant or report a recent pregnancy (last 60 days) or plan on becoming pregnant during the next 4 months Participation in another drug or device trial in which the last dose of drug was within the past 30 days or an investigational medical device has been implanted

Ages Eligible for Study
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Minimum Age: 22 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Active<br>spironolactone | Drug: Spironolactone<br> <br> |
| Placebo Comparator: Placebo<br>matching placebo to active study drug | Other: Placebo<br>* Matching placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Potassium from baseline through 5 days |  | 5 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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acute heart failure, MRA, emergency department