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

Primary Purpose

Acute Heart Failure

Status

Withdrawn

Phase

Phase 2

Locations

Study Type

Interventional

Intervention

Spironolactone

Placebo

About this trial

This is an interventional treatment trial for Acute Heart Failure focused on measuring acute heart failure, MRA, emergency department

Eligibility Criteria

22 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Active

Placebo

Arm Description

spironolactone

matching placebo to active study drug

Outcomes

Primary Outcome Measures

Change in Potassium from baseline through 5 days

Secondary Outcome Measures

Full Information

NCT ID

NCT02299726

First Posted

November 17, 2014

Last Updated

April 19, 2017

Sponsor

Indiana University

Collaborators

National Heart, Lung, and Blood Institute (NHLBI), Vanderbilt University, Wayne State University

1. Study Identification

Unique Protocol Identification Number

NCT02299726

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

April 2017

Overall Recruitment Status

Withdrawn

Why Stopped

Study was not funded

Study Start Date

May 2015 (undefined)

Primary Completion Date

May 2018 (Anticipated)

Study Completion Date

November 2018 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Indiana University

Collaborators

National Heart, Lung, and Blood Institute (NHLBI), Vanderbilt University, Wayne State University

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

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

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Acute Heart Failure

Keywords

acute heart failure, MRA, emergency department

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

0 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Active

Arm Type

Experimental

Arm Description

spironolactone

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

matching placebo to active study drug

Intervention Type

Drug

Intervention Name(s)

Spironolactone

Intervention Type

Other

Intervention Name(s)

Placebo

Intervention Description

Matching placebo

Primary Outcome Measure Information:

Title

Change in Potassium from baseline through 5 days

Time Frame

5 days

10. Eligibility

Sex

All

Minimum Age & Unit of Time

22 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

12. IPD Sharing Statement

Learn more about this trial

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

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