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

NCT02299726 | Withdrawn Phase 2 DMC

• 1 other identifier: 1R34HL118350-01A1
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Acute Heart Failure

Keywords

acute heart failure; MRA; emergency department

Outcome Measures

Primary Outcomes (1)

• Change in Potassium from baseline through 5 days

  5 days

Study Arms (2)

Active

EXPERIMENTAL

spironolactone

Drug: Spironolactone

Placebo

PLACEBO COMPARATOR

matching placebo to active study drug

Other: Placebo

Interventions

Spironolactone DRUG

Active

Placebo OTHER

Matching placebo

Placebo

Eligibility Criteria

• Age: 22 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Indiana University: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator
• Vanderbilt University: collaborator
• Wayne State University: collaborator

MeSH Terms

Conditions

Emergencies

Interventions

Spironolactone

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Lactones; Organic Chemicals; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: November 17, 2014
• First Posted: November 24, 2014
• Study Start: May 1, 2015
• Primary Completion: May 1, 2018
• Study Completion: November 1, 2018
• Last Updated: April 21, 2017

Record last verified: 2017-04