Mineralocorticoid Receptor Antagonists (MRA) in Heart Failure (HF) and Loop Diuretic Resistance

NCT02585843 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: AAAO9102
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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.

Conditions

Heart Failure

Keywords

Heart Failure; Mineralocorticoid receptor antagonists; Loop diuretic resistance

Outcome Measures

Primary Outcomes (1)

• Change in Body Weight

  change in body weight measured in kilograms between weight at baseline and weight at 7 days

  7 days

Secondary Outcomes (4)

• Change in Estimated Jugular Venous Pressure (cmH2O)

  7 days

• Change in 6-minute Walk Test Distance (6MWT)

  7 days

• Change in Score on the Visual Analogue Scale (VAS)

  7 days

• Change From Baseline to Day 7 on the Seven-Level Likert Scale

  7 days

Study Arms (2)

High-dose

EXPERIMENTAL

Spironolactone 100mg: 100mg/day of spironolactone (2 capsules), PO (oral) for 7 days

Drug: Spironolactone 100mg

Standard of Care

ACTIVE COMPARATOR

Spironolactone 25mg: 25mg/day of spironolactone, PO (oral)

Drug: Spironolactone 25mg

Interventions

Spironolactone 100mg DRUG

2 capsules of study medication consist of 100mg, PO (oral) for 7 days

Also known as: Aldactone

High-dose

Spironolactone 25mg DRUG

25mg/day of spironolactone

Also known as: Aldactone

Standard of Care

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Columbia University: lead

Study Sites (1)

Columbia University Medical Center

New York, New York, 10032, United States

Location

MeSH Terms

Conditions

Heart Failure

Interventions

Canrenoic Acid; Spironolactone

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

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

Results Point of Contact

• Title: A. Reshad Garan
• Organization: Columbia University

arg2024@cumc.columbia.edu

(917) 374-3346

Study Officials

• Arthur R Garan, MD

  Columbia University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Medicine at the Columbia University Medic, Dept of Medicine Cardiology

Study Record Dates

• First Submitted: August 30, 2015
• First Posted: October 23, 2015
• Study Start: November 1, 2015
• Primary Completion: March 31, 2017
• Study Completion: March 31, 2017
• Last Updated: August 8, 2019
• Results First Posted: July 23, 2019

Record last verified: 2019-07

Locations

US (1)