Official Title: “Aldosterone-Blockade Randomized Controlled Trial In CHF - Diastolic”

Heart failure causes significant morbidity and mortality and is the most rapidly increasing cardiovascular diagnosis in North America overall prevalence is estimated at 0.4% to 2.4%.

Recently, heart failure with a preserved ejection fraction (HFNEF) was found in up to 50% of patients with symptomatic heart failure. Many studies have demonstrated that HFNEF has a poor prognosis with a mortality rate of up to 8% per year and a 50% chance of needing to be admitted to hospital in the next year. There are no proven therapies for this type of heart failure.

Aldosterone blockers (these drugs block a hormone that is elevated in patients with heart failure) are used in other types of heart failure. Our goal is to see if this type of drug improves the function of the heart by looking at the thickness of the heart muscle using MRI.

Also we will measure the amount of tissue formation and breakdown in the heart. The trial will be done using both the drug and a placebo so that we can see what effects are due to the drug.

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Efficacy Study

Aldosterone antagonists have shown efficacy in systolic heart failure and in patients with post-myocardial infarction systolic dysfunction in three major randomized placebo controlled trials. Together these trials have demonstrated a reduction in mortality, hospitalization and a regression in left ventricular mass by MRI.

Primary Objective The primary objective of this study will be to assess the change in markers of collagen turnover and correlate this with specific measures of left ventricular mass regression and diastolic function on MRI after 4 months of aldosterone blockade.

Study Design and Methods This study is a double-blind, concealed allocation, randomized trial at the University of Alberta where patients with diastolic heart failure will be randomized to spironolactone or matching placebo for 4 months. Outcomes assessed include LV mass by MRI, collagen markers, other biomarkers, clinical outcomes, quality of life and exercise testing

Intervention(s) in this Clinical Trial

• Drug: Spironolactone
• Drug: Placebo

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 1
  • Spironolactone
• Placebo Comparator: 2

Primary Measures

• LVH
  • Time Frame: 4 months
    

Inclusion Criteria:

• 1. HF by Framingham criteria
• 2. At least one admission to hospital for HF within the last 180 days
• 3. New York Heart Association Class II thru IV
• 4. Echocardiographic criteria:At least moderate diastolic dysfunction, Ejection fraction
• >45%

Exclusion Criteria:

• 1. Creatinine clearance <40 mls/min/1.73m2
• 2. Potassium >5.0 mmol/L
• 3. Recent acute coronary syndrome in the prior 4 weeks
• 4. Planned revascularization, defibrillator or pacemaker in next 4 months
• 5. Known previous intolerance to aldosterone antagonist

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 90 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: University of Alberta

Overall Clinical Trial Officials and Contacts

Justin Ezekowitz, MBBCh MSc Principal Investigator University of Alberta  

Overall Contact: Justin Ezekowitz, MBBCh MSc 7804078719 jae2@ualberta.ca

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00523757

Study ID Number: UHF-G533000207

ClinicalTrials.gov Identifier: NCT00523757

Health Authority: Canada: Health Canada