Aldosterone Blockade in Heart Failure

Phase 3

Completed

• Conditions: Heart Failure
• Interventions: Drug: Placebo; Drug: Spironolactone

• Registration Number: NCT00523757
• Lead Sponsor: Justin Ezekowitz

Brief Summary

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.

Detailed Description

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

Study Timeline

• Study Start: 2007-08
• Study First Submitted: 2007-08-29
• Study First Submitted QC: 2007-08-29
• Study First Posted: 2007-08-31
• Primary Completion: 2010-04-30
• Study Completion: 2010-04-30
• Status Verified: 2018-11
• Last Update Submitted: 2018-11-05
• Last Update Posted: 2018-11-07

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 8

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
2	Placebo	-
1	Spironolactone	Spironolactone

Primary Outcome Measures

Name	Time	Method
LVH	4 months

Trial Locations

Locations (1)

University of Alberta Hospital; 🇨🇦 Edmonton, Alberta, Canada