Comparison of Eplerenone Versus Spironolactone in Heart Failure Patients With Glucose Intolerance or Type 2 Diabetes

NCT01586442 | Completed Phase 3 DMC

• 1 other identifier: WS1911307
• Study Type: interventional
• Target: 62
• Locations: 1 country
• Sites: 1

Brief Summary

In this proposal,the investigators will examine whether the selectivity of eplerenone for the MR will translate into a better glucose and metabolic profile compare to spironolactone in patients with HF with glucose intolerance or type 2 diabetes. In addition, the investigators will also compare the impact of these two agents on changes of concentrations of established prognostic biomarkers of neurohormonal activation and extracellular matrix turnover.

Conditions

Heart Failure; Type 2 Diabetes; Glucose Intolerance

Outcome Measures

Primary Outcomes (7)

• Glycated hemoglobin

  Change in glycated hemoglobin

  4 months

• Fasting glucose and lipid profile

  4 months

• Plasma insulin

  4 months

• Cortisol

  4 months

• Adiponectin

  4 months

• NT-proBNP

  4 months

• PIIINP

  4 months

Study Arms (2)

Spironolactone

ACTIVE COMPARATOR

spironolactone 12.5mg once daily titrated to 25mg once daily

Drug: Spironolactone

Eplerenone

EXPERIMENTAL

Eplerenone 25mg once daily titrated to 50mg once daily

Drug: Eplerenone

Interventions

Eplerenone DRUG

Eplerenone 25mg once daily titrated to 50 mg once daily for 4 months

Also known as: Inspra

Eplerenone

Spironolactone DRUG

Spironolactone 12,5mg daily titrated to 25mg once daily for 16 weeks

Also known as: Aldactone

Spironolactone

Eligibility Criteria

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

You may qualify if:

• Male or female at least 18 years old.
• Symptomatic HF corresponding to NYHA class II-IV symptoms for at least 4 weeks prior randomization.
• A diagnosis of 1) impaired glucose tolerance described as overnight fasting between blood glucose 5.6 and 6.9 mmol/L on two occasions; or 2) type 2 diabetes defined as overnight fasting between blood glucose of 7.0 mmol/L or more on two occasions; a HbA1c equal to or higher than 6.5% or more on two occasions; or as a history of type II diabetes treated with hypoglycemic agents.
• LVEF equal to or lower than 40% documented by, contrast ventriculography, magnetic resonance imaging, radionuclide ventriculography or quantitative echocardiography within the previous 12 months if no cardiac event occurred since the measurement of the LVEF. The most recent measurements should be used.
• Treatment with an optimal and stable dose of ACE inhibitor (or ARB) for at least 4 weeks prior to enrolment in the study. In addition, patients should be treated with a stable dose of beta-blockers for at least 4 weeks prior enrolment in the study. Patients incapable to tolerate bisoprolol, carvedilol or metoprolol will be allowed within the trial.
• Informed consent must be obtained before any study specific procedures are performed

You may not qualify if:

• Current treatment with a combination of an ARB, an ACE or a renin inhibitor.
• Type 1 diabetes
• Known intolerance or allergy to eplerenone or spironolactone, including gynecomastia with spironolactone.
• Estimated GFR \< 30 mL/min/1.73 m2 as calculated using the MDRD equation (Appendix 1).
• Current serum potassium higher than 5.0 mmol/L (higher than 5.0 mEq/L).
• Current symptomatic hypotension and/or systolic B.P. \< 90 mmHg.
• Persistent systolic or diastolic hypertension (systolic \> 170 mmHg or diastolic \> 100 mmHg despite use of antihypertensive therapy).
• HF secondary to any of the following conditions: hemodynamically significant primary stenotic valvular cardiomyopathy, isolated right sided CHF, non cardiac disease (e.g. uncorrected thyroid disease), pericardial disease, complex congenital heart disease, myocarditis.
• Decompensated heart failure described as hospitalization or I.V. administration of medication in emergency room or heart failure clinic within 4 weeks (ex.: diuretics, inotropes, vasodilatators)
• Current treatment with insulin
• Stroke, acute coronary syndrome, PCI within the last 4 weeks before randomization.
• Cardiac surgery within 3 months.
• Significant liver disease (ALT x 3 times limit of normal).
• Planned cardiac surgery expected to be performed within the next 6 months.
• Previous heart transplant or heart transplant expected to be performed within the next 6 months.

Sponsors & Collaborators

• Montreal Heart Institute: lead
• Pfizer: collaborator

Study Sites (1)

Montreal Heart Institute

Montreal, Quebec, H1T 1C8, Canada

Location

Related Publications (1)

• Korol S, White M, O'Meara E, Tournoux F, Racine N, Ducharme A, Rouleau JL, Liszkowski M, Mansour A, Jutras M, Guertin MC, Bernier M, Lavoie J, Leclair G, Neagoe PE, Chaar D, Sirois MG, de Denus S. A comparison of the effects of selective and non-selective mineralocorticoid antagonism on glucose homeostasis of heart failure patients with glucose intolerance or type II diabetes: A randomized controlled double-blind trial. Am Heart J. 2018 Oct;204:190-195. doi: 10.1016/j.ahj.2018.07.002. Epub 2018 Jul 10.

  PMID: 30097164 DERIVED

MeSH Terms

Conditions

Heart Failure; Diabetes Mellitus, Type 2; Glucose Intolerance

Interventions

Eplerenone; Spironolactone

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Hyperglycemia

Intervention Hierarchy (Ancestors)

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

Study Officials

• Michel White, MD

  Montreal Heart Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Michel White, MD, FRCP(C), FACC, FESC

Study Record Dates

• First Submitted: April 24, 2012
• First Posted: April 26, 2012
• Study Start: March 1, 2012
• Primary Completion: March 1, 2015
• Study Completion: July 29, 2018
• Last Updated: October 7, 2022

Record last verified: 2022-10

Locations

CA (1)