Trial record 2 of 13 for:    mineralocorticoid antagonism

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

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by Montreal Heart Institute
Sponsor:
Collaborator:
Pfizer
Information provided by (Responsible Party):
Michel White, Montreal Heart Institute
ClinicalTrials.gov Identifier:
NCT01586442
First received: April 24, 2012
Last updated: May 13, 2014
Last verified: May 2014
  Purpose

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.


Condition Intervention Phase
Heart Failure
Type 2 Diabetes
Glucose Intolerance
Drug: Eplerenone
Drug: Spironolactone
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Comparison of the Effects of Selective and Non Selective Mineralocorticoid Antagonism on Glucose Homeostasis and Lipid Profile of Heart Failure Patients With Glucose Intolerance or Type 2 Diabetes.

Resource links provided by NLM:


Further study details as provided by Montreal Heart Institute:

Primary Outcome Measures:
  • Glycated hemoglobin [ Time Frame: 4 months ] [ Designated as safety issue: No ]
    Change in glycated hemoglobin

  • Fasting glucose and lipid profile [ Time Frame: 4 months ] [ Designated as safety issue: No ]
  • Plasma insulin [ Time Frame: 4 months ] [ Designated as safety issue: No ]
  • Cortisol [ Time Frame: 4 months ] [ Designated as safety issue: No ]
  • Adiponectin [ Time Frame: 4 months ] [ Designated as safety issue: No ]
  • NT-proBNP [ Time Frame: 4 months ] [ Designated as safety issue: No ]
  • PIIINP [ Time Frame: 4 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 62
Study Start Date: March 2012
Estimated Study Completion Date: July 2015
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Spironolactone
spironolactone 12.5mg once daily titrated to 25mg once daily
Drug: Spironolactone
Spironolactone 12,5mg daily titrated to 25mg once daily for 16 weeks
Other Name: Aldactone
Experimental: Eplerenone
Eplerenone 25mg once daily titrated to 50mg once daily
Drug: Eplerenone
Eplerenone 25mg once daily titrated to 50 mg once daily for 4 months
Other Name: Inspra

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male or female at least 18 years old.
  2. Symptomatic HF corresponding to NYHA class II-IV symptoms for at least 4 weeks prior randomization.
  3. 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.
  4. 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.
  5. 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.
  6. Informed consent must be obtained before any study specific procedures are performed

Exclusion Criteria:

  1. Current treatment with a combination of an ARB, an ACE or a renin inhibitor.
  2. Type 1 diabetes
  3. Known intolerance or allergy to eplerenone or spironolactone, including gynecomastia with spironolactone.
  4. Estimated GFR < 30 mL/min/1.73 m2 as calculated using the MDRD equation (Appendix 1).
  5. Current serum potassium higher than 5.0 mmol/L (higher than 5.0 mEq/L).
  6. Current symptomatic hypotension and/or systolic B.P. < 90 mmHg.
  7. Persistent systolic or diastolic hypertension (systolic > 170 mmHg or diastolic > 100 mmHg despite use of antihypertensive therapy).
  8. 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.
  9. 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)
  10. Current treatment with insulin
  11. Stroke, acute coronary syndrome, PCI within the last 4 weeks before randomization.
  12. Cardiac surgery within 3 months.
  13. Significant liver disease (ALT x 3 times limit of normal).
  14. Planned cardiac surgery expected to be performed within the next 6 months.
  15. Previous heart transplant or heart transplant expected to be performed within the next 6 months.
  16. Presence of any non-cardiac diseases likely to significantly shorten life expectancy to < 1 year.
  17. Pregnant or lactating women or women of childbearing potential who are not protected from pregnancy by an accepted method of contraception, such as the oral contraceptive pill, an intrauterine device or surgical sterilization (all women of childbearing potential must have a negative pregnancy test before randomization).
  18. Any condition that in the opinion of the investigator would jeopardize the evaluation on efficacy or safety or be associated with poor adherence to the protocol.
  19. Treatment with any investigational agent or device within 4 weeks of randomization.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01586442

Locations
Canada, Quebec
Montreal Heart Institute Recruiting
Montreal, Quebec, Canada, H1T 1C8
Contact: Hélène Brown, RN, B.Sc    514-376-3330 ext 3931    helene.brown@icm-mhi.org   
Sponsors and Collaborators
Montreal Heart Institute
Pfizer
Investigators
Principal Investigator: Michel White, MD Montreal Heart Institute
  More Information

No publications provided

Responsible Party: Michel White, Michel White, MD, FRCP(C), FACC, FESC, Montreal Heart Institute
ClinicalTrials.gov Identifier: NCT01586442     History of Changes
Other Study ID Numbers: WS1911307
Study First Received: April 24, 2012
Last Updated: May 13, 2014
Health Authority: Canada: Health Canada

Additional relevant MeSH terms:
Mineralocorticoid Receptor Antagonists
Heart Failure
Diabetes Mellitus, Type 2
Glucose Intolerance
Diabetes Mellitus
Heart Diseases
Cardiovascular Diseases
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Hyperglycemia
Spironolactone
Eplerenone
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Diuretics, Potassium Sparing
Diuretics
Natriuretic Agents
Cardiovascular Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on September 16, 2014