Aldosterone Antagonism in Diastolic Heart Failure

NCT00108251 | Completed Phase 4 DMC

• 1 other identifier: CLIN-010-03S
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

The primary purpose of this study is to determine whether eplerenone has a beneficial effect on improving exercise ability in patients with diastolic heart failure.

Conditions

Congestive Heart Failure; Diastole

Keywords

controlled clinical trial; Diastole; Echocardiography; exercise tolerance; Heart Failure, Congestive; Receptors, Aldosterone

Outcome Measures

Primary Outcomes (1)

• Change in Six Minute Walk Distance from baseline to 24 weeks after randomization

  change in six minute walk distance between the placebo and spironolactone group

  24 weeks

Secondary Outcomes (1)

• Change in left ventricular stiffness at 24 weeks, Change in other echocardiographic measures of diastolic dysfunction at 24 weeks, Change in levels of B-type natriuretic peptide (BNP) at 24 weeks; Change in quality of life at 24 weeks

  24 weeks

Study Arms (2)

1

PLACEBO COMPARATOR

placebo tablet

Drug: Eplerenone

2

EXPERIMENTAL

eplerenone tablets

Drug: Placebo

Interventions

Eplerenone DRUG

aldosterone receptor blocker

Also known as: Inspra

1

Placebo DRUG

matching placebo

2

Eligibility Criteria

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

You may qualify if:

• All patients must have DHF as defined by all 3 of the following criteria:
• i)Presence of clinical heart failure for greater than or equal to 2 months before the screening visit. At the time of enrollment they should have NYHA functional class II or III heart failure symptoms such as dyspnea, fatigue on exertion, paroxysmal nocturnal dyspnea, and orthopnea.
• ii)Left ventricular ejection fraction greater than or equal to 50% (by echo, radionuclide angiography or contrast angiography) within 2 months of screening iii) BNP (brain natriuretic peptide) greater than or equal to 62 pg/ml within 2 months of screening
• Patients euvolemic on clinical examination. If patients are not euvolemic, all attempts will be made to achieve a euvolemic state with change in diuretic doses prior to enrollment into the study
• Systolic blood pressure less than or equal to 150 mmHg and diastolic blood pressure less than or equal to 95 mmHg for 4 weeks prior to and at the time of enrollment
• Able to walk at least 50 m at the time of enrollment
• All patients will be required to be on ACE inhibitors or angiotensin receptor blockers for at least 4 weeks prior to enrollment

You may not qualify if:

• Patients requiring eplerenone or spironolactone for treatment of other comorbid illnesses, e.g. ascites due to cirrhosis. Also, patients with severe hepatic impairment will not be included.
• Contraindication to eplerenone therapy with creatinine \> 2.5 mg/dl or serum potassium \> 5.0 mEq/L or creatinine clearance \< 30 ml/min/1.73 m2 or intolerance to eplerenone or spironolactone in the past
• Significant valvular heart disease, pericardial disease or severe chronic lung disease with cor pulmonale, as the cause of symptoms and signs of CHF
• Patients with technically inadequate echocardiographic windows or patients with severe mitral annular calcification
• Unstable angina or MI within 4 weeks prior to enrollment
• Patient with severe peripheral vascular disease and claudication or other physical conditions that will limit the distance walked by them
• Pregnant or lactating females
• History of alcohol or substance abuse or history of repeated non-compliance with medications
• History of cancer within 3 years (other than resected cutaneous basal or squamous cell carcinoma)
• Participation in any other drug trial within 30 days prior to enrollment
• Inability to provide informed consent
• On drugs that are strong inhibitors of CYP3A4 such as ketoconazole, itraconazole, nefazodone, trolandeomycin, clarithromycin, ritonavir, nelfinavir etc.

Sponsors & Collaborators

• US Department of Veterans Affairs: lead

Study Sites (1)

Michael E DeBakey VA Medical Center

Houston, Texas, 77030, United States

Location

Related Publications (1)

• Deswal A, Richardson P, Bozkurt B, Mann DL. Results of the Randomized Aldosterone Antagonism in Heart Failure with Preserved Ejection Fraction trial (RAAM-PEF). J Card Fail. 2011 Aug;17(8):634-42. doi: 10.1016/j.cardfail.2011.04.007. Epub 2011 May 31.

  PMID: 21807324 RESULT

MeSH Terms

Conditions

Heart Failure; Heart Murmurs

Interventions

Eplerenone

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

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

Study Officials

• Anita Deswal, MD MPH MBBS

  Michael E. DeBakey VA Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 14, 2005
• First Posted: April 15, 2005
• Study Start: August 1, 2004
• Primary Completion: September 1, 2007
• Study Completion: October 1, 2007
• Last Updated: September 8, 2011

Record last verified: 2011-09

Locations

US (1)