Effects of Aliskiren on Patient With Heart Failure and a Normal Ejection Fraction

Condition(s) targeted: Heart Failure

Intervention: aliskiren (Drug); placebo (Drug)

Phase: Phase 4

Status: Recruiting

Sponsored by: Wake Forest University

Official(s) and/or principal investigator(s):
Dalane W Kitzman, MD, Principal Investigator, Affiliation: Wake Forest University

Overall contact:
Dalane W Kitzman, MD, Phone: 336-716-3274, Ext: 6-3274, Email: dkitzman@wfubmc.edu

The primary objective of this study is to determine whether treatment with aliskiren (300 mg) compared to placebo will improve treadmill exercise time in older (age ≥ 55 years) patients with heart failure and normal ejection fraction (HFNEF).

Official title: A Randomized, Blinded, Placebo-Controlled Six Month Treatment Trial of Aliskiren to Improve Exercise Tolerance in Older Patients With Heart Failure and Normal Ejection Fraction

Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Primary outcome: The primary objective of this study is to determine whether treatment with aliskiren (300 mg) compared to placebo will improve treadmill exercise time in older (age ≥ 55 years) patients with heart failure and normal ejection fraction (HFNEF).

Secondary outcome:

Determine whether aliskiren (300mg) compared to placebo will improve other measures of exercise performance, including peak exercise oxygen consumption (VO2peak), ventilatory anaerobic threshold (VAT) and 6-minute walk distance.

Determine whether treatment with aliskiren (300 mg) compared to placebo will improve left ventricular diastolic function assessed via tissue Doppler imaging (early diastolic mitral annular velocity)

Evaluate the safety and tolerability of aliskiren in older patients with HFNEF

Detailed description: Heart Failure with Normal Ejection Fraction (HFNEF) is the most common form of heart failure, particularly in older persons. However, the optimal therapy for this disorder has not been defined. The primary chronic symptom in HFNEF is exercise intolerance, manifested by shortness of breath and fatigue with exercise. This is the major determinant of quality of life, can be measured objectively and reproducibly and is modifiable.

Minimum age: 55 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Male or female ≥ 55 years of age

- Symptomatic HFNEF of at least 1 month duration.

- Reduced early diastolic mitral annular velocity by tissue Doppler

- Left ventricular ejection fraction (LVEF ≥ 0. 50)

- Baseline exercise intolerance

- Patients who are able to provide written informed consent

- Stable medical therapy for 30 days prior to screening

Exclusion Criteria:

- Seated blood pressure ≥ 160/90 mmHg at Visit 1 (screening)

- Clinically significant pulmonary disease

- Known history of documented EF < 0. 45 at any time

- Clinically unstable heart failure, medication changes for worsening heart failure

symptoms within the past 4 weeks

- Severe anemia (Hgb <10 mg/dL)

- Clinical evidence of uncontrolled hypo or hyperthyroidism

- Clinically significant valvular heart disease

- Surgical correction of valvular heart disease within the last year

- Known familial hypertrophic cardiomyopathy or hypertrophic obstructive cardiomyopathy

- Known restrictive cardiomyopathy or systemic illness known to be associated with

infiltrative myocardial disease (e. g. amyloidosis, sarcoidosis, hemachromatosis)

- Pericardial restriction or hemodynamically significant pericardial effusion

- Cor pulmonal or other causes of right heart failure not related to LV dysfunction

- Extreme obesity (weight > 325 pounds)

- Acute coronary syndrome within past 3 months

- Coronary artery revascularization within past 3 months

- Peripheral artery revascularization within past 3 months

- Acute cerebrovascular syndrome (stroke or TIA) within the past 3 months

- Uncontrolled symptomatic brady- or tachyarrhythmia

- Creatinine > 2. 5 mg/dl at screening

- Potassium > 5. 2 meq/l at screening

- Prior treatment with, hypersensitivity to, intolerance of or contra-indication to

aliskiren

- Current treatment with antidepressant medication in the MAO inhibitor or SSRI class

- Current participation in another clinical trial

- Current treatment with both an ACE inhibitor and an angiotensin receptor antagonist.

- Known significant bilateral renal artery stenosis

- Serious non-cardiovascular disease severely limiting life expectancy

- Previous major organ (e. g., lung, liver, heart, kidney) transplantation or on a

transplant waiting list

- Any condition that is likely to prevent the patient from complying with the

requirements of the study or completing the study (e. g., history of poor compliance, alcohol or drug dependency, psychiatric illness, no permanent home)

- Pregnant women, nursing women, and women of childbearing potential.

Dalane W Kitzman, MD, Phone: 336-716-3274, Ext: 6-3274, Email: dkitzman@wfubmc.edu

Wake Forest University Health Sciences, Winston Salem, North Carolina 27157, United States; Recruiting
Dalane w Kitzman, MD, Phone: 336-716-3274, Ext: 6-3274, Email: dkitzman@wfubmc.edu
Kathy P Stewart, RT,RDCS, Phone: 336-716-6339, Ext: 6-6339, Email: kstewart@wfubmc.edu
Dalane W Kitzman, MD, Principal Investigator

Starting date: July 2009
Last updated: April 29, 2010