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

Study Overview
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Brief Summary
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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).

Detailed Description
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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.

Official Title
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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

Conditions
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Heart Failure

Intervention / Treatment
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* Drug: aliskiren
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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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(Monoamine Oxidase) inhibitor or SSRI(Selective serotonin reuptake inhibitors) class Current participation in another clinical trial Current treatment with both an ACE(Angiotensin-converting enzyme) 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.

Ages Eligible for Study
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Minimum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Aliskiren<br>50 % of subjects participating in this trial will be on the active medication, Aliskiren 300mg qd, the other 50% will be on placebo. | Drug: aliskiren<br>* aliskiren 300mg qd versus placebo for 24 weeks.<br>* Other names: Tekturna;|
| Placebo Comparator: Placebo<br>50% of subjects will be randomized to placebo. | Drug: placebo<br>* placebo qd for 24 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Exercise Treadmill Time | Treadmill exercise time to exhaustion on the modified naughton protocol. LS-mean is in effect, within-group means appropriately adjusted for the other effects in the model. | Baseline, 24 week visit | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Heart failure with normal ejection fraction, Elderly