Clinical trial NCT00982033: Effects of Aliskiren on Patient With Heart Failure and a Normal Ejection Fraction
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Heart Failure
Keywords: Heart failure with normal ejection fraction
Elderly
Lead sponsor: Wake Forest University Health Sciences
Sponsor class: OTHER
Collaborators: name: Novartis Pharmaceuticals
First posted: 2009-09-22
Enrollment: 52
Sex: ALL
Minimum age (years): 55
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility 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(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.

Primary outcomes:
measure: Exercise Treadmill Time
timeFrame: Baseline, 24 week visit
Secondary outcomes:
Other outcomes:
Locations:
city: Winston-Salem
country: United States
facility: Wake Forest University Health Sciences
state: North Carolina
Study officials:
affiliation: Wake Forest University Health Sciences
name: Dalane W Kitzman, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Scott JM, Haykowsky MJ, Eggebeen J, Morgan TM, Brubaker PH, Kitzman DW. Reliability of peak exercise testing in patients with heart failure with preserved ejection fraction. Am J Cardiol. 2012 Dec 15;110(12):1809-13. doi: 10.1016/j.amjcard.2012.08.015. Epub 2012 Sep 13.
citation: Upadhya B, Brubaker PH, Morgan TM, Eggebeen JD, Jao GT, Stewart KP, Kitzman DW. The effect of Aliskiren on exercise capacity in older patients with heart failure and preserved ejection fraction: A randomized, placebo-controlled, double-blind trial. Am Heart J. 2018 Jul;201:164-167. doi: 10.1016/j.ahj.2018.03.019. Epub 2018 Apr 4.