Heart Failure
Conditions
Keywords
Heart failure with normal ejection fraction, Elderly
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.
Interventions
DRUGaliskiren
aliskiren 300mg qd versus placebo for 24 weeks.
DRUGplacebo
placebo qd for 24 weeks
Sponsors
Novartis Pharmaceuticals
Wake Forest University Health Sciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
55 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Exercise Treadmill Time | Baseline, 24 week visit | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Aliskiren 50 % of subjects participating in this trial will be on the active medication, Aliskiren 300mg qd.
aliskiren: aliskiren 300mg qd for 24 weeks. | 25 |
| Placebo 50% of subjects participating in this trial will be randomized to placebo.
placebo: placebo qd for 24 weeks. | 27 |
| Total | 52 |
Baseline characteristics
| Characteristic | Aliskiren | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 69.3 years STANDARD_DEVIATION 6.3 | 70.6 years STANDARD_DEVIATION 7.7 | 69.9 years STANDARD_DEVIATION 7.04 |
| Sex: Female, Male Female | 19 Participants | 23 Participants | 42 Participants |
| Sex: Female, Male Male | 6 Participants | 4 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 6 / 25 | 13 / 27 |
| serious Total, serious adverse events | 0 / 25 | 4 / 27 |
Outcome results
Primary
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.
Time frame: Baseline, 24 week visit
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Aliskiren | Exercise Treadmill Time | Baseline | 621 seconds | Standard Deviation 120 |
| Aliskiren | Exercise Treadmill Time | 24 Week | 624 seconds | Standard Deviation 151 |
| Aliskiren | Exercise Treadmill Time | LS Mean | 607 seconds | Standard Deviation 13 |
| Placebo | Exercise Treadmill Time | 24 Week | 579 seconds | Standard Deviation 145 |
| Placebo | Exercise Treadmill Time | Baseline | 580 seconds | Standard Deviation 126 |
| Placebo | Exercise Treadmill Time | LS Mean | 605 seconds | Standard Deviation 12 |
p-value: 0.9ANCOVA