Anemia in Heart Failure With a Preserved Ejection Fraction (HFPEF)
The purpose of this study is to determine if treating anemia with subcutaneous erythropoetin in patients with heart failure and a preserved ejection fraction (HFPEF) will be associated with reverse ventricular remodeling, significant improvements in exercise capacity, and improved health status, as compared with placebo.
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||Efficacy of Treating Anemia in Heart Failure With a Preserved Ejection Fraction (HFPEF) on Ventricular Function, Exercise Capacity and Health Status|
- Left ventricular end diastolic volume (by three dimensional echocardiography) [ Time Frame: 6 month ] [ Designated as safety issue: No ]
- Peak oxygen consumption by cardiopulmonary exercise testing [ Time Frame: 6 month ] [ Designated as safety issue: No ]
- 6-minute walk duration [ Time Frame: 3 month and 6 month ] [ Designated as safety issue: No ]
- Health status (Kansas City Cardiomyopathy Questionnaire) [ Time Frame: 3 month and 6 month ] [ Designated as safety issue: No ]
- Left ventricular structure (volume and mass) and function (stroke volume, cardiac output) measured non-invasively [ Time Frame: 3 month and 6 month ] [ Designated as safety issue: No ]
- Hospitalization [ Time Frame: 6 month ] [ Designated as safety issue: Yes ]
|Study Start Date:||July 2007|
|Estimated Primary Completion Date:||March 2012 (Final data collection date for primary outcome measure)|
Experimental: Erythropoietin alpha
Subcutaneous erythropoietin will be administered once weekly to achieve a target hemoglobin of 13 g/dL. Subjects will be dosed with the study drug for 24 weeks. The administration of study drug will be performed according to a pre-specified treatment algorithm that adjust erythropoietin dosages based on the rate of rise of the hemoglobin.
Drug: Erythropoietin alpha
Erythropoietin alpha is administered weekly by subcutaneous injection using a pre-specified dosing algorithm. The dosing algorithm is designed to make adjustments based on the rate of rise (ROR) of the hemoglobin over a one week period, as well as the absolute hemoglobin value. Subjects initially received active treatment with 7,500 units of erythropoietin given weekly by subcutaneously injection. Subjects are carefully monitored (e.g. every week) to avoid rapid increases in hemoglobin/hematocrit and/or increasing blood pressure control. Dose adjustments are made if the hemoglobin rises too rapidly (greater than 0.3 g/dL) in any given weekly interval.
Other Name: Erythropoietin alpha (Epogen)
Placebo Comparator: Placebo
Placebo consists of saline injections.
Heart failure frequently occurs in patients with a preserved ejection fraction (HFPEF) and affected subjects are predominantly elderly women with several co-morbid conditions. Despite the diversity of underlying clinical pathologies and co-morbid conditions present in these patients, a common pathophysiologic explanation is generally applied to explain their clinical symptoms. Our preliminary data show that a significant subgroup with HFPEF has increases in ventricular volumes and expanded plasma volumes, consistent with a volume overloaded state. In the setting of a preserved EF with end diastolic volume increased, stroke volume must increase, indicating a high output state. Anemia may be an important, modifiable contributor to the observed high output and volume overload as well as exercise intolerance in elderly HFPEF patients, abnormal ventricular remodeling and impaired overall health status and quality of life. This protocol evaluates the impact of treating anemia in subjects with HFPEF. The specific aims of the current study are to provide a comprehensive and mechanistically based assessment of how correcting anemia in subjects with HFPEF can impact on functional capacity, ventricular structure and function and overall health status. We propose to perform a randomized, prospective, double blind study in 80 subjects with HFPEF to test the hypothesis that the administration of subcutaneous erythropoietin will be associated with reverse ventricular remodeling, significant improvements in exercise capacity and improved health status.
|United States, New York|
|Clinical Cardiovascular Research Laboratory for the Elderly|
|New York, New York, United States, 10034|
|Principal Investigator:||Mathew S Maurer, MD||Columbia University|