Anemia in Heart Failure With a Preserved Ejection Fraction (HFPEF)

The recruitment status of this study is unknown because the information has not been verified recently.
Verified November 2011 by Columbia University.
Recruitment status was  Active, not recruiting
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Columbia University
ClinicalTrials.gov Identifier:
NCT00286182
First received: February 1, 2006
Last updated: November 28, 2011
Last verified: November 2011
  Purpose

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.


Condition Intervention Phase
Anemia
Drug: Erythropoietin alpha
Drug: Placebo
Phase 2

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by Columbia University:

Primary Outcome Measures:
  • Left ventricular end diastolic volume (by three dimensional echocardiography) [ Time Frame: 6 month ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 80
Study Start Date: July 2007
Estimated Primary Completion Date: March 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Drug: Placebo
Placebo

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   55 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Heart failure and a preserved ejection fraction (HFPEF) - EF >=40%
  2. Anemia - defined as hemoglobin < 12 g/dL
  3. Age >= 55 years
  4. Patients must be able to understand and sign the informed consent document after the nature of the study has been fully explained, prior to beginning any study procedures.

Exclusion Criteria:

  1. Presence of uncontrolled hypertension (Systolic blood pressure > 160 mm Hg and/or diastolic blood pressure > 90 mm Hg)
  2. Resting heart rate > 120 bpm
  3. Baseline 6-minute walk test > 450 meters
  4. Valvular heart disease (e.g. more than mild regurgitant or stenotic mitral, aortic, tricuspid, or pulmonic valve disease).
  5. Infiltrative cardiac disease such as hemochromatosis and amyloidosis
  6. Hypertrophic cardiomyopathy
  7. Chronic pulmonary disease (FEV 1 < 60% predicted)
  8. Renal failure (GFR < 15 ml/min)
  9. Hemoglobin < 8 g/dL
  10. BMI > 40
  11. Exercise limited by angina, claudication, orthopedic, or neurological diseases.
  12. Severe liver dysfunction that is defined by an international normalized ratio > 2.0, not caused by an anticoagulant.
  13. Current or recent treatment (within past 6 months) with erythropoietin
  14. Erythropoietin level > 100 mU/ml
  15. Recent cardiac surgery (< 3 months)
  16. Known iron deficiency anemia from chronic GI blood loss, uterine bleeding, or other chronic bleeding
  17. Planned surgery during the course of the study
  18. Significant alcohol use or illicit drug use.
  19. Patients with a known hypercoagulable state.
  20. Active hematologic disease (e.g. sickle cell anemia, thalassemia, chronic myelogenous leukemia) or malignancy
  21. Patients with current seizure disorder or activity
  22. Patients who are known to be pregnant
  23. History of deep venous thrombosis (DVT) or pulmonary embolus (PE) within 12 months before study entry. Prior superficial thrombophlebitis is not an exclusion criterion.
  24. History of cerebrovascular accident (CVA) within 6 months
  25. History of transient ischemic attack (TIA) within 6 months
  26. History of acute coronary syndrome (ACS), or other arterial thrombosis within 6 months before study entry. ACS includes unstable angina, Q wave myocardial infarction (QwMI), and non-Q wave myocardial infarction (NQMI).
  27. Allergy or sensitivity to human serum albumin
  28. Known hypersensitivity to mammalian cell-derived products
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00286182

Locations
United States, New York
Clinical Cardiovascular Research Laboratory for the Elderly
New York, New York, United States, 10034
Sponsors and Collaborators
Columbia University
Investigators
Principal Investigator: Mathew S Maurer, MD Columbia University
  More Information

Publications:

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Columbia University
ClinicalTrials.gov Identifier: NCT00286182     History of Changes
Other Study ID Numbers: AAAB3037, R01AG027518-01
Study First Received: February 1, 2006
Last Updated: November 28, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by Columbia University:
Heart Failure
Elderly
Diastolic Dysfunction
Anemia
Ventricular End Diastolic Volume
Aged

Additional relevant MeSH terms:
Anemia
Heart Failure
Hematologic Diseases
Heart Diseases
Cardiovascular Diseases
Epoetin alfa
Hematinics
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 19, 2014