Anemia in Heart Failure With a Preserved Ejection Fraction (HFPEF) - Full Text View

Sponsor:	Columbia University
Collaborator:	National Institute on Aging (NIA)
Information provided by:	Columbia University
ClinicalTrials.gov Identifier:	NCT00286182

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	Phase II

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Outcomes Assessor), Placebo Control, Parallel Assignment, Safety/Efficacy Study
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:

MedlinePlus related topics: Anemia Exercise and Physical Fitness Heart Failure

Drug Information available for: Erythropoietin Epoetin alfa

U.S. FDA Resources

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 Study Completion Date:	September 2011
Estimated Primary Completion Date:	April 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
A: Experimental Erythropoietin alpha	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. Drug: Erythropoietin alpha Erythropoietin alpha is being administered weekly by subcutaneous injection using a pre-specified dosing algorithm. The dosing algorithm was 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 monitored every week to avoid rapid increases in hemoglobin/hematocrit and/or increasing blood pressure control. Dose adjustments are made to ensure that hemoglobin does not rise too rapidly (greater than 0.3 g/dL) in any given weekly interval.
B: Placebo Comparator Placebo	Drug: Erythropoietin alpha Erythropoietin alpha is being administered weekly by subcutaneous injection using a pre-specified dosing algorithm. The dosing algorithm was 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 monitored every week to avoid rapid increases in hemoglobin/hematocrit and/or increasing blood pressure control. Dose adjustments are made to ensure that hemoglobin does not rise too rapidly (greater than 0.3 g/dL) in any given weekly interval.

Arms

Assigned Interventions

A: Experimental

Erythropoietin alpha

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.

Drug: Erythropoietin alpha

Erythropoietin alpha is being administered weekly by subcutaneous injection using a pre-specified dosing algorithm. The dosing algorithm was 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 monitored every week to avoid rapid increases in hemoglobin/hematocrit and/or increasing blood pressure control. Dose adjustments are made to ensure that hemoglobin does not rise too rapidly (greater than 0.3 g/dL) in any given weekly interval.

B: Placebo Comparator

Placebo

Drug: Erythropoietin alpha

Erythropoietin alpha is being administered weekly by subcutaneous injection using a pre-specified dosing algorithm. The dosing algorithm was 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 monitored every week to avoid rapid increases in hemoglobin/hematocrit and/or increasing blood pressure control. Dose adjustments are made to ensure that hemoglobin does not rise too rapidly (greater than 0.3 g/dL) in any given weekly interval.

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:	60 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Heart failure and a preserved ejection fraction (HFPEF) - EF >=40%
Anemia - defined as hemoglobin < 12 g/dL
Age >= 60 years
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:

Presence of uncontrolled hypertension (SBP > 160 mm Hg and/or DBP > 90 mm Hg)
Resting heart rate > 120 bpm
Baseline 6-minute walk test > 450 m
Valvular heart disease (e.g. more than mild regurgitant or stenotic mitral, aortic, tricuspid, or pulmonic valve disease).
Infiltrative cardiac disease such as hemochromatosis and amyloidosis
Hypertrophic cardiomyopathy
Chronic pulmonary disease (FEV 1 < 60% predicted)
Renal failure (GFR < 15 ml/min)
Hemoglobin < 9 g/dL
BMI > 40
Exercise limited by angina, claudication, orthopedic, or neurological diseases.
Severe liver dysfunction that is defined by an international normalized ratio > 2.0, not caused by an anticoagulant.
Current or recent treatment (within past 6 months) with erythropoietin
Erythropoietin level > 100 mU/ml
Recent cardiac surgery (< 3 months)
Known iron deficiency anemia from chronic GI blood loss, uterine bleeding, or other chronic bleeding
Planned surgery during the course of the study
Significant alcohol use or illicit drug use.
Patients with a known hypercoagulable state.
Active hematologic disease (e.g. sickle cell anemia, thalassemia, chronic myelogenous leukemia) or malignancy
Patients with current seizure disorder or activity
Patients who are known to be pregnant
History of deep venous thrombosis (DVT) or pulmonary embolus (PE) within 12 months before study entry. Prior superficial thrombophlebitis is not an exclusion criterion.
History of cerebrovascular accident (CVA) within 6 months
History of transient ischemic attack (TIA) within 6 months
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).
Allergy or sensitivity to human serum albumin
Known hypersensitivity to mammalian cell-derived products

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00286182

Contacts

Contact: Mathew S Maurer, MD

212-932-4537

msm10@columbia.edu

Locations

United States, New York
Clinical Cardiovascular Research Laboratory for the Elderly	Recruiting
New York, New York, United States, 10034
Contact: Mathew S Maurer, MD 212-932-4274 msm10@columbia.edu
Principal Investigator: Mathew S Maurer, MD

Sponsors and Collaborators

Columbia University

National Institute on Aging (NIA)

Investigators

Principal Investigator:

Mathew S Maurer, MD

Columbia University

More Information

Publications:

Maurer MS, King DL, El-Khoury Rumbarger L, Packer M, Burkhoff D. Left heart failure with a normal ejection fraction: identification of different pathophysiologic mechanisms. J Card Fail. 2005 Apr;11(3):177-87.

Brucks S, Little WC, Chao T, Rideman RL, Upadhya B, Wesley-Farrington D, Sane DC. Relation of anemia to diastolic heart failure and the effect on outcome. Am J Cardiol. 2004 Apr 15;93(8):1055-7.

Silverberg DS, Wexler D, Blum M, Tchebiner J, Sheps D, Keren G, Schwartz D, Baruch R, Yachnin T, Shaked M, Zubkov A, Steinbruch S, Iaina A. The correction of anemia in severe resistant heart failure with erythropoietin and intravenous iron prevents the progression of both the heart and the renal failure and markedly reduces hospitalization. Clin Nephrol. 2002 Jul;58 Suppl 1:S37-45.

Silverberg DS, Wexler D, Sheps D, Blum M, Keren G, Baruch R, Schwartz D, Yachnin T, Steinbruch S, Shapira I, Laniado S, Iaina A. The effect of correction of mild anemia in severe, resistant congestive heart failure using subcutaneous erythropoietin and intravenous iron: a randomized controlled study. J Am Coll Cardiol. 2001 Jun 1;37(7):1775-80.

Mancini DM, Katz SD, Lang CC, LaManca J, Hudaihed A, Androne AS. Effect of erythropoietin on exercise capacity in patients with moderate to severe chronic heart failure. Circulation. 2003 Jan 21;107(2):294-9.

Klapholz M, Maurer M, Lowe AM, Messineo F, Meisner JS, Mitchell J, Kalman J, Phillips RA, Steingart R, Brown EJ Jr, Berkowitz R, Moskowitz R, Soni A, Mancini D, Bijou R, Sehhat K, Varshneya N, Kukin M, Katz SD, Sleeper LA, Le Jemtel TH; New York Heart Failure Consortium. Hospitalization for heart failure in the presence of a normal left ventricular ejection fraction: results of the New York Heart Failure Registry. J Am Coll Cardiol. 2004 Apr 21;43(8):1432-8.

Responsible Party:	Columbia University ( Mathew Maurer )
Study ID Numbers:	R01 AG027518-01, IRB-AAAB3037
Study First Received:	February 1, 2006
Last Updated:	May 23, 2008
ClinicalTrials.gov Identifier:	NCT00286182 History of Changes
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:

Epoetin Alfa
Heart Failure
Heart Diseases
Hematinics
Hematologic Diseases

Therapeutic Uses
Hematologic Agents
Anemia
Cardiovascular Diseases
Pharmacologic Actions

ClinicalTrials.gov processed this record on November 27, 2009