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

Anemia Clinical Trial

Official title:

Efficacy of Treating Anemia in Heart Failure With a Preserved Ejection Fraction (HFPEF) on Ventricular Function, Exercise Capacity and Health Status

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00286182
• Other study ID #: AAAB3037
• Secondary ID: R01AG027518-01
• Status: Completed
• Phase: Phase 2
• First received: February 1, 2006
• Last updated: February 25, 2015
• Start date: July 2007
• Est. completion date: November 2012

Study information

• Verified date: February 2015
• Source: Columbia University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 56
• Est. completion date: November 2012
• Est. primary completion date: November 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 55 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Anemia
• Heart Failure

Intervention

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.
• Placebo
Placebo

Locations

Country	Name	City	State
United States	Clinical Cardiovascular Research Laboratory for the Elderly	New York	New York

Sponsors (2)

Lead Sponsor	Collaborator
Mathew S. Maurer	National Institute on Aging (NIA)

Country where clinical trial is conducted

United States, 

References & Publications (6)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Left ventricular end diastolic volume (by three dimensional echocardiography)		6 month	No
Secondary	Peak oxygen consumption by cardiopulmonary exercise testing		6 month	No
Secondary	6-minute walk duration		3 month and 6 month	No
Secondary	Health status (Kansas City Cardiomyopathy Questionnaire)		3 month and 6 month	No
Secondary	Left ventricular structure (volume and mass) and function (stroke volume, cardiac output) measured non-invasively		3 month and 6 month	No
Secondary	Hospitalization		6 month	Yes