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

NCT00286182 | Completed Phase 2 Results DMC

• 2 other identifiers: AAAB3037R01AG027518-01
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Anemia

Keywords

Heart Failure; Elderly; Diastolic Dysfunction; Anemia; Ventricular End Diastolic Volume; Aged

Outcome Measures

Primary Outcomes (1)

• Change in Left Ventricular End-diastolic Volume

  This outcome measure is collected using a three dimensional echocardiography.

  Baseline and 6 month

Study Arms (2)

Erythropoietin alpha

EXPERIMENTAL

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

Placebo

PLACEBO COMPARATOR

Placebo consists of saline injections.

Drug: Placebo

Interventions

Erythropoietin alpha DRUG

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.

Also known as: Erythropoietin alpha (Epogen)

Erythropoietin alpha

Placebo DRUG

Placebo

Placebo

Eligibility Criteria

• Age: 55 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Heart failure and a preserved ejection fraction (HFPEF) - EF \>=40%
• Anemia - defined as hemoglobin \< 12 g/dL
• Age \>= 55 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.

You may not qualify if:

• Presence of uncontrolled hypertension (Systolic blood pressure \> 160 mm Hg and/or diastolic blood pressure \> 90 mm Hg)
• Resting heart rate \> 120 bpm
• Baseline 6-minute walk test \> 450 meters
• 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 \< 8 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)

Sponsors & Collaborators

• Mathew S. Maurer: lead
• National Institute on Aging (NIA): collaborator

Study Sites (1)

Clinical Cardiovascular Research Laboratory for the Elderly

New York, New York, 10034, United States

Location

Related Publications (9)

• 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. doi: 10.1016/j.cardfail.2004.10.006.

  PMID: 15812744 BACKGROUND

• 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. doi: 10.1016/j.amjcard.2003.12.062.

  PMID: 15081458 BACKGROUND

• 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.

  PMID: 12227725 BACKGROUND

• 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. doi: 10.1016/s0735-1097(01)01248-7.

  PMID: 11401110 BACKGROUND

• 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. doi: 10.1161/01.cir.0000044914.42696.6a.

  PMID: 12538431 BACKGROUND

• 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. doi: 10.1016/j.jacc.2003.11.040.

  PMID: 15093880 BACKGROUND

• Green P, Babu BA, Teruya S, Helmke S, Prince M, Maurer MS. Impact of epoetin alfa on left ventricular structure, function, and pressure volume relations as assessed by cardiac magnetic resonance: the heart failure preserved ejection fraction (HFPEF) anemia trial. Congest Heart Fail. 2013 Jul-Aug;19(4):172-9. doi: 10.1111/chf.12027. Epub 2013 Mar 20.

  PMID: 23517485 DERIVED

• Maurer MS, Teruya S, Chakraborty B, Helmke S, Mancini D. Treating anemia in older adults with heart failure with a preserved ejection fraction with epoetin alfa: single-blind randomized clinical trial of safety and efficacy. Circ Heart Fail. 2013 Mar;6(2):254-63. doi: 10.1161/CIRCHEARTFAILURE.112.969717. Epub 2012 Dec 20.

  PMID: 23258574 DERIVED

• Altincatal A, Macarthur RB, Teruya S, Helmke S, Maurer MS. A dosing algorithm for erythropoietin alpha in older adults with heart failure and a preserved ejection fraction. Cardiovasc Ther. 2013 Apr;31(2):92-9. doi: 10.1111/j.1755-5922.2011.00295.x. Epub 2011 Aug 26.

  PMID: 21884028 DERIVED

MeSH Terms

Conditions

Anemia; Heart Failure

Interventions

Epoetin Alfa

Condition Hierarchy (Ancestors)

Hematologic Diseases; Hemic and Lymphatic Diseases; Heart Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Erythropoietin; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Results Point of Contact

• Title: Mathew Maurer, MD, Professor of Medicine at the Columbia University Medical Center
• Organization: Columbia University

msm10@cumc.columbia.edu

212-305-9808

Study Officials

• Mathew S Maurer, MD

  Columbia University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor of Clinical Medicine

Study Record Dates

• First Submitted: February 1, 2006
• First Posted: February 3, 2006
• Study Start: July 1, 2007
• Primary Completion: November 1, 2012
• Study Completion: November 1, 2012
• Last Updated: March 10, 2017
• Results First Posted: June 10, 2016

Record last verified: 2017-01

Locations

US (1)