AnemiaPhase 2NCT00286182

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

A Phase 2 study testing Erythropoietin alpha in people with Anemia, run by Mathew S. Maurer at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

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… Read more about this study

Who is it for?: Ages 55 years and older
Conditions the study is for: Anemia
What is being tested?: Erythropoietin alpha
Type of treatment: Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 56 participants
Where: 1 siteUnited States
Study dates: Jul 2007to Nov 2012
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 55 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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.

Who cannot join

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

Show all 28Show fewer

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)
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

Trial locations and contacts

1 site in 1 country.

United States1 site

Clinical Cardiovascular Research Laboratory for the Elderly
New York, New York, 10034

Other trials in United States

About this study

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

Read the 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.

Conditions: Anemia
Being tested: Erythropoietin alpha, Placebo
Keywords: Heart Failure, Elderly, Diastolic Dysfunction, Anemia, Ventricular End Diastolic Volume, Aged
Medical subject headings: Anemia, Heart Failure

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Erythropoietin alphaDrug
Also called Erythropoietin alpha (Epogen)
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.
PlaceboDrug
Placebo

Study groups in NCT00286182
Study group	Role	What they receive
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. Receives: Drug: Erythropoietin alpha
Placebo	Placebo comparator	Placebo consists of saline injections. Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

Change in Left Ventricular End-diastolic Volume
This outcome measure is collected using a three dimensional echocardiography.
Measured: Baseline and 6 month

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jul 2007Nov 2012

First posted3 Feb 2006 (estimated)
Study startJul 2007
Primary completionNov 2012
Study completionNov 2012

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (9)Papers the sponsor has linked to this study.
Other trials for AnemiaStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Who is masked: Participant, Outcomes assessor
Enrolment: 56 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00286182
Sponsor's protocol ID: AAAB3037
Other IDs: R01AG027518-01
Status last verified: Jan 2017
First submitted: 1 Feb 2006
Last updated: 10 Mar 2017
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
Individual data sharing: Undecided

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. doi: 10.1016/j.cardfail.2004.10.006.
PubMed 15812744
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.
PubMed 15081458
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.
PubMed 12227725
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.
PubMed 11401110
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.
PubMed 12538431
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.
PubMed 15093880
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.
PubMed 23517485
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.
PubMed 23258574
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.
PubMed 21884028

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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All Anemia trials

Study at a glance

From the registry record, last updated by the sponsor on 10 Mar 2017. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Efficacy of Treating Anemia in Heart Failure With a Preserved Ejection Fraction (HFPEF) on Ventricular Function, Exercise Capacity and Health Status
ClinicalTrials.gov ID: NCT00286182
Acronym / sponsor ID: AAAB3037
Conditions: Anemia
Keywords: Heart Failure, Elderly, Diastolic Dysfunction, Anemia, Ventricular End Diastolic Volume, Aged
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 56 participants (actual)
Lead sponsor: Mathew S. MaurerUniversity, hospital or other
Collaborators: National Institute on Aging (NIA)
Study start: Jul 2007
Primary completion: Nov 2012 (actual)
Study completion: Nov 2012 (actual)
First posted: 3 Feb 2006 (estimated)
Results: Posted 10 Jun 2016

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind (participant, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
Erythropoietin alpha	Experimental	Drug: Erythropoietin alphaSubcutaneous 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.
Placebo	Placebo comparator	Drug: PlaceboPlacebo consists of saline injections.

Who may qualify

Ages: 55 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (4 listed)

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.

Key exclusion criteria (28 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Erythropoietin alphaAlso: Erythropoietin alpha (Epogen)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
PlaceboPlacebo	Drug	Placebo

Primary outcome

Change in Left Ventricular End-diastolic Volume
Time frame: Baseline and 6 month
This outcome measure is collected using a three dimensional echocardiography.

Results and safety

Results posted to the registry on 10 Jun 2016, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Erythropoietin Alpha	28	23
Placebo	28	25

Primary outcome: Change in Left Ventricular End-diastolic Volume

Time frame: Baseline and 6 month. Mean (Standard Error). Unit: mL

Measure	Erythropoietin Alpha n = 23	Placebo n = 25
Value	-6 (14)	-4 (16)

Adverse events

Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Erythropoietin Alpha	19 of 28 (67.9%)	0 of 28 (0%)	Not reported
Placebo	18 of 28 (64.3%)	0 of 28 (0%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 10 Mar 2017.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 15812744Maurer 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.
Background: PubMed 15081458Brucks 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.
Background: PubMed 12227725Silverberg 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.
Background: PubMed 11401110Silverberg 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.
Background: PubMed 12538431Mancini 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.
Background: PubMed 15093880Klapholz 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.
Derived from this study: PubMed 23517485Green 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.
Derived from this study: PubMed 23258574Maurer 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.
Derived from this study: PubMed 21884028Altincatal 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.
Individual participant dataSharing planned: Undecided

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Mathew S Maurer, MD principal investigator

Columbia University

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Erythropoietin alpha in people with Anemia, run by Mathew S. Maurer at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 28 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 10 Mar 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 10 Jun 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in Left Ventricular End-diastolic Volume (time frame: Baseline and 6 month). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00286182, which also lists 9 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Mar 2017.