Anemia in Heart Failure With a Preserved Ejection Fraction (HFPEF)
30. januar 2017 opdateret af: Mathew S. Maurer
Efficacy of Treating Anemia in Heart Failure With a Preserved Ejection Fraction (HFPEF) on Ventricular Function, Exercise Capacity and Health Status
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.
Studieoversigt
Status
Afsluttet
Betingelser
Intervention / Behandling
Detaljeret beskrivelse
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.
Undersøgelsestype
Interventionel
Tilmelding (Faktiske)
56
Fase
- Fase 2
Kontakter og lokationer
Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.
Studiesteder
-
-
New York
-
New York, New York, Forenede Stater, 10034
- Clinical Cardiovascular Research Laboratory for the Elderly
-
-
Deltagelseskriterier
Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.
Berettigelseskriterier
Aldre berettiget til at studere
51 år og ældre (Voksen, Ældre voksen)
Tager imod sunde frivillige
Ingen
Køn, der er berettiget til at studere
Alle
Beskrivelse
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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)
- 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
Studieplan
Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Behandling
- Tildeling: Randomiseret
- Interventionel model: Parallel tildeling
- Maskning: Dobbelt
Våben og indgreb
Deltagergruppe / Arm |
Intervention / Behandling |
|---|---|
|
Eksperimentel: 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.
|
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.
Andre navne:
|
|
Placebo komparator: Placebo
Placebo consists of saline injections.
|
Placebo
|
Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
|
Change in Left Ventricular End-diastolic Volume
Tidsramme: Baseline and 6 month
|
This outcome measure is collected using a three dimensional echocardiography.
|
Baseline and 6 month
|
Samarbejdspartnere og efterforskere
Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.
Sponsor
Samarbejdspartnere
Efterforskere
- Ledende efterforsker: Mathew S Maurer, MD, Columbia University
Publikationer og nyttige links
Den person, der er ansvarlig for at indtaste oplysninger om undersøgelsen, leverer frivilligt disse publikationer. Disse kan handle om alt relateret til undersøgelsen.
Generelle publikationer
- 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.
- 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.
- 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. doi: 10.1016/s0735-1097(01)01248-7.
- 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.
- 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.
- 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.
- 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.
- 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.
Datoer for undersøgelser
Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.
Studer store datoer
Studiestart
1. juli 2007
Primær færdiggørelse (Faktiske)
1. november 2012
Studieafslutning (Faktiske)
1. november 2012
Datoer for studieregistrering
Først indsendt
1. februar 2006
Først indsendt, der opfyldte QC-kriterier
1. februar 2006
Først opslået (Skøn)
3. februar 2006
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Faktiske)
10. marts 2017
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
30. januar 2017
Sidst verificeret
1. januar 2017
Mere information
Begreber relateret til denne undersøgelse
Yderligere relevante MeSH-vilkår
Andre undersøgelses-id-numre
- AAAB3037
- R01AG027518-01 (U.S. NIH-bevilling/kontrakt)
Plan for individuelle deltagerdata (IPD)
Planlægger du at dele individuelle deltagerdata (IPD)?
Uafklaret
Disse oplysninger blev hentet direkte fra webstedet clinicaltrials.gov uden ændringer. Hvis du har nogen anmodninger om at ændre, fjerne eller opdatere dine undersøgelsesoplysninger, bedes du kontakte register@clinicaltrials.gov. Så snart en ændring er implementeret på clinicaltrials.gov, vil denne også blive opdateret automatisk på vores hjemmeside .