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- Ensayo clínico NCT00286182
Anemia in Heart Failure With a Preserved Ejection Fraction (HFPEF)
30 de enero de 2017 actualizado por: 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.
Descripción general del estudio
Estado
Terminado
Condiciones
Intervención / Tratamiento
Descripción detallada
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.
Tipo de estudio
Intervencionista
Inscripción (Actual)
56
Fase
- Fase 2
Contactos y Ubicaciones
Esta sección proporciona los datos de contacto de quienes realizan el estudio e información sobre dónde se lleva a cabo este estudio.
Ubicaciones de estudio
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New York
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New York, New York, Estados Unidos, 10034
- Clinical Cardiovascular Research Laboratory for the Elderly
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Criterios de participación
Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.
Criterio de elegibilidad
Edades elegibles para estudiar
53 años y mayores (Adulto, Adulto Mayor)
Acepta Voluntarios Saludables
No
Géneros elegibles para el estudio
Todos
Descripción
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
Plan de estudios
Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: Aleatorizado
- Modelo Intervencionista: Asignación paralela
- Enmascaramiento: Doble
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
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Experimental: 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.
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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.
Otros nombres:
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Comparador de placebos: Placebo
Placebo consists of saline injections.
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Placebo
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¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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Change in Left Ventricular End-diastolic Volume
Periodo de tiempo: Baseline and 6 month
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This outcome measure is collected using a three dimensional echocardiography.
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Baseline and 6 month
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Colaboradores e Investigadores
Aquí es donde encontrará personas y organizaciones involucradas en este estudio.
Patrocinador
Colaboradores
Investigadores
- Investigador principal: Mathew S Maurer, MD, Columbia University
Publicaciones y enlaces útiles
La persona responsable de ingresar información sobre el estudio proporciona voluntariamente estas publicaciones. Estos pueden ser sobre cualquier cosa relacionada con el estudio.
Publicaciones Generales
- 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.
Fechas de registro del estudio
Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.
Fechas importantes del estudio
Inicio del estudio
1 de julio de 2007
Finalización primaria (Actual)
1 de noviembre de 2012
Finalización del estudio (Actual)
1 de noviembre de 2012
Fechas de registro del estudio
Enviado por primera vez
1 de febrero de 2006
Primero enviado que cumplió con los criterios de control de calidad
1 de febrero de 2006
Publicado por primera vez (Estimar)
3 de febrero de 2006
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
10 de marzo de 2017
Última actualización enviada que cumplió con los criterios de control de calidad
30 de enero de 2017
Última verificación
1 de enero de 2017
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
Otros números de identificación del estudio
- AAAB3037
- R01AG027518-01 (Subvención/contrato del NIH de EE. UU.)
Plan de datos de participantes individuales (IPD)
¿Planea compartir datos de participantes individuales (IPD)?
Indeciso
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