Los efectos de la terapia con hierro intravenoso en dosis bajas versus dosis altas con derisomaltosa férrica en pacientes con insuficiencia cardíaca crónica y deficiencia de hierro (IRONDOSE)
Los efectos de la terapia con hierro intravenoso en dosis bajas versus dosis altas con derisomaltosa férrica en pacientes con insuficiencia cardíaca crónica y deficiencia de hierro: un ensayo aleatorizado, abierto y ciego con criterios de valoración (IRONDOSE)
This study will address whether intravenous (IV) iron repletion with a more intensive target will provide greater benefits in improving exercise capacity for patients with chronic heart failure and iron deficiency. One group of participants will receive a high-dose IV iron regimen with a more intensive target, and the other group will receive a low-dose IV iron regimen with a less intensive target.
Descripción general del estudio
Estado
Condiciones
Intervención / Tratamiento
Descripción detallada
Iron deficiency is a common and important comorbidity in heart failure. Randomized controlled trials have consistently demonstrated a beneficial effect of IV iron on exercise capacity and quality of life in iron-deficient patients with HF and reduced ejection fraction. However, these randomized controlled trials exhibit striking heterogeneity in targeting levels for maintenance strategies of IV iron repletion. Some studies (FERRIC-HF, FAIR-HF) withheld intravenous iron in cases of ferritin >800 ng/mL, hemoglobin >16.0 g/dL, or transferrin saturation (TSAT) >50%, while other studies (HEART-FID, IRONMAN) focused on targeting levels that are simply above the definition of iron deficiency. Additionally, the PIVOTAL trial showed that high-dose IV iron decreased recurrent heart failure events in patients undergoing hemodialysis compared to a lower-dose regimen. Whether functional outcomes differ between those on lower versus higher iron repletion targets among patients with heart failure remains unknown. This study will help us address this question.
This is an investigator-initiated, prospective, randomized, open-label blind endpoint study to assess the effects of high-dose IV iron repletion compared to a low-dose IV iron repletion on 12-month change in peak oxygen uptake (VO2) for patients with chronic heart failure and concomitant iron deficiency.
Patients with chronic heart failure and iron deficiency will be enrolled and randomized in a 1:1 ratio to receive a high-dose IV iron regimen and a low-dose IV iron regimen. After the initial iron repletion, ferritin concentration and TSAT were measured every three months and the results used to determine the dose of ferric derisomaltose during the follow-up period. In the high dose group, iron dosing will repeat as long as the serum ferritin was not >700ng/mL, or if TSAT was not >40%. Patients in the low dose group will receive repeat iron dosing if ferritin <100 ng/mL, or if ferritin 100-300 ng/mL and TSAT <20%, in line with criteria for iron deficiency in current guidelines.
Tipo de estudio
Inscripción (Estimado)
Fase
- Fase 4
Contactos y Ubicaciones
Estudio Contacto
- Nombre: Jingyi Ren
- Número de teléfono: 18600195099
- Correo electrónico: renjingyi1213@hotmail.com
Copia de seguridad de contactos de estudio
- Nombre: Lina Su
- Número de teléfono: 18801230212
- Correo electrónico: sln920722@163.com
Ubicaciones de estudio
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Beijing Municipality
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Beijing, Beijing Municipality, Porcelana, 100044
- Reclutamiento
- China-Japan Friendship Hospital
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Investigador principal:
- Jingyi Ren
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Contacto:
- Lina Su
- Número de teléfono: 18801230212
- Correo electrónico: sln920722@163.com
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Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Descripción
Inclusion Criteria:
- Age >18 years.
- Left ventricular ejection fraction (LVEF) <50% within 2 years prior to planned randomization (assessed by echocardiography or MRI).
- New York Heart Association (NYHA) class II ~ III.
- Either hospitalization for HF within 6 months prior to planned randomization or elevated plasma levels of natriuretic peptides within 3 months of randomization. a. For patients in sinus rhythm: NT- proBNP >300 pg/mL or BNP >100 pg/mL. b. For patients in atrial fibrillation: NT-proBNP >600 pg/mL or BNP >200 pg/mL.
- Subjects with stable CHF (NYHA II/III functional class) on optimal background therapy (as determined by the investigator) for at least 4 weeks with no dose changes of heart failure drugs during the last 2 weeks (with the exception of diuretics).
- Serum ferritin <100 ng/mL or serum ferritin 100-300 ng/mL and TSAT <20%.
- Able and willing to perform a CPET at the time of randomization.
- Able and willing to provide informed consent.
Exclusion Criteria:
- Hemoglobin <9.0 g/dL or Hemoglobin >15.0 g/dL.
- Renal dialysis or MDRD/CKD-EPI estimated glomerular filtration rate (eGFR) <15 ml/min/1.73m2.
- Body weight <35 kg.
- Heart failure was secondary to valvular diseases or congenital heart diseases.
- History of acquired iron overload; known hemochromatosis or first relatives with hemochromatosis.
- Known hypersensitivity to ferric derisomaltose or other IV iron product.
- Known active infection (defined as currently treated with oral or intravenous antibiotics), bleeding (gastrointestinal hemorrhagia, menorrhagia, history of peptic ulcer with no evidence of healing or inflammatory bowel disease), malignancy, and hemolytic anemia.
- History of chronic liver disease and/or alanine transaminase (ALT) or aspartate transaminase (AST) >3 times the upper limit of the normal range; myelodysplastic disorder; and known HIV/AIDS disease.
- Acute myocardial infarction, acute coronary syndrome, transient ischemic attack, or stroke within 3 months prior to randomization.
- Revascularization therapy (coronary artery bypass grafting, percutaneous intervention, or major surgery) within 3 months prior to randomization; or planning cardiac surgery or revascularization.
- Already receiving erythropoietin, IV or oral iron therapy, and blood transfusion in previous 30 days prior to randomization.
- Use of concurrent immunosuppressive therapy
- Any of the following diseases that hinders exercise testing: severe musculoskeletal disease, unstable angina, obstructive cardiomyopathy, severe uncorrected valvular disease, or uncontrolled slow or rapid arrhythmia (mean ventricular rate >100 beats/min at rest), or uncontrolled hypertension with blood pressure >160/100 mm Hg.
- Investigator considers a possible alternative diagnosis to account for the patient's HF symptoms: severe obesity, primary pulmonary hypertension, or chronic obstructive pulmonary disease.
- Pregnancy or breast feeding.
- Participation in another intervention study involving a drug or device within the past 90 days.
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: Aleatorizado
- Modelo Intervencionista: Asignación paralela
- Enmascaramiento: Único
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
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Experimental: High dose
Participants randomized to this arm will receive repeat iron dosing as long as the serum ferritin was not >700 ng/mL, or if TSAT was not >40% during follow-up. Iron to be administered as ferric derisomaltose. Ferric derisomaltose will be administered according to the dosing schedule determined by the patient's body weight and hemoglobin value. Infused over a minimum of 15 mins for doses up to and including 1000mg, and a minimum of 30 mins for doses >1000mg. |
After baseline assessment, participants will be randomized in a 1:1 ratio to receive a high-dose IV iron regimen and a low-dose IV iron regimen. After the initial iron repletion, ferritin concentration and TSAT were measured every three months and the results used to determine the dose of ferric derisomaltose during follow-up. In the high-dose group, participants will receive repeat iron dosing as long as the serum ferritin was not >700 ng/mL, or if TSAT was not >40% during follow-up.
Otros nombres:
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Comparador activo: Low dose
Participants randomized to this arm will receive repeat iron dosing if ferritin <100 ng/mL or if ferritin 100-300 ng/mL and TSAT <20% during follow-up. Iron to be administered as ferric derisomaltose in analogy to high-dose arm. |
In the low-dose group, participants will receive repeat iron dosing if ferritin <100 ng/mL or if ferritin 100-300 ng/mL and TSAT >20% during follow-up.
Otros nombres:
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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 peak VO2 (ml/min/kg）
Periodo de tiempo: Baseline to Week 52
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Peak VO2 measured by a maximal effort Cardiopulmonary Exercise Test (CPET) |
Baseline to Week 52
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Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Cambio en la distancia a pie de 6 minutos (m)
Periodo de tiempo: Línea de base hasta la semana 26 y la semana 52
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Línea de base hasta la semana 26 y la semana 52
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Change in VO2 at ventilatory threshold (ml/min）
Periodo de tiempo: Baseline to Week 52
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Measured by CPET |
Baseline to Week 52
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Change in heart rate at peak exercise (bpm)
Periodo de tiempo: Baseline to Week 52
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Measured by CPET |
Baseline to Week 52
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Change in peak respiratory exchange ratio
Periodo de tiempo: Baseline to Week 52
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Measured by CPET |
Baseline to Week 52
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Change in myocardial iron content by cardiac magnetic resonance imaging T2 star
Periodo de tiempo: Baseline to Week 52
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Measured by cardiac magnetic resonance imaging |
Baseline to Week 52
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Change in skeletal muscle iron content by magnetic resonance imaging T2 star
Periodo de tiempo: Baseline to Week 52
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Measured by skeletal muscle magnetic resonance imaging |
Baseline to Week 52
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Change in the clinical summary score by Kansas City Cardiomyopathy Questionnaire (KCCQ)
Periodo de tiempo: Baseline to Week 52
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The KCCQ is a validated instrument for self-assessment of quality of life and health status in heart failure patients. The clinical summary score, which is derived from the physical limitations and heart failure symptoms domains of the KCCQ is a valid measure for assessing the patient's health aspects that may be influenced by CV medications. Scores are transformed to a range of 0-100, in which higher scores reflect better health status. |
Baseline to Week 52
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Change in the EQ-5D-5L questionnaire indexed value
Periodo de tiempo: Baseline to Week 52
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EQ-5D-5L: European Quality of Life-5 Dimensions-5 Levels The EQ 5D questionnaire consists of a health descriptive system for participants to self-classify and rate their health status on the day of administration. The descriptive system includes 5 items/dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression, which are coded from 1 (best state) to 5 (worst state). |
Baseline to Week 52
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Change in cognitive function score by Mini-Mental State Examination (MMSE)
Periodo de tiempo: Baseline to Week 52
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The MMSE is a cognitive test. The score is ranged from 0-30 (units of a scale). 30 points is the better outcome. The investigators will assess the change in the score. |
Baseline to Week 52
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Change in concentration of N-terminal pro-brain natriuretic peptide (NT-proBNP, pg/mL)
Periodo de tiempo: Baseline to Week 52
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Tested in blood samples |
Baseline to Week 52
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Change in left ventricular ejection fraction (LVEF, %)
Periodo de tiempo: Baseline to Week 52
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Assessed by echocardiography |
Baseline to Week 52
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Change in left ventricular global longitudinal stress (LVGLS, %)
Periodo de tiempo: Baseline to Week 52
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Assessed by echocardiography |
Baseline to Week 52
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Mortality and heart failure-related hospitalization rates
Periodo de tiempo: Up to 52 weeks
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Effects on mortality and HF-related hospitalization rates in patients with heart failure. |
Up to 52 weeks
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Colaboradores e Investigadores
Patrocinador
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Actual)
Finalización primaria (Estimado)
Finalización del estudio (Estimado)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Actual)
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
Otros números de identificación del estudio
- 2023-ZF-62
Plan de datos de participantes individuales (IPD)
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Información sobre medicamentos y dispositivos, documentos del estudio
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