Erythropoietin to Improve Critical Care Patient Outcomes (EPO-ICU-FS)
Erythropoietin to Improve Critical Care Patient Outcomes: Feasibility Study of a Multicenter, Randomized, Placebo-controlled Trial of Subcutaneous Erythropoietin Injection for Intensive Care Patients
Recently, the french societies for critical care (SFAR and SRLF) produced guidelines for anemia treatment in critically ill patients that recommend the use of erythropoietin (EPO) in these patients, but the european society (ESICM) recommended against the use of EPO in this patients, despite recent meta analysis showing a lower mortality in patients treated with EPO.
Nevertheless, RCT on EPO in the ICU are quite all, new data are thus needed. Before conducting a large study on EPO in anemic patients in the ICU, we propose to cinduct a feasability RCT to evaluate the feasability of such a study.
Descripción general del estudio
Estado
Condiciones
Intervención / Tratamiento
Descripción detallada
Anemia is very common in intensive care patients, affecting approximately two-thirds of patients on admission, with a mean admission hemoglobin (Hb) level of 11.0 g/dl. The severity of anemia is associated with increased morbidity and mortality. Its pathophysiology is complex, involving blood loss (from repeated blood sampling, invasive procedures, surgical interventions, etc.) and inflammation. The latter is responsible for a decrease in endogenous erythropoietin (EPO) production and a decreased bone marrow response, which can be very prolonged (half of the patients discharged from ICU with anemia are still anemic at 6 months of discharge, with low levels of EPO, compared to the observed Hb levels). On this basis, several randomized clinical trials (RCTs) evaluating the effect of EPO on the transfusion rate in this population were performed in the 1990s-2000s. The authors showed a modest reduction in blood transfusion, which was not considered clinically relevant in view of the cost of EPO at that time.
Since then, meta-analyses evaluating the benefits and risks of EPO in intensive care patients suggest a positive impact of EPO on mortality. The largest, including 34 studies (and 930,470 patients) reports a reduction in the relative risk of mortality of 0.76, 95% CI [0.61 - 0.92]. Beyond the reduction in red blood cell transfusions, the benefit of EPO could be directly due to its erythropoietic effect (correction of anemia) and/or its anti-inflammatory/anti-apoptotic properties. Based on this literature, the French critical care societies have recently recommended the use of EPO. However, the European Society of Intensive Care Medicine (ESICM) recently recommended against the use of EPO, based on the same literature, but suggested that the benefit of EPO should be evaluated. Indeed, the main obstacle to recommending the use of EPO seems to be economic, whereas the arrival on the market of biosimilar molecules has significantly reduced these costs.
Most of the trials on EPO in critical care patients (and included in the meta-analyses) are quite old (about 15 years) and none of them had mortality as primary endpoint. In addition, transfusion practices and the quality of blood products have changed significantly over the years. In this context of disagreement on the recommendations for the use of EPO in these patients, but of potential benefit on mortality, there is an urgent need to evaluate whether EPO decreases mortality in adult anemic patients admitted to intensive care. However, calculation of the number of patients needed to evaluate the benefit of EPO on mortality in this population yields a number of patients to be included of the order of 1800-2000 patients.
Before considering the implementation of a multicenter study involving such a large number of patients, a pilot study evaluating the feasibility and inclusion capacity for such a study seems indispensable according to the latest CONSORT recommendations.
Tipo de estudio
Inscripción (Actual)
Fase
- Fase 3
Contactos y Ubicaciones
Ubicaciones de estudio
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Cholet, Francia
- Cholet Hospital
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Tours, Francia
- UH Tours
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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:
- Adult patients (age > 18 years),
- admitted to intensive care for more than 72 hours and less than 7 days
- who have received invasive ventilatory support and/or treatment with a vasoactive agent for at least one day since admission
- with an Hb level < 12 g/dl,
- with consent from the patient or patient's relative (or emergency inclusion procedure).
Exclusion Criteria:
- Moribund patient,
- Current hospitalization for acute coronary syndrome,
- Recent history of thromboembolic event (< 3 months),
- Uncontrolled hypertension despite adequate antihypertensive therapy,
- Myelodysplasia or chronic pathology requiring iterative transfusions,
- EPO treatment within the last 30 days,
- Participation in another interventional trial of an erythropoiesis-stimulating agent or anemia treatment,
- Expected discharge from the intensive care unit within 24 hours,
- Known hypersensitivity to EPO or any of its components,
- A history of erythroblastopenia following erythropoietin therapy
- Pregnant, breast-feeding or parturient woman
- Person deprived of liberty by judicial or administrative decision
- Person under forced psychiatric care
- Person under a legal protection measure.
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: Aleatorizado
- Modelo Intervencionista: Asignación paralela
- Enmascaramiento: Triple
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
|---|---|
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Experimental: erythropoietin
Erythropoietin alpha or theta 40,000 UI (1 ml) sc each week if Hb <12 g/dL (for maximum 5 weeks)
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Patients receive a subcutaneous injection of 40,000 IU of erythropoietin alfa or zêta, repeated weekly until Day 28 (if the hemoglobin level is <12 g/dl and the patient remains hospitalized). The study treatments are administered by an open-label nurse. In both groups, before each injection, iron deficiency (defined as reticulocyte Hb <29 pg, or hepcidin <41 µg/L, or ferritin <100 µg/L, or ferritin <300 µg/L with transferrin saturation <20%) is treated with intravenous iron infusion (depending on the product available at the center). A restrictive transfusion strategy is recommended as long as the patient remains in the ICU, according to recent recommendations. Six visits are scheduled: V1 for inclusion and the first injection, V2 at Day 7(±2 days) for the second injection, V3 at Day 14(±2 days) for the third injection, V4 at Day 21(±2 days) for the fourth injection, V5 at Day 28(±2 days) for the fifth injection. |
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Comparador de placebos: Placebo
saline sc injection (1 ml) each weeks if Hb <12 g/dL, for a maximum of 5 weeks,
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In the control arm, patients receive a subcutaneous injection of placebo (0.9% NaCl) according to the same schedule. The study treatments are administered by an open-label nurse. In both groups, before each injection, iron deficiency (defined as reticulocyte Hb <29 pg, or hepcidin <41 µg/L, or ferritin <100 µg/L, or ferritin <300 µg/L with transferrin saturation <20%) is treated with intravenous iron infusion (depending on the product available at the center). A restrictive transfusion strategy is recommended as long as the patient remains in the ICU, according to recent recommendations. Six visits are scheduled: V1 for inclusion and the first injection, V2 at Day 7(±2 days) for the second injection, V3 at Day 14(±2 days) for the third injection, V4 at Day 21(±2 days) for the fourth injection, V5 at Day 28(±2 days) for the fifth injection. |
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Recruitment rate
Periodo de tiempo: 90 days
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≥50% of eligible patients will need to be enrolled, but the trial will not be feasible if the inclusion rate is ≤ 25% or less
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90 days
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Adherence to allocation groups
Periodo de tiempo: 90 days
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A high level of matching of randomization and group allocation should be achieved, with at least 85% of included patients receiving protocol-allocated treatment, but if ≤ 65% patients receive protocol-allocated treatment, the trial is not feasible
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90 days
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Completion of follow-up of included patients
Periodo de tiempo: 90 days
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≥ 85% of patients should be followed through to the end of follow-up, but if <65% patients are followed through to the last visit, the protocol will not be feasible
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90 days
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Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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The proportion of patients lost to follow-up at each visit
Periodo de tiempo: 7, 14, 21, 28 and 90 days
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The proportion of patients lost to follow-up at each visit
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7, 14, 21, 28 and 90 days
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The rate of missing data for mortality outcome
Periodo de tiempo: 90 days
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The rate of missing data for mortality outcome
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90 days
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The rate of compliance with the therapeutic protocol at each visit for inpatients
Periodo de tiempo: 7, 14, 21, and 28 days
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The rate of compliance with the therapeutic protocol at each visit for inpatients
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7, 14, 21, and 28 days
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Mean serum hemoglobin value
Periodo de tiempo: 28 days
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Mean serum hemoglobin value
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28 days
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ICU mortality
Periodo de tiempo: up to 90 days
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ICU mortality
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up to 90 days
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Mortalidad hospitalaria
Periodo de tiempo: hasta 90 días
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Mortalidad hospitalaria
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hasta 90 días
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ICU length of stay
Periodo de tiempo: up to 90 days
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ICU length of stay
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up to 90 days
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Hospital length of stay
Periodo de tiempo: up to 90 days
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Hospital length of stay
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up to 90 days
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Blood transfusion
Periodo de tiempo: 90 days
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Proportion of patients who received at least one red blood cell transfusion
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90 days
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number of red blood cells transfused
Periodo de tiempo: 90 days
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number of red blood cells transfused
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90 days
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90 days survival analysis
Periodo de tiempo: 90 days
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90 days survival analysis
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90 days
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Occurrence of hospital readmission (censored at 90 days after inclusion),
Periodo de tiempo: 90 days
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at least one hospital readmission after the hospital discharge
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90 days
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Number of days living at home (or previous place of living)
Periodo de tiempo: 90 days
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Number of days living at home (or previous place of living) at D90
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90 days
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Quality of life measured by the EQ-5D 5L scale, EuroQol 5 dimensions
Periodo de tiempo: 90 days
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The value from this scale records the patient's self-rated health on a vertical visual analogue scale, where the endpoints are labelled 'The best health you can imagine'.
The scale is rated from 0 to 100.
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90 days
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Proportion of patients with a thromboembolic event
Periodo de tiempo: 90 days
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Thrombolic event: pulmonary embolism, venous or arterial thrombosis
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90 days
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Colaboradores e Investigadores
Patrocinador
Investigadores
- Director de estudio: Sigismond Lasocki, MD, Angers University hospital
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Actual)
Finalización primaria (Actual)
Finalización del estudio (Anticipado)
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
- EPO-ICU-FS
Plan de datos de participantes individuales (IPD)
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Descripción del plan IPD
Información sobre medicamentos y dispositivos, documentos del estudio
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