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.
調査の概要
詳細な説明
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.
研究の種類
入学 (実際)
段階
- フェーズ 3
連絡先と場所
研究場所
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Cholet、フランス
- Cholet Hospital
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Tours、フランス
- UH Tours
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参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
説明
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.
研究計画
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：ランダム化
- 介入モデル：並列代入
- マスキング：トリプル
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
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実験的：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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プラセボコンパレーター：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. |
この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Recruitment rate
時間枠：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
時間枠：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
時間枠：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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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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The proportion of patients lost to follow-up at each visit
時間枠：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
時間枠：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
時間枠：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
時間枠：28 days
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Mean serum hemoglobin value
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28 days
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ICU mortality
時間枠：up to 90 days
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ICU mortality
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up to 90 days
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病院死亡率
時間枠：最長90日
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病院死亡率
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最長90日
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ICU length of stay
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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),
時間枠：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)
時間枠：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
時間枠：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
時間枠：90 days
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Thrombolic event: pulmonary embolism, venous or arterial thrombosis
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90 days
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協力者と研究者
捜査官
- スタディディレクター：Sigismond Lasocki, MD、Angers University Hospital
研究記録日
主要日程の研究
研究開始 (実際)
一次修了 (実際)
研究の完了 (予想される)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
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