Department of Clinical Pharmacology and Epidemiology, Mario Negri Sud Consortium, 66030 S, Maria Imbaro (CH), Italy.
Trials. 2010 Jun 9;11:70. doi: 10.1186/1745-6215-11-70.
Anemia is a risk factor for death, adverse cardiovascular outcomes and poor quality of life in patients with chronic kidney disease (CKD). Erythropoietin Stimulating Agents (ESA) are commonly used to increase hemoglobin levels in this population. In observational studies, higher hemoglobin levels (around 11-13 g/dL) are associated with improved survival and quality of life compared to hemoglobin levels around 9-10 g/dL. A systematic review of randomized trials found that targeting higher hemoglobin levels with ESA causes an increased risk of adverse vascular outcomes. It is possible, but has never been formally tested in a randomized trial, that ESA dose rather than targeted hemoglobin concentration itself mediates the increased risk of adverse vascular outcomes. The Clinical Evaluation of the DOSe of Erythropoietins (C.E. DOSE) trial will assess the benefits and harms of a high versus a low fixed ESA dose for the management of anemia in patients with end stage kidney disease.
METHODS/DESIGN: This is a randomized, prospective open label blinded end-point (PROBE) trial due to enrol 2204 hemodialysis patients in Italy. Patients will be randomized 1:1 to 4000 IU/week versus 18000 IU/week of intravenous epoietin alfa or beta, or any other ESA in equivalent doses. The dose will be adjusted only if hemoglobin levels fall outside the 9.5-12.5 g/dL range. The primary outcome will be a composite of all-cause mortality, non fatal stroke, non fatal myocardial infarction and hospitalization for cardiovascular causes. Quality of life and costs will also be assessed.
The C.E.DOSE study will help inform the optimal therapeutic strategy for the management of anemia of hemodialysis patients, improving clinical outcomes, quality of life and costs, by ascertaining the potential benefits and harms of different fixed ESA doses.
Clinicaltrials.gov NCT00827021.
贫血是慢性肾脏病（CKD）患者死亡、不良心血管结局和生活质量下降的一个风险因素。促红细胞生成素刺激剂（ESA）常用于提高该人群的血红蛋白水平。在观察性研究中，与血红蛋白水平在 9-10g/dL 左右相比，较高的血红蛋白水平（约 11-13g/dL）与改善的生存率和生活质量相关。一项对随机试验的系统评价发现，ESA 靶向更高的血红蛋白水平会增加不良血管结局的风险。ESA 剂量而不是目标血红蛋白浓度本身可能介导不良血管结局风险增加，这是有可能的，但从未在随机试验中得到正式检验。临床评价红细胞生成素剂量（C.E. DOSE）试验将评估高与低固定 ESA 剂量治疗终末期肾病患者贫血的获益与危害。
方法/设计：这是一项在意大利进行的、随机、前瞻性、开放标签、盲终点（PROBE）试验，共纳入 2204 名血液透析患者。患者将以 1:1 的比例随机分为每周 4000IU 与每周 18000IU 的静脉内 epoetin alfa 或 beta，或任何其他等效剂量的 ESA。仅当血红蛋白水平超出 9.5-12.5g/dL 范围时才会调整剂量。主要结局为全因死亡率、非致死性卒中、非致死性心肌梗死和心血管原因住院的复合结局。生活质量和成本也将进行评估。
C.E.DOSE 研究将通过确定不同固定 ESA 剂量的潜在获益和危害，帮助确定血液透析患者贫血管理的最佳治疗策略，改善临床结局、生活质量和成本。
Clinicaltrials.gov NCT00827021。
