EXpanding Treatment for Existing Neurological Disease (EXTEND): An Open-Label Phase II Clinical Trial of Hydroxyurea Treatment in Sickle Cell Anemia.
EXpanding Treatment for Existing Neurological Disease (EXTEND): An Open-Label Phase II Clinical Trial of Hydroxyurea Treatment in Sickle Cell Anemia.
复制标题
扩大现有神经疾病（扩展）的治疗方法：镰状细胞贫血中羟基脲治疗的开放标签II期临床试验。
DOI：
10.2196/resprot.5872
复制
发表时间：
2016-09-12
影响因子：
1.7
通讯作者：
Ware RE
中科院分区：
文献类型：
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作者：
Rankine-Mullings AE;Little CR;Reid ME;Soares DP;Taylor-Bryan C;Knight-Madden JM;Stuber SE;Badaloo AV;Aldred K;Wisdom-Phipps ME;Latham T;Ware RE
镰状细胞性贫血（SCA）的脑血管病变始于儿童时期，以颅内动脉狭窄为特征，具有缺血性卒中的高风险。通过经颅多普勒（TCD）筛查和长期输血治疗可以降低中风风险;然而，这种方法在许多发展中国家是不切实际的。越来越多的证据支持使用羟基脲预防和治疗SCA儿童脑血管疾病。最近，我们报道，羟基脲显着减少转换条件TCD速度异常速度，是否可以使用羟基脲的新诊断的严重脑血管疾病的儿童开始输血治疗的地方仍然未知。现有神经系统疾病扩展治疗（EXTEND）试验的主要目的是研究开放标签的羟基脲治疗18个月后与治疗前值相比对最大时均平均血流速度（TAMV）的影响。次要目的包括羟基脲对系列TCD速度的影响、神经和非神经事件的发生率、生活质量（QOL）、身体成分和代谢、毒性和治疗反应、脑磁共振成像（MRI）和磁共振血管造影（MRA）的变化、疾病严重程度的遗传和血清学标志物以及认知和肺功能。这项前瞻性II期试验将在牙买加招募年龄在2 - 17岁之间的SCA儿童，这些儿童具有条件性（170-199 cm/sec）或异常（≥ 200 cm/sec）TCD速度。每日口服羟基脲，并递增至最大耐受剂量（MTD）。受试者将在牙买加金斯顿的镰状细胞单位（SCU）接受每月一次的观察，直至达到MTD，然后每3个月一次。TCD将每6个月进行一次。目前，在预计的50名参与者中，已有43名参与者登记。有一个退出由于移民，没有永久筛选失败。在入组的43例受试者中，37例受试者已开始研究治疗。本试验研究了在输血治疗前条件性或TCD速度异常的儿童中，以MTD水平进行羟基脲治疗的效果，这可能代表了在SCA儿童中建立适当的非输血方案预防卒中的重要进展。试验结果将对疾病负担最高的发展中国家具有深远意义。ClinicalTrials.gov NCT 02556099; https://clinicaltrials.gov/ct2/show/NCT02556099（由WebCite存档，网址为http：//www.webcitation.org/6k1yMAa9G）
Cerebral vasculopathy in sickle cell anemia (SCA) begins in childhood and features intracranial arterial stenosis with high risk of ischemic stroke. Stroke risk can be reduced by transcranial doppler (TCD) screening and chronic transfusion therapy; however, this approach is impractical in many developing countries. Accumulating evidence supports the use of hydroxyurea for the prevention and treatment of cerebrovascular disease in children with SCA. Recently we reported that hydroxyurea significantly reduced the conversion from conditional TCD velocities to abnormal velocities; whether hydroxyurea can be used for children with newly diagnosed severe cerebrovascular disease in place of starting transfusion therapy remains unknown. The primary objective of the EXpanding Treatment for Existing Neurological Disease (EXTEND) trial is to investigate the effect of open label hydroxyurea on the maximum time-averaged mean velocity (TAMV) after 18 months of treatment compared to the pre-treatment value. Secondary objectives include the effects of hydroxyurea on serial TCD velocities, the incidence of neurological and non-neurological events, quality of life (QOL), body composition and metabolism, toxicity and treatment response, changes to brain magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA), genetic and serologic markers of disease severity, and cognitive and pulmonary function. This prospective Phase II trial will enroll children with SCA in Jamaica, between the ages of 2 and 17 years, with either conditional (170-199 cm/sec) or abnormal (≥ 200 cm/sec) TCD velocities. Oral hydroxyurea will be administered daily and escalated to the maximum tolerated dose (MTD). Participants will be seen in the Sickle Cell Unit (SCU) in Kingston, Jamaica monthly until achieving MTD, and then every 3 months. TCD will be performed every 6 months. Currently, 43 participants have been enrolled out of a projected 50. There was one withdrawal due to immigration, with no permanent screen failures. Of the 43 enrolled, 37 participants have initiated study treatment. This trial investigates the effects of hydroxyurea treatment at MTD in children with conditional or abnormal TCD velocities before transfusion therapy and may represent an important advance towards establishing a suitable non-transfusion protocol for stroke prevention in children with SCA. The trial outcomes will have profound significance in developing countries where the disease burden is highest. ClinicalTrials.gov NCT02556099; https://clinicaltrials.gov/ct2/show/NCT02556099 (Archived by WebCite at http://www.webcitation.org/6k1yMAa9G)