TCD With Transfusions Changing to Hydroxyurea

TCD 输血改为羟基脲

• 批准号: 7920182
• 负责人: Russell E Ware
• 金额: $ 417.74万
• 依托单位: ST. JUDE CHILDREN'S RESEARCH HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-21 至 2011-03-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7920182
• 关键词: Address; Adult; Adverse effects; Adverse event; Allergic Reaction; Alternative Therapies; Anemia; Antibody Formation; Arrhythmia; Autoantibodies; Blood Transfusion; Brain; Cerebrovascular Disorders; Cerebrum; Cessation of life; Chelation Therapy; Child; Chronic; Cirrhosis; Clinical; Coupled; Data; Deferoxamine; Deferoxamine Methanesulfonate; Diabetes Mellitus; Erythrocyte Transfusion; Erythrocytes; Event; Excision; Failure; Frequencies; Goals; Growth and Development function; Height; Hepatic; Hospitalization; Hypotension; Incidence; Infection; Infectious Agent; Inferior; Internal carotid artery structure; Iron; Iron Overload; Isoantibodies; Laboratories; Lead; Liver; Liver Fibrosis; Magnetic Resonance Imaging; Maintenance; Measurement; Morbidity - disease rate; Motor; Myelosuppression; Neurocognitive Deficit; Neurologic; Organ; Pain; Patients; Phase; Priapism; Primary Prevention; Prophylactic treatment; Quality of life; Randomized Clinical Trials; Reaction; Risk; Safety; Screening procedure; Sickle Cell; Sickle Cell Anemia; Source; Staging; Stroke; Stroke prevention; Sudden Death; Syncope; Time; Toxic effect; Transfusion; Venous blood sampling; Weight; acute chest syndrome; chelation; clinical efficacy; functional status; high risk; hydroxyurea; iron chelation therapy; middle cerebral artery; mortality; neuropsychological; non-compliance; ototoxicity; prevent; treatment duration; vaso-occlusive pain

DESCRIPTION (provided by applicant): Stroke occurs in 5-10% of children with SCA, and is a devastating clinical event that results in severe motor and neurocognitive deficits. To help prevent an initial (primary) stroke, young patients with SCA can receive periodic TCD screening to identify children with elevated arterial velocities in the cerebral vasculature, which portends increased primary stroke risk. For children with time-averaged maximum velocities (TAMV) in the middle cerebral artery (MCA) or internal carotid artery (ICA) elevated to the "abnormal" range (=200cm/sec), chronic erythrocyte transfusions significantly lower the risk of primary stroke. In this setting, transfusions can prevent first stroke but have serious side-effects limiting their long-term utility. Transfusions transmit infectious agents, lead to erythrocyte alloantibody or autoantibody formation, and result in iron overload. Transfusion acquired iron overload is recognized as a source of morbidity and mortality for young patients with SCA receiving transfusions for prevention of primary stroke. Chelation therapy can help prevent iron accumulation, but is difficult to tolerate and non-compliance is common. An alternative to transfusion prophylaxis for primary stroke prevention is clearly needed, especially one that also provides an opportunity to address the issue of transfusion acquired iron overload. We propose a Phase III randomized clinical trial for children with sickle cell anemia (SCA) and abnormal Transcranial Doppler (TCD) velocities, termed the "TCD With Transfusions Changing to Hydroxyurea" (TWiTCH) trial. Our hypothesis is that hydroxyurea can maintain a similar TCD velocity as erythrocyte transfusions, and therefore serve as non-inferior therapy, for primary stroke prevention in high risk children with SCA. The primary aim of the TWiTCH trial is to compare standard therapy (transfusions) to alternative therapy (hydroxyurea) for maintenance of TCD velocities in children with SCA on chronic transfusions for abnormal TCD velocities. Additional aims of TWiTCH include comparison of standard to alternative therapy for incidence of primary stroke, determination of the frequency of non-stroke neurological events and other sickle cell-related events, management of iron overload, assessment of growth and development, recording of adverse events, and measurement of quality of life. (End of Abstract)

描述（由申请人提供）： 中风发生在5-10％的SCA儿童中，这是一个毁灭性的临床事件，导致严重的运动和神经认知缺陷。为了防止初始中风（初级）中风，患有SCA的年轻患者可以进行周期性的TCD筛查，以识别大脑脉管系统中动脉速度升高的儿童，这预测了一级中风风险的增加。对于具有时间平衡的最大速度（TAMV）的儿童，大脑中动脉（MCA）或颈内动脉（ICA）（ICA）升高到“异常”范围（= 200cm/sec），慢性红细胞输血显着降低了原发性中风的风险。在这种情况下，输血可以防止首次中风，但具有严重的副作用，限制了它们的长期效用。输血传播传染剂，导致红细胞同抗体或自身抗体形成，并导致铁超载。输血获得的铁超负荷被认为是SCA接受输血以预防原发性中风的年轻患者的发病率和死亡率的来源。螯合疗法可以帮助防止铁的积累，但很难忍受，不合规是常见的。显然需要预防预防输血的一种预防输血的替代方法，尤其是那些也提供了解决输血获得的铁超载问题的机会。我们提出了针对镰状细胞贫血（SCA）和异常经颅多普勒（TCD）速度的III期随机临床试验，称为“ TCD，输血变为羟基脲”（Twitch）试验。我们的假设是，羟基脲可以保持与红细胞输血相似的TCD速度，因此可以作为非内部治疗，用于预防SCA的高风险儿童的一级中风。 Twitch试验的主要目的是将标准疗法（输血）与SCA儿童的TCD速度维持的替代疗法（羟基脲）进行比较，以在慢性输血中用于异常TCD速度。抽搐的其他目的包括将标准与原发性中风发生率的替代疗法进行比较，确定非中风神经事件的频率和其他与镰状细胞相关的事件的频率，铁超负荷的管理，生长和发育的评估，不良事件的记录以及测量生活质量。 （抽象的结尾）