TCD with Transfusions Changing to Hydroxyurea - SDMC

TCD 输血改为羟基脲 - SDMC

• 批准号: 8598924
• 负责人: BARRY R DAVIS
• 金额: $ 67.42万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
• 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 2015-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8598924
• 关键词: Academic Medical Centers; Address; Adult; Adverse effects; Adverse event; Alternative Therapies; Annual Reports; Archives; Arrhythmia; Autoantibodies; Blood Transfusion; Case Report Form; Cerebrovascular Circulation; Cerebrovascular Disorders; Chelation Therapy; Child; Chronic; Clinical; Clinical Investigator; Clinical Research; Clinical Trials; Collaborations; Communication; Communities; Companions; Computers; Coupled; Data; Data Coordinating Center; Data Set; Databases; Deferoxamine; Deferoxamine Methanesulfonate; Diabetes Mellitus; Doppler Ultrasound; Effectiveness; Electronics; Enrollment; Ensure; Erythrocyte Transfusion; Erythrocytes; Evaluation; Event; Excision; Frequencies; Funding; Goals; Grant; Growth and Development function; Incidence; Infectious Agent; Internal carotid artery structure; Iron; Iron Chelation; Iron Overload; Isoantibodies; Laboratories; Lead; Leadership; Literature; Liver Cirrhosis; Liver Fibrosis; Maintenance; Manuals; Masks; Measurement; Measures; Medical; Methods; Monitor; Morbidity - disease rate; National Heart, Lung, and Blood Institute; Neurocognitive Deficit; Neurologic; Organ; Pain; Paper; Patients; Phase; Play; Preparation; Primary Prevention; Process; Prophylactic treatment; Protocols documentation; Publications; Quality of life; Randomized; Randomized Clinical Trials; Reporting; Research Institute; Research Personnel; Risk; Risk Factors; Role; Safety; Saint Jude Children' s Research Hospital; Sample Size; Secure; Serious Adverse Event; Services; Sickle Cell; Sickle Cell Anemia; Site; Site Visit; Source; South Carolina; Specimen; Statistical Methods; Stroke; Stroke prevention; Sudden Death; System; Testing; Time; Training; Transfusion; Venous blood sampling; abstracting; acute chest syndrome; arm; base; clinical efficacy; clinical research site; data management; design; electronic data; experience; high risk; hydroxyurea; improved; intracranial artery; iron chelation therapy; meetings; middle cerebral artery; mortality; motor deficit; non-compliance; operation; patient registry; prevent; protocol development; rho; screening; software systems; statistics; success; web site

Project Summary/Abstract 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 (e200cm/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.

项目总结/文摘

项目成果

Hydroxycarbamide versus chronic transfusion for maintenance of transcranial doppler flow velocities in children with sickle cell anaemia-TCD With Transfusions Changing to Hydroxyurea (TWiTCH): a multicentre, open-label, phase 3, non-inferiority trial.

• DOI: 10.1016/s0140-6736(15)01041-7
• 发表时间: 2016-02-13
• 期刊: Lancet (London, England)
• 作者: Ware RE;Davis BR;Schultz WH;Brown RC;Aygun B;Sarnaik S;Odame I;Fuh B;George A;Owen W;Luchtman-Jones L;Rogers ZR;Hilliard L;Gauger C;Piccone C;Lee MT;Kwiatkowski JL;Jackson S;Miller ST;Roberts C;Heeney MM;Kalfa TA;Nelson S;Imran H;Nottage K;Alvarez O;Rhodes M;Thompson AA;Rothman JA;Helton KJ;Roberts D;Coleman J;Bonner MJ;Kutlar A;Patel N;Wood J;Piller L;Wei P;Luden J;Mortier NA;Stuber SE;Luban NLC;Cohen AR;Pressel S;Adams RJ
• 通讯作者: Adams RJ

Liver iron concentration measurements by MRI in chronically transfused children with sickle cell anemia: baseline results from the TWiTCH trial.

• DOI: 10.1002/ajh.24089
• 发表时间: 2015-09
• 期刊: American journal of hematology
• 影响因子: 12.8
• 作者: Wood JC;Pressel S;Rogers ZR;Odame I;Kwiatkowski JL;Lee MT;Owen WC;Cohen AR;St Pierre T;Heeney MM;Schultz WH;Davis BR;Ware RE;TWiTCH Investigators
• 通讯作者: TWiTCH Investigators