Stroke Prevention in Nigeria: SPRING 2

尼日利亚的中风预防：春季 2

• 批准号: 10741173
• 负责人: SHEHU UMAR ABDULLAHI
• 金额: $ 61.76万
• 依托单位: VANDERBILT UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2028-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10741173
• 关键词: Acute Pain; Adoption; American Society of Hematology; Anemia; Area; Assessment tool; Blood Cell Count; Blood Flow Velocity; Brain; Cephalic; Child; Childhood; Clinic Visits; Clinical; Clinical Trials; Cost Effectiveness Analysis; Data Coordinating Center; Dimensions; Dose; Double-Blind Method; Effectiveness; Event; Fogarty International Center; Funding; Goals; Guidelines; Hospitalization; Incidence; Intervention; Judgment; Literature; Low income; Maintenance; Measures; Methods; National Institute of Neurological Disorders and Stroke; Neurology; Nigeria; Nigerian; Nurses; Outpatients; Pain; Participant; Persons; Phase; Physicians; Population; Prevention program; Principal Investigator; Publishing; Quality-Adjusted Life Years; Randomized, Controlled Trials; Reach, Effectiveness, Adoption, Implementation, and Maintenance; Recommendation; Relative Risks; Research; Risk Reduction; Sample Size; Sickle Cell Anemia; Stroke; Stroke prevention; Testing; Time; Visit; arm; cost; cost effectiveness; cost-effectiveness evaluation; cost-effectiveness ratio; effectiveness evaluation; effectiveness testing; evidence based guidelines; follow-up; health care model; health care service utilization; high risk; hybrid type 1 trial; hydroxyurea; implementation evaluation; incremental cost-effectiveness; member; multidisciplinary; neuroimaging; open label; pediatrician; phase III trial; phase IV trial; prevent; preventive intervention; primary outcome; relative cost; routine care; screening; secondary outcome; sickling; skills; standard care; stroke incidence; stroke risk; treatment group; trial comparing; Acute Pain; Adoption; American Society of Hematology; Anemia; Area; Assessment tool; Blood Cell Count; Blood Flow Velocity; Brain; Cephalic; Child; Childhood; Clinic Visits; Clinical; Clinical Trials; Cost Effectiveness Analysis; Data Coordinating Center; Dimensions; Dose; Double-Blind Method; Effectiveness; Event; Fogarty International Center; Funding; Goals; Guidelines; Hospitalization; Incidence; Intervention; Judgment; Literature; Low income; Maintenance; Measures; Methods; National Institute of Neurological Disorders and Stroke; Neurology; Nigeria; Nigerian; Nurses; Outpatients; Pain; Participant; Persons; Phase; Physicians; Population; Prevention program; Principal Investigator; Publishing; Quality-Adjusted Life Years; Randomized, Controlled Trials; Reach, Effectiveness, Adoption, Implementation, and Maintenance; Recommendation; Relative Risks; Research; Risk Reduction; Sample Size; Sickle Cell Anemia; Stroke; Stroke prevention; Testing; Time; Visit; arm; cost; cost effectiveness; cost-effectiveness evaluation; cost-effectiveness ratio; effectiveness evaluation; effectiveness testing; evidence based guidelines; follow-up; health care model; health care service utilization; high risk; hybrid type 1 trial; hydroxyurea; implementation evaluation; incremental cost-effectiveness; member; multidisciplinary; neuroimaging; open label; pediatrician; phase III trial; phase IV trial; prevent; preventive intervention; primary outcome; relative cost; routine care; screening; secondary outcome; sickling; skills; standard care; stroke incidence; stroke risk; treatment group; trial comparing

SUMMARY: We propose a multicenter open-label, single-arm type I hybrid trial to assess the effectiveness of hydroxyurea therapy for primary stroke prevention in children with sickle cell anemia (SCA) living in Nigeria. Our team just completed a double-blind, parallel-group phase III randomized controlled trial (SPRING), where we compared low-dose to moderate-dose hydroxyurea for primary stroke prevention in children with SCA and abnormal transcranial Doppler (TCD) velocities (>200 cm/sec). Children with abnormal TCD velocities have a high stroke risk of approximately 10.7 events per 100 person-years (observation arm in the STOP trial). In the low- (n=109) and moderate-dose (n=111) hydroxyurea groups, the stroke incidence rates were 1.2 and 1.9 per 100 person- years, respectively, p=0.77 (combined incidence rate 1.5 per 100 person-year). Despite equal efficacy for stroke prevention in both treatment groups, moderate- when compared to low-dose hydroxyurea, was more effective in preventing severe acute pain and all-cause hospitalizations. Our findings supported the American Society of Hematology's evidence-based guidelines for hydroxyurea therapy for primary stroke prevention in low-income settings. Our hypothesis to be tested: in a multicenter single-arm type I hybrid trial, for children with abnormal TCD velocities treated with hydroxyurea, the stroke incidence rate will be non-inferior to the SPRING trial results, with an upper non-inferiority margin of 4 strokes per 100-person-years. The point estimate method was used to determine the non-inferiority margin based on the Nigerian pediatrician's judgment of what maximum stroke rate would be clinically meaningful to demonstrate the effectiveness and justify treatment for the high-risk stroke group. A non-inferiority test with an overall sample size of 220 participants will achieve 91% power at a 0.050 significance level to detect non-inferiority when the expected proportion of strokes is 0.035, a minimum follow-up period of 2.5 years and a loss to follow-up of 10% per year. Participants will be followed as per standard care, including clinic visits every 3 months and complete blood cell counts every 6 months. We will conduct the following aims:1) Determine the incidence of the first stroke and TIA in children with abnormal TCD velocities treated with hydroxyurea for 2.5 years in the type 1 hybrid trial; 2) Evaluate the implementation and sustainability of the intervention within the extended RE-AIM framework; 3) Evaluate the cost-effectiveness of low- compared to a higher dose of hydroxyurea for primary stroke prevention in children with abnormal TCD velocities. Capacity building for the three Nigerian Multiple Principal Investigators, the statisticians, and nurses will be focused on three areas- a) developing a Nigerian data coordinating center and the required skills to support a clinical trial; b) developing a regional TCD course for nurses, enhancing task shifting and reach, and c) performing cost-effective analysis for the type I hybrid trial comparing low-and moderate dose hydroxyurea.

概括： 我们提出了一项多中心开放标签，单臂I型混合试验，以评估羟基脲的有效性 住在尼日利亚的镰状细胞贫血（SCA）儿童预防原发性中风的治疗。我们的团队只是 完成了双盲，平行组III期随机对照试验（春季），我们在其中比较 SCA和异常儿童的低剂量至中剂量羟基脲用于预防原发性中风 经颅多普勒（TCD）速度（> 200 cm/sec）。异常TCD速度的儿童中风很高 每100人年大约10.7个事件的风险（在停止审判中观察部门）。在低 - （n = 109）中 和中剂量（n = 111）羟基脲组，中风的发病率为1.2和1.9每100人 - 年分别为p = 0.77（每100人年1.5的组合发病率）。尽管有同等效力 与低剂量羟基脲相比，这两个治疗组的中风预防中等 有效预防严重的急性疼痛和全因住院治疗。我们的发现支持美国人 血液学学会基于证据的羟基脲治疗指南，用于预防初级中风 低收入设置。我们要检验的假设：在多中心单臂I型混合动力试验中 用羟基脲处理的异常TCD速度，中风发生率将不属于春季 试验结果，高劣质边际每100人年为4笔。点估计方法 被用来根据尼日利亚儿科医生对什么的判断来确定非效率保证金 最高中风率在临床上有意义，以证明有效性并证明治疗的理由 高风险中风组。总体样本量为220名参与者的非效率测试将达到91％ 当预期的中风比例为0.035时，在0.050的显着性水平上以0.050的显着性水平，A 最低随访期为2。5年，每年损失10％。参与者将被遵循 根据标准护理，包括每3个月诊所就诊，每6个月完成一次血细胞计数。我们 将执行以下目的：1）确定异常儿童的第一笔中风和TIA的发生率 在1型混合试验中，用羟基脲处理的TCD速度已有2。5年； 2）评估实施 以及在扩展的Re-Aim框架内的干预措施的可持续性； 3）评估成本效益 与异常TCD儿童的原发性预防剂量的羟基脲相比，低剂量的低剂量 速度。尼日利亚三位多重研究人员，统计学家和护士的能力建设 将集中于三个领域：a）开发尼日利亚数据协调中心以及所需的技能 支持临床试验； b）为护士开发区域性TCD课程，增强任务的转移和触及范围，以及 c）对比较低剂量羟基脲的I型混合动力试验进行具有成本效益的分析。