Stroke Prevention in Nigeria: SPRING 2

尼日利亚的中风预防：春季 2

基本信息

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
项目类别：
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

项目摘要

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 型混合试验来评估羟基脲的有效性对生活在尼日利亚的镰状细胞性贫血（SCA）儿童进行初级中风预防的治疗。我们的团队只是完成了一项双盲、平行组 III 期随机对照试验 (SPRING)，我们比较了低剂量至中剂量羟基脲用于 SCA 和异常儿童的初级卒中预防经颅多普勒 (TCD) 速度（>200 厘米/秒）。 TCD 速度异常的儿童中风率较高每 100 人年发生约 10.7 起事件的风险（STOP 试验中的观察组）。在低水平（n=109）羟基脲组和中等剂量（n=111）羟基脲组的中风发病率分别为每 100 人 1.2 例和 1.9 例。年，p=0.77（综合发病率为每 100 人年 1.5）。尽管功效相同与低剂量羟基脲相比，两个治疗组的中风预防效果更好有效预防严重急性疼痛和全因住院。我们的研究结果支持了美国血液学会关于羟基脲治疗初级卒中预防的循证指南低收入环境。我们的假设待检验：在一项多中心单臂 I 型混合试验中，针对患有以下疾病的儿童：羟基脲治疗TCD速度异常，中风发生率将不劣于SPRING 试验结果，非劣效上限为每 100 人年 4 次中风。点估计法用于根据尼日利亚儿科医生对什么的判断来确定非劣效性界值最大中风率对于证明治疗的有效性和合理性具有临床意义中风高危人群。总体样本量为 220 名参与者的非劣效性测试将达到 91% 当预期中风比例为 0.035 时，以 0.050 显着性水平检测非劣效性的功效最短随访期为 2.5 年，每年随访损失率为 10%。参与者将被跟踪为根据标准护理，包括每 3 个月就诊一次和每 6 个月进行一次全血细胞计数。我们将实现以下目标：1) 确定异常儿童中首次卒中和 TIA 的发生率 1型混合试验中用羟基脲处理2.5年的TCD速度； 2）评估实施情况以及扩展 RE-AIM 框架内干预措施的可持续性； 3）评估成本效益低剂量与高剂量羟基脲用于 TCD 异常儿童初级卒中预防的比较速度。三名尼日利亚多重首席研究员、统计学家和护士的能力建设将重点关注三个领域 - a) 开发尼日利亚数据协调中心和所需技能支持临床试验； b) 为护士开发区域 TCD 课程，加强任务转移和覆盖范围，以及 c) 对比较低剂量和中等剂量羟基脲的 I 型混合试验进行成本效益分析。