Multi-arm Optimization of Stroke Thrombolysis (MOST) Stroke Trial

中风溶栓 (MOST) 中风试验的多臂优化

基本信息

批准号：
9705913
负责人：
Opeolu M Adeoye
金额：
$ 580.1万
依托单位：
UNIVERSITY OF CINCINNATI
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-06-01 至 2021-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9705913
关键词：
Acute Adjuvant Analgesic Adult Aftercare Age Alteplase Antiplatelet Drugs Argatroban Arteries Blinded Clinical Clinical Trials Data Monitoring Committees Cost Measures Cost Savings Data Deterioration Disabled Persons Doctor of Philosophy Double-Blind Method Eligibility Determination Enrollment Futility Glycoproteins Grant Hemorrhage Hospitals Hour Injury Intervention Intracranial Hemorrhages Intravenous Ischemic Stroke Leadership Measures Medical National Clinical Trials Network National Institute of Neurological Disorders and Stroke Neurologic Outcome Outcome Measure Patients Pharmaceutical Preparations Phase Phase II Clinical Trials Placebos Probability Public Health Publishing Quality of life Randomized Randomized Controlled Trials Recommendation Reperfusion Therapy Reporting Research Personnel Safety Site South Carolina State Hospitals Stroke Symptoms Testing Therapy trial Thrombectomy Thrombin Time Translating U-Series Cooperative Agreements United States United States National Institutes of Health Universities active method arm base cost cost effectiveness data management disability burden eptifibatide ethnic difference functional independence gender difference improved outcome inhibitor/antagonist life time cost mortality operation phase II trial phase III trial post stroke prevent racial and ethnic recruit response safety outcomes standard care standard of care stroke patient stroke trials success three-arm trial thrombolysis treatment arm treatment effect treatment response

项目摘要

The Multi-arm Optimization of Stroke Thrombolysis (MOST) stroke trial will be a double-blinded multi-center, randomized controlled Phase 3 trial with a maximum of 1200 subjects. The trial will determine if adult (age ≥18 years) subjects with an NIH stroke scale score ≥6 at baseline treated within three hours of symptom onset with rt-PA followed by argatroban or eptifibatide are more likely to have a favorable outcome at 3 months (mRS) as compared to subjects treated with standard IV rt-PA alone. Subjects in all treatment arms may proceed to endovascular therapy (ET) as clinically warranted. The three arms of the trial include: rt-PA plus placebo, rt-PA plus argatroban, and rt-PA plus eptifibatide. Subjects are initially randomized in a 1:1:1 ratio up to 150 subjects enrolled. Response adaptive randomization would then favor the treatment arm that appears to be most favorable based on accrued data. After 500 subjects are enrolled, the treatment arm(s) that appears most favorable will be selected for fixed randomization versus standard treatment. Fixed randomization arms must be selected at 500 subjects. The trial may be stopped early for futility at 500 subjects if no intervention arm appears better than rt-PA alone (<20% predictive probability). Interim analyses will also occur at 700 and 900 subjects. At these times, the trial may be stopped for futility if no intervention arm appears better than rt-PA alone (<5% predictive probability); the trial may be stopped early for efficacy if an arm appears to be better than rt-PA (>99% predictive probability). The primary 3-month efficacy endpoint is performed by central investigators blinded to treatment assignment. Additional endpoints will include: (1) other outcome measures including NIHSS, the quality of life utility as measured via EuroQol EQ-5D at 90 days); (2) early response to treatment as determined by an NIHSSS of 0-2 at 24 hours; (3) mRS at 30 days; (4) differences in treatment effect in ET versus non-ET subjects; and, (5) racial/ethnic and gender differences in treatment effect. The trial will be supported by three NINDS cooperative agreement grants: (1) to the University of Cincinnati NINDS Stroke Trial Network (NSTN) National Clinical Coordinating Center (PI: Joseph P. Broderick, MD) to provide project and site management; (2) to the NSTN National Data Management Center (NDMC) at the Medical University of South Carolina (PI: Yuko Y. Palesch, PhD) to provide data management and statistical expertise; and (3) to the Project PI for clinical leadership, site recruitment and study conduct and operations (Multiple PIs: Opeolu Adeoye, MD; Andrew Barreto, MD; Joseph P. Broderick, MD; James Grotta, MD).

中风溶栓的多臂优化（大多数）中风试验将是双盲的多中心，随机对照3期试验最多1200名受试者。试验将确定成人是否（年龄≥18岁）年）在症状发作三小时内治疗的基线时，NIH中风量表得分≥6的受试者 RT-PA随后是Argatroban或Eptifibatide，更有可能在3个月（MRS）的有利结果为与仅用标准IV RT-PA处理的受试者相比。所有治疗臂中的受试者都可以继续临床保证的血管内治疗（ET）。试验的三个臂包括：RT-PA Plus安慰剂，RT-PA 加上Argatroban，RT-PA和Eptifibatide。受试者最初以1：1：1的比率随机分配，最高为150名受试者注册。响应自适应随机化将有利于看来最多的治疗臂根据累积数据有利。招募了500名受试者后，看似最多的治疗臂将选择有利的固定随机化与标准处理。固定随机化臂必须在500名受试者中选择。如果没有干预部门似乎单独使用RT-PA（<20％的预测概率）。临时分析也将在700和900进行主题。在这些时候，如果没有干预臂比RT-PA更好，则可能会停止审判单独（<5％的预测概率）；如果手臂看起来更好，则可能会提早停止审判比RT-PA（> 99％的预测概率）。主要的3个月效率端点由中央执行研究人员对治疗作业视而不见。其他终点将包括：（1）其他结果指标包括NIHSS，通过Euroqol EQ-5D在90天内测量的生活质量实用程序）；（2）早期回应由NIHSS在24小时时由0-2的NIHSS确定的治疗；（3）30天的MRS；（4）治疗差异在ET与非ET受试者中的影响；（5）治疗效果的种族/种族和性别差异。试验将得到三项Ninds合作协议的支持：（1）辛辛那提大学中风试验网络（NSTN）国家临床协调中心（PI：Joseph P. Broderick，MD）提供项目和站点管理；（2）到医疗的NSTN国家数据管理中心（NDMC）南卡罗来纳大学（PI：Yuko Y. Palesch，PhD）提供数据管理和统计专业知识；（3）PI项目的临床领导，现场招聘和研究行为和操作（多个PIS： Opeolu Adeoye，医学博士；马里兰州安德鲁·巴雷托（Andrew Barreto）；约瑟夫·布罗德里克（Joseph P. Broderick），医学博士；詹姆斯·格罗塔（James Grotta），医学博士）。