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：
10384272
负责人：
Opeolu M Adeoye
金额：
$ 699.76万
依托单位：
WASHINGTON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-05-01 至 2024-10-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10384272
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 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 efficacy outcomes endovascular thrombectomy 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).

中风溶栓多臂优化 (MOST) 中风试验将是一项双盲多中心、最多 1200 名受试者的随机对照 3 期试验将确定是否为成人（年龄≥18 岁）。年）基线时 NIH 卒中量表评分≥6 的受试者在症状出现后三小时内接受治疗 rt-PA 继之以阿加曲班或依替巴肽更有可能在 3 个月时获得良好的结果 (mRS)，因为与仅接受标准 IV rt-PA 治疗的受试者相比，所有治疗组中的受试者均可继续进行。临床需要的血管内治疗 (ET) 试验的三个组包括：rt-PA 加安慰剂、rt-PA。加阿加曲班和 rt-PA 加依替巴肽受试者最初以 1:1:1 的比例随机分配，最多 150 名受试者。然后，响应适应性随机化将有利于看起来最有效的治疗组。根据累积数据，在 500 名受试者入组后，出现最多的治疗组。必须选择固定随机分组与标准随机分组有利。如果没有干预组，则可以在 500 名受试者中选择试验，以便在 500 名受试者中发挥作用。似乎比单独使用 rt-PA 更好（<20% 预测概率）也将在 700 和 900 时进行。在这些时候，如果没有干预措施比 rt-PA 更好，试验可能会因徒劳而停止。单独使用（<5% 预测概率）；如果某一组的疗效似乎更好，则可能会提前停止试验与 rt-PA 相比（>99% 的预测概率），主要 3 个月疗效终点由中心执行。对治疗分配不知情的研究人员将包括：（1）其他结果指标。 (2) 及早响应 24 小时时 NIHSSS 确定为 0-2 的治疗；(3) 30 天时的 mRS；(4) 治疗中的差异； ET 与非 ET 受试者的效果；(5) 治疗效果的种族/民族和性别差异。将获得三项 NINDS 合作协议赠款的支持：(1) 辛辛那提大学 NINDS 中风试验网络 (NSTN) 国家临床协调中心（PI：Joseph P. Broderick，医学博士）提供项目和现场管理；(2) 位于医疗中心的 NSTN 国家数据管理中心 (NDMC) 南卡罗来纳大学（PI：Yuko Y. Palesch，博士）提供数据管理和统计专业知识； (3) 项目 PI 负责临床领导、研究中心招募以及研究实施和运营（多个 PI： Opeolu Adeoye，医学博士；Andrew Barreto，医学博士；Joseph P. Broderick，医学博士；James Grotta，医学博士）。

项目成果

期刊论文数量（1）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

The multiarm optimization of stroke thrombolysis phase 3 acute stroke randomized clinical trial: Rationale and methods.

卒中溶栓3期急性卒中随机临床试验的多臂优化：基本原理和方法。

DOI：
发表时间：
2021
期刊：
影响因子：
0
作者：
Deeds, S Iris;Barreto, Andrew;Elm, Jordan;Derdeyn, Colin P;Berry, Scott;Khatri, Pooja;Moy, Claudia;Janis, Scott;Broderick, Joseph;Grotta, James;Adeoye, Opeolu
通讯作者：
Adeoye, Opeolu