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改善中风治疗反应的策略 (SISTER)

2026年10月13日 更新者:Translational Sciences, Inc.

SISTER is a Phase-II, prospective, randomized, placebo-controlled, blinded, dose finding trial that aims to determine the safety and preliminary efficacy of TS23, a monoclonal antibody against the alpha-2 antiplasmin (a2-AP), in acute ischemic stroke.

研究概览

地位

招聘中

干预/治疗

详细说明

SISTER is a Phase II, Bayesian, adaptive, randomized, dose-finding trial of TS23 in patients with acute ischemic stroke. Patients with an anterior cerebral circulation acute ischemic stroke and present between 4.5 to 24 hours of their last known well with a presenting NIH Stroke Scale Score >/=4 (with the patient having a clearly disabling deficit if the NIHSS is 4 or 5) and an imaging evidence of salvageable brain tissue will be eligible and will be approached for an informed consent for study participation. Patients with an NIHSS of 4-5 must have a new, disabling neuro-logic deficit to be eligible for the study. After informed consent is provided, the study will randomize to 4 doses of TS23 and placebo. The trial will enroll up to 150 subjects at up to 70 participating US sites.

The effects of TS23 will be evaluated on two following primary outcomes using a utility function: 1) primary safety outcome: any intracerebral hemorrhage at 30 (+/-4) hours and 2) primary efficacy outcome: NIH Stroke Scale score at 30 (+/-4) hours after drug administration. The study will follow participants for 90 (+/-7) days.

Primary Objective: To identify a dose of TS23 that is safe and more efficacious than placebo for the treatment of patients from 4.5 to 24 hours of last known well, who have evidence of core-penumbra mismatch on perfusion imaging and are not a candidate for standard of care reperfusion therapies.

研究类型

介入性

注册 (估计的)

300

阶段

  • 阶段2

联系人和位置

本节提供了进行研究的人员的详细联系信息,以及有关进行该研究的地点的信息。

学习联系方式

研究联系人备份

学习地点

    • Alabama
      • Birmingham、Alabama、美国、35233
        • 招聘中
        • University of Alabama Hospital
        • 接触:
        • 首席研究员:
          • Felix Guerra Castanon, MD
    • Arizona
      • Phoenix、Arizona、美国、85006
        • 招聘中
        • Banner University Medical Center
        • 首席研究员:
          • Savdeep Singh, MD
        • 接触:
      • Phoenix、Arizona、美国、85054
        • 撤销
        • Mayo Clinic Phoenix
      • Tucson、Arizona、美国、85719
        • 招聘中
        • Banner University Medical Center - Tucson
        • 接触:
        • 首席研究员:
          • Firas Kaddouh, MD, MHS
    • California
      • La Jolla、California、美国、92093
      • Los Angeles、California、美国、90027
        • 招聘中
        • Kaiser Permanente Los Angeles
        • 接触:
        • 首席研究员:
          • Navdeep Sangha, MD
      • Sacramento、California、美国、95816
        • 撤销
        • Sutter Medical Center
      • San Diego、California、美国、92103
        • 招聘中
        • UCSD Medical Center- Hillcrest Hospital
        • 接触:
        • 首席研究员:
          • Royya Modir, MD
        • 接触:
    • Connecticut
      • Hartford、Connecticut、美国、06102
      • New Haven、Connecticut、美国、06511
        • 招聘中
        • Yale New Haven Hospital
        • 接触:
        • 首席研究员:
          • James Giles, MD, PhD
    • Delaware
      • Newark、Delaware、美国、19718
        • 撤销
        • Christiana Hospital
    • Florida
      • Gainesville、Florida、美国、32608
        • 终止
        • UF Health Shands Hospital
      • Miami、Florida、美国、33136
    • Georgia
      • Atlanta、Georgia、美国、30303
        • 招聘中
        • Grady Memorial Hospital
        • 接触:
        • 首席研究员:
          • Nicolas Bianchi, MD
    • Illinois
      • Chicago、Illinois、美国、60637
        • 主动,不招人
        • University of Chicago Medical Center
    • Iowa
      • Iowa City、Iowa、美国、52242
        • 撤销
        • University of Iowa Hospitals & Clinics
    • Kentucky
      • Lexington、Kentucky、美国、40503
      • Louisville、Kentucky、美国、40202
        • 招聘中
        • University of Louisville Hospital
        • 首席研究员:
          • Isaac Abecassis, MD
        • 接触:
    • Massachusetts
      • Boston、Massachusetts、美国、02115
        • 招聘中
        • Brigham and Women's Hospital
        • 首席研究员:
          • Rahul Mahajan, MD, PhD
        • 接触:
      • Boston、Massachusetts、美国、02171
        • 招聘中
        • Massachusetts General Hospital
        • 首席研究员:
          • Aneesh Singhal, MD, MBBS
        • 接触:
    • Minnesota
      • Burnsville、Minnesota、美国、55337
        • 招聘中
        • M Health Fairview Ridges Hospital
        • 接触:
        • 接触:
        • 首席研究员:
          • Muhammad Affan, MD, MBBS
      • Edina、Minnesota、美国、55435
        • 招聘中
        • M Health Fairview Southdale Hospital
        • 接触:
        • 首席研究员:
          • Muhammad Affan, MD, MBBS
        • 接触:
      • Minneapolis、Minnesota、美国、55455
        • 招聘中
        • M Health Fairview University of Minnesota Medical Center
        • 接触:
        • 接触:
        • 首席研究员:
          • Muhammad Affan, MD,MBBS
      • Saint Paul、Minnesota、美国、55102
        • 撤销
        • United Hospital
    • Missouri
      • St Louis、Missouri、美国、63110
        • 招聘中
        • Barnes Jewish Hospital
        • 首席研究员:
          • Charles Kircher, MD
        • 接触:
    • New Jersey
      • Edison、New Jersey、美国、08837
        • 招聘中
        • JFK Medical Center
        • 首席研究员:
          • Nancy Gadallah, DO
        • 接触:
    • New York
      • Brooklyn、New York、美国、11220
      • Buffalo、New York、美国、14203
        • 撤销
        • Buffalo General Medical Center
      • Manhasset、New York、美国、11030
      • New York、New York、美国、10029
        • 招聘中
        • The Mount Sinai Hospital
        • 接触:
        • 首席研究员:
          • Laura Stein, MD, MPH
      • New York、New York、美国、10032
      • New York、New York、美国、10029
        • 撤销
        • Mount Sinai West
      • Syracuse、New York、美国、13202
        • 招聘中
        • SUNY Upstate Medical University
        • 接触:
        • 首席研究员:
          • Julius-Gene LaTorre, MD, MPH
        • 接触:
      • Valhalla、New York、美国、10595
        • 撤销
        • Westchester Medical Center
    • North Carolina
      • Durham、North Carolina、美国、27710
      • Winston-Salem、North Carolina、美国、27157
        • 终止
        • Wake Forest Baptist Medical Center
    • Ohio
      • Cincinnati、Ohio、美国、45267
        • 招聘中
        • University of Cincinnati Medical Center
        • 首席研究员:
          • Yasmin Aziz, MD
        • 接触:
      • Columbus、Ohio、美国、43210
        • 招聘中
        • OSU Wexner Medical Center
        • 首席研究员:
          • Jan Bittar, MD
        • 接触:
    • Oklahoma
      • Tulsa、Oklahoma、美国、74104
    • Oregon
      • Portland、Oregon、美国、97225
        • 招聘中
        • Providence St. Vincent Medical Center
        • 首席研究员:
          • Kishan Patel, MD
        • 接触:
    • Pennsylvania
      • Bethlehem、Pennsylvania、美国、18015
        • 招聘中
        • Saint Luke's Hospital of Bethlehem Pennsylvania
        • 首席研究员:
          • Daniel Ackerman, MD
        • 接触:
      • Philadelphia、Pennsylvania、美国、19140
        • 招聘中
        • Temple University Hospital
        • 接触:
        • 首席研究员:
          • Nina Gentile, MD
    • Rhode Island
      • Providence、Rhode Island、美国、02903
        • 招聘中
        • Rhode Island Hospital
        • 首席研究员:
          • Farhan Khan, MD
        • 接触:
    • South Carolina
      • Charleston、South Carolina、美国、32608
        • 招聘中
        • Medical University of South Carolina University Hospital
        • 接触:
        • 接触:
        • 首席研究员:
          • Christine Holmstedt, DO
      • Greenville、South Carolina、美国、29605
    • Tennessee
      • Memphis、Tennessee、美国、38104
        • 招聘中
        • Methodist University Hospital
        • 接触:
        • 首席研究员:
          • Balaji Krishnaiah, MD
        • 接触:
    • Texas
    • Utah
      • Salt Lake City、Utah、美国、84132
        • 撤销
        • University of Utah Healthcare
    • Virginia
      • Charlottesville、Virginia、美国、22901
        • 招聘中
        • UVA Medical Center
        • 首席研究员:
          • Amna Sohail, MBBS, MD
        • 接触:
      • Richmond、Virginia、美国、23298
        • 撤销
        • VCU Medical Center
    • Washington
      • Seattle、Washington、美国、98104
        • 撤销
        • Harborview Medical Center
    • Wisconsin

参与标准

研究人员寻找符合特定描述的人,称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。

资格标准

适合学习的年龄

18年 及以上 (成人、年长者)

接受健康志愿者

不

有资格学习的性别

全部

描述

Inclusion Criteria:

  1. Age 18 years and older

  2. Suspected anterior circulation acute ischemic stroke

  3. NIH Stroke Scale score ≥4 prior to randomization

    a. The participant must have a clearly disabling deficit if NIHSS is 4-5.

  4. Favorable baseline neuroimaging consisting of all of the following:

    1. ASPECTS of 6 or more on CT (or ASPECTS of ≥7 on MRI)
    2. Favorable perfusion imaging on CT perfusion (CTP)/MR-perfusion weighted imaging (PWI) consisting of all of the following:

    i. Mismatch ratio of penumbra: core >1.2 ii. Mismatch volume >10 cc iii. Core <70 cc

    c. If CT hypodensity is present, then in the investigator's visual assessment, the total acute infarct volume combined area of (a) the CT hypodensity and (b) the perfusion-based core volume (CBF<30%) should be smaller than perfusion-based volume (area of Tmax>6s minus CBF<30%).

  5. Able to receive assigned study drug within 4.5 to 24 hours of stroke onset or last known well.

  6. Anticipate being able to receive assigned study drug within 120 minutes of qualifying perfusion imaging.

  7. Informed consent for the study participation obtained from participant or their legally authorized representatives.

Exclusion Criteria:

  1. Received endovascular treatment with clot engagement.

    1. Patients who undergo groin puncture but clot engagement is not attempted due to spontaneous distal migration are permitted to be enrolled in the trial if all other eligibility criteria are met.
    2. Patients who undergo groin puncture but clot is not engaged due to reasons other than spontaneous distal migration are NOT permitted.
  2. Received or planned to receive intravenous thrombolysis.

  3. Pre-stroke modified Rankin score >2.

  4. Previous treatment with TS23 or known previous allergy to antibody therapy.

  5. Known pregnancy, women who are breastfeeding or plan to breastfeed within 3 months of receiving TS23 or have a positive urine or serum pregnancy test for women of childbearing potential.

  6. Known previous stroke in the past 90 days.

  7. Known previous intracranial hemorrhage, intracranial neoplasm, subarachnoid hemorrhage, or arterial venous malformation.

  8. Known active diagnosis of intracranial neoplasm.

  9. Clinical presentation suggestive of a subarachnoid hemorrhage, even if initial CT scan was normal.

  10. Surgery or biopsy of parenchymal organ in the past 30 days.

  11. Known trauma with internal injuries or persistent ulcerative wounds in the past 30 days.

  12. Severe head trauma in the past 90 days.

  13. Persistent systolic blood pressure >180mmHg or diastolic blood pressure >105mmHg despite best medical management.

  14. Serious systemic hemorrhage in the past 30 days.

  15. Known hereditary or acquired hemorrhagic diathesis, coagulation factor deficiency, or oral anticoagulant therapy with International Normalized Ratio (INR) >1.7.

  16. Platelets <100,000/mm3.

  17. Hematocrit <25 %.

  18. Elevated aPTT above laboratory upper limit of normal.

  19. Creatinine > 4 mg/dl, or patients receiving renal dialysis, regardless of creatinine.

  20. Received the following within the previous 24 hours:

    1. If patient received unfractionated heparin within the last 24 hours, the patient must have an aPTT within normal range prior to enrollment.
    2. Low molecular weight heparins such as Dalteparin, enoxaparin, tinzaparin in full dose within the previous 24 hours.
  21. Received Factor Xa inhibitors (such as Fondaparinux, apixaban or rivaroxaban) within the past 48 hours.

  22. Received direct thrombin inhibitors (e.g., argatroban, dabigatran, bivalirudin, desirudin, lepirudin) within 48 hours.

  23. Received glycoprotein IIb/IIIa inhibitors within the past 14 days.

  24. Known pre-existing neurological or psychiatric disease which would confound the neurological/functional evaluations.

  25. Current participation in another research drug treatment protocol (i.e., participants could not start another experimental agent until after 90 days).

  26. Concurrent acute myocardial infarction, pulmonary embolism, deep venous thrombosis or other thrombotic event that requires anticoagulation or anti-platelet treatment.

学习计划

本节提供研究计划的详细信息,包括研究的设计方式和研究的衡量标准。

研究是如何设计的?

设计细节

  • 主要用途:治疗
  • 分配:随机化
  • 介入模型:并行分配
  • 屏蔽:四人间

武器和干预

参与者组/臂
干预/治疗
安慰剂比较:Placebo

Placebo

Monoclonal antibody

实验性的:Dose 1 TS23

low dose

Monoclonal antibody

实验性的:Dose 2 TS23

next higher dose

Monoclonal antibody

实验性的:Dose 3 TS23

next higher dose

Monoclonal antibody

实验性的:Dose 4 TS23

highest dose

Monoclonal antibody

研究衡量的是什么?

主要结果指标

结果测量
措施说明
大体时间
The proportion of patients with ANY intracerebral hemorrhage (ICH)
大体时间:At 30 (+/- 4) hours after study drug

Any ICH visualized on the follow-up CT scan

At 30 (+/- 4) hours after study drug
Stroke severity as measured by the National Institutes of Health Stroke Scale (NIHSS)
大体时间:At 30 (+/- 4) hours after study drug

NIHSS is a stroke severity score that ranges from 0 to 42, with higher numbers indicating a more severe stroke. The NIHSS will be adjusted for the baseline value in analysis.

At 30 (+/- 4) hours after study drug

次要结果测量

结果测量
措施说明
大体时间
Improvement in level of global disability measured by modified Rankin Score (mRS distribution)
大体时间:90 (±7) days

The modified Rankin Score assessment is a 7-level disability scale that measures the degree of disability or dependence in daily activities of people who have suffered a stroke. Range 0= no disability and 6=dead.

90 (±7) days
Frequency of Modified Rankin (mRS) score of 0-1 or returning to pre-stroke mRS.
大体时间:Proportion of patients with modified Rankin scale score 0-1 or return to pre-stroke mRS at 90 (+/-7) days.

Proportion of patients with modified Rankin scale score 0-1 or return to pre-stroke mRS.

Proportion of patients with modified Rankin scale score 0-1 or return to pre-stroke mRS at 90 (+/-7) days.
NIHSS
大体时间:72 (±12) hours (or at discharge if sooner) after study drug administration.

NIHSS is a stroke severity score that ranges from 0 to 42, with higher numbers indicating a more severe stroke. The NIHSS will be adjusted for the baseline value in analysis.

72 (±12) hours (or at discharge if sooner) after study drug administration.
α2-antiplasmin (a2AP) level in plasma
大体时间:at 3 (±1) h after completion of study drug administration

A serine protease inhibitor responsible for inactivating plasmin.

at 3 (±1) h after completion of study drug administration
Matrix metalloproteinase-9 level in plasma
大体时间:3 (±1) h after completion of study drug

An enzyme that regulates the pathological remodeling process that involve inflammation and fibrosis associated with cardiovascular disease.

3 (±1) h after completion of study drug
% brain tissue reperfusion
大体时间:30 (±4) h after study drug administration

Proportion of brain tissue that is reperfused on the follow-up perfusion scan compared to the baseline, calculated as:

([baseline minus follow up perfusion imaging area of hypoperfusion]/ baseline area of hypoperfusion); hypoperfusion=T max>6 seconds

30 (±4) h after study drug administration
Pharmacokinetic analyses
大体时间:3 (±1) h, 30 (±4) h, 30 (±5) days & 90 (±7) days after study drug administration. At 90 (±7) days for approximately 50 mITT participants. After approximately 50 mITT participants, it will be obtained at 72h(+12 hrs)/discharge visit, whichever comes 1st.

Measure of plasma concentrations of TS23

3 (±1) h, 30 (±4) h, 30 (±5) days & 90 (±7) days after study drug administration. At 90 (±7) days for approximately 50 mITT participants. After approximately 50 mITT participants, it will be obtained at 72h(+12 hrs)/discharge visit, whichever comes 1st.
Evaluation of anti-drug antibodies
大体时间:will be measured at baseline and 90 (±7) days follow-up visit for approximately 50 mITT participants.

commonly used for characterization of therapeutic antibodies

will be measured at baseline and 90 (±7) days follow-up visit for approximately 50 mITT participants.
Proportion of patients with symptomatic intracerebral hemorrhage
大体时间:30 (±4) h of study drug administration

a blood clot large enough to cause significant neurological deterioration.

30 (±4) h of study drug administration
Proportion of patients with non-intracerebral hemorrhage major or clinically relevant non-major bleeding
大体时间:30 days of study drug administration.

major and non-major events of bleeding that is not in the brain

30 days of study drug administration.
Plasma fibrinogen level
大体时间:3 (±1) h after completion of study drug

Clotting factor

3 (±1) h after completion of study drug
Proportion of patients with non-bleeding severe adverse events
大体时间:90 (±7) days

Assessment of untoward events

90 (±7) days
Proportion of patients with stroke-related and all-cause deaths
大体时间:90 (±7) days

measure of important patient outcomes

90 (±7) days

合作者和调查者

在这里您可以找到参与这项研究的人员和组织。

研究记录日期

这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查,以确保它们在发布到公共网站之前符合特定的质量控制标准。

研究主要日期

学习开始 (实际的)

2024年3月18日

初级完成 (估计的)

2028年7月1日

研究完成 (估计的)

2028年12月1日

研究注册日期

首次提交

2023年7月8日

首先提交符合 QC 标准的

2023年7月8日

首次发布 (实际的)

2023年7月17日

研究记录更新

最后更新发布 (实际的)

2026年10月19日

上次提交的符合 QC 标准的更新

2026年10月13日

最后验证

2026年10月1日

更多信息

与本研究相关的术语

其他研究编号

  • TS23-U202
  • UH3NS125023 (美国 NIH 拨款/合同)

计划个人参与者数据 (IPD)

计划共享个人参与者数据 (IPD)?

是的

IPD 计划说明

The SISTER trial will comply with the NIH Public Access Policy, which ensures that the public has access to the published results of NIH funded research, and the StrokeNet SOP (ADM 03) regarding results publication. Manuscripts and abstracts that use data from SISTER require approval from the Publication Committee of an original proposal before the concept may proceed. All publications will include this acknowledgement: "Research reported in this publication was supported by the National Institute of Neurological Disorders and Stroke of the National Institutes of Health under Award Number [to be determined]. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health."

药物和器械信息、研究文件

研究美国 FDA 监管的药品

是的

研究美国 FDA 监管的设备产品

不

此信息直接从 clinicaltrials.gov 网站检索,没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求,请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改,我们的网站上也会自动更新.

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