Strategy for Improving Stroke Treatment Response (SISTER)

March 27, 2026 updated by: Translational Sciences, Inc.

Strategy for Improving Stroke Treatment Response (SISTER) Trial

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

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. After informed consent is provided, the study will randomize to 4 doses of TS23 and placebo. The trial will enroll up to 300 subjects at up to 60 participating US sites and up to 17 Canadian 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.

Study Type

Interventional

Enrollment (Estimated)

300

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35233
        • Recruiting
        • University of Alabama Hospital
        • Contact:
        • Principal Investigator:
          • Felix Guerra Castanon, MD
    • Arizona
      • Phoenix, Arizona, United States, 85006
        • Recruiting
        • Banner University Medical Center
        • Principal Investigator:
          • Savdeep Singh, MD
        • Contact:
      • Phoenix, Arizona, United States, 85054
        • Withdrawn
        • Mayo Clinic Phoenix
      • Tucson, Arizona, United States, 85719
        • Not yet recruiting
        • Banner University Medical Center - Tucson
        • Contact:
        • Principal Investigator:
          • Firas Kaddouh, MD, MHS
    • California
      • La Jolla, California, United States, 92093
      • Los Angeles, California, United States, 90027
        • Recruiting
        • Kaiser Permanente Los Angeles
        • Contact:
        • Principal Investigator:
          • Navdeep Sangha, MD
      • Sacramento, California, United States, 95816
        • Withdrawn
        • Sutter Medical Center
      • San Diego, California, United States, 92103
        • Recruiting
        • UCSD Medical Center- Hillcrest Hospital
        • Contact:
        • Principal Investigator:
          • Royya Modir, MD
        • Contact:
    • Connecticut
      • Hartford, Connecticut, United States, 06102
      • New Haven, Connecticut, United States, 06511
        • Recruiting
        • Yale New Haven Hospital
        • Contact:
        • Principal Investigator:
          • James Giles, MD, PhD
    • Delaware
      • Newark, Delaware, United States, 19718
        • Recruiting
        • Christiana Hospital
        • Principal Investigator:
          • Jason Nomura, MD
        • Contact:
    • Florida
      • Gainesville, Florida, United States, 32608
        • Terminated
        • UF Health Shands Hospital
      • Miami, Florida, United States, 33136
    • Georgia
      • Atlanta, Georgia, United States, 30303
        • Recruiting
        • Grady Memorial Hospital
        • Contact:
        • Principal Investigator:
          • Nicolas Bianchi, MD
    • Illinois
      • Chicago, Illinois, United States, 60637
        • Recruiting
        • University of Chicago Medical Center
        • Contact:
        • Principal Investigator:
          • James Siegler, MD, FAHA
    • Iowa
      • Iowa City, Iowa, United States, 52242
        • Withdrawn
        • University of Iowa Hospitals & Clinics
    • Kentucky
      • Lexington, Kentucky, United States, 40503
      • Louisville, Kentucky, United States, 40202
        • Recruiting
        • University of Louisville Hospital
        • Principal Investigator:
          • Isaac Abecassis, MD
        • Contact:
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Recruiting
        • Brigham and Women's Hospital
        • Principal Investigator:
          • Rahul Mahajan, MD, PhD
        • Contact:
      • Boston, Massachusetts, United States, 02171
        • Recruiting
        • Massachusetts General Hospital
        • Principal Investigator:
          • Aneesh Singhal, MD, MBBS
        • Contact:
    • Minnesota
      • Burnsville, Minnesota, United States, 55337
        • Recruiting
        • M Health Fairview Ridges Hospital
        • Contact:
        • Contact:
        • Principal Investigator:
          • Muhammad Affan, MD, MBBS
      • Edina, Minnesota, United States, 55435
        • Recruiting
        • M Health Fairview Southdale Hospital
        • Contact:
        • Principal Investigator:
          • Muhammad Affan, MD, MBBS
        • Contact:
      • Minneapolis, Minnesota, United States, 55455
        • Recruiting
        • M Health Fairview University of Minnesota Medical Center
        • Contact:
        • Contact:
        • Principal Investigator:
          • Muhammad Affan, MD,MBBS
      • Saint Paul, Minnesota, United States, 55102
        • Withdrawn
        • United Hospital
    • Missouri
      • St Louis, Missouri, United States, 63110
        • Recruiting
        • Barnes Jewish Hospital
        • Principal Investigator:
          • Charles Kircher, MD
        • Contact:
    • New Jersey
      • Edison, New Jersey, United States, 08837
        • Recruiting
        • JFK Medical Center
        • Principal Investigator:
          • Nancy Gadallah, DO
        • Contact:
    • New York
      • Brooklyn, New York, United States, 11220
      • Buffalo, New York, United States, 14203
        • Withdrawn
        • Buffalo General Medical Center
      • Manhasset, New York, United States, 11030
      • New York, New York, United States, 10029
        • Recruiting
        • The Mount Sinai Hospital
        • Contact:
        • Principal Investigator:
          • Laura Stein, MD, MPH
      • New York, New York, United States, 10032
      • New York, New York, United States, 10029
        • Recruiting
        • Mount Sinai West
        • Contact:
        • Principal Investigator:
          • Laura Stein, MD, MPH
      • Syracuse, New York, United States, 13202
        • Recruiting
        • SUNY Upstate Medical University
        • Contact:
        • Principal Investigator:
          • Julius-Gene LaTorre, MD, MPH
        • Contact:
      • Valhalla, New York, United States, 10595
        • Not yet recruiting
        • Westchester Medical Center
        • Contact:
        • Principal Investigator:
          • Gurmeen Kaur, MD
    • North Carolina
      • Durham, North Carolina, United States, 27710
      • Winston-Salem, North Carolina, United States, 27157
        • Terminated
        • Wake Forest Baptist Medical Center
    • Ohio
      • Cincinnati, Ohio, United States, 45267
        • Recruiting
        • University of Cincinnati Medical Center
        • Principal Investigator:
          • Yasmin Aziz, MD
        • Contact:
      • Columbus, Ohio, United States, 43210
        • Recruiting
        • OSU Wexner Medical Center
        • Principal Investigator:
          • Jan Bittar, MD
        • Contact:
    • Oklahoma
      • Tulsa, Oklahoma, United States, 74104
    • Oregon
      • Portland, Oregon, United States, 97225
        • Recruiting
        • Providence St. Vincent Medical Center
        • Principal Investigator:
          • Kishan Patel, MD
        • Contact:
    • Pennsylvania
      • Bethlehem, Pennsylvania, United States, 18015
        • Recruiting
        • Saint Luke's Hospital of Bethlehem Pennsylvania
        • Principal Investigator:
          • Daniel Ackerman, MD
        • Contact:
      • Philadelphia, Pennsylvania, United States, 19140
        • Recruiting
        • Temple University Hospital
        • Contact:
        • Principal Investigator:
          • Nina Gentile, MD
    • Rhode Island
      • Providence, Rhode Island, United States, 02903
        • Recruiting
        • Rhode Island Hospital
        • Principal Investigator:
          • Farhan Khan, MD
        • Contact:
    • South Carolina
      • Charleston, South Carolina, United States, 32608
        • Recruiting
        • Medical University of South Carolina University Hospital
        • Contact:
        • Contact:
        • Principal Investigator:
          • Christine Holmstedt, DO
      • Greenville, South Carolina, United States, 29605
    • Tennessee
      • Memphis, Tennessee, United States, 38104
        • Recruiting
        • Methodist University Hospital
        • Contact:
        • Principal Investigator:
          • Balaji Krishnaiah, MD
        • Contact:
    • Texas
    • Utah
      • Salt Lake City, Utah, United States, 84132
        • Withdrawn
        • University of Utah Healthcare
    • Virginia
      • Charlottesville, Virginia, United States, 22901
        • Recruiting
        • UVA Medical Center
        • Principal Investigator:
          • Amna Sohail, MBBS, MD
        • Contact:
      • Richmond, Virginia, United States, 23298
        • Not yet recruiting
        • VCU Medical Center
        • Principal Investigator:
          • Shraddha Mainali, MD
        • Contact:
    • Washington
      • Seattle, Washington, United States, 98104
        • Recruiting
        • Harborview Medical Center
        • Contact:
        • Principal Investigator:
          • David Tirschwell, MD, MSc.
    • Wisconsin

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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. 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.

    • Study drug administration is encouraged within 90 minutes after qualifying perfusion image but is allowed up to 120 minutes. After 120 minutes, another perfusion image to ensure that inclusion criteria are met is required.

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo
Biological: TS23
Monoclonal antibody
Experimental: Dose 1 TS23
low dose
Biological: TS23
Monoclonal antibody
Experimental: Dose 2 TS23
next higher dose
Biological: TS23
Monoclonal antibody
Experimental: Dose 3 TS23
next higher dose
Biological: TS23
Monoclonal antibody
Experimental: Dose 4 TS23
highest dose
Biological: TS23
Monoclonal antibody

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The proportion of patients with ANY intracerebral hemorrhage (ICH)
Time Frame: 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)
Time Frame: 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

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Improvement in level of global disability measured by modified Rankin Score (mRS distribution)
Time Frame: 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
NIHSS
Time Frame: 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
Time Frame: 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
Time Frame: 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
Plasma fibrinogen level
Time Frame: 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
Time Frame: 90 (±7) days
Assessment of untoward events
90 (±7) days
Proportion of patients with stroke-related and all-cause deaths
Time Frame: 90 (±7) days
measure of important patient outcomes
90 (±7) days
% brain tissue reperfusion
Time Frame: 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
Proportion of patients with non-intracerebral hemorrhage major or clinically relevant non-major bleeding
Time Frame: 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.
Frequency of Modified Rankin (mRS) score of 0-1 or returning to pre-stroke mRS.
Time Frame: 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.
Proportion of patients with symptomatic intracerebral hemorrhage
Time Frame: 30 (±4) h of study drug administration
a blood clot large enough to cause significant neurological deterioration.
30 (±4) h of study drug administration
Evaluation of anti-drug antibodies
Time Frame: 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.
Pharmacokinetic analyses
Time Frame: 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.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Translational Sciences, Inc.

Collaborators

Medical University of South Carolina
National Institute of Neurological Disorders and Stroke (NINDS)
University of Cincinnati
University of Arizona

Investigators

  • Principal Investigator: Eva Mistry, MBBS, University of Cincinnati

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 18, 2024

Primary Completion (Estimated)

July 1, 2027

Study Completion (Estimated)

December 1, 2027

Study Registration Dates

First Submitted

July 8, 2023

First Submitted That Met QC Criteria

July 8, 2023

First Posted (Actual)

July 17, 2023

Study Record Updates

Last Update Posted (Actual)

March 30, 2026

Last Update Submitted That Met QC Criteria

March 27, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • TS23-U202
  • UH3NS125023 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

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."

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Ischemic Stroke

Clinical Trials on TS23

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Zambia

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe