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.
Eligibility
Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
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.
Primary outcome measure(s)
The proportion of patients with ANY intracerebral hemorrhage (ICH) — At 30 (+/- 4) hours after study drug Any ICH visualized on the follow-up CT scan
Stroke severity as measured by the National Institutes of Health Stroke Scale (NIHSS) — 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.
Trial sites (52)
Facility
City
Region
Status
University of Alabama Hospital
Birmingham
Alabama
Recruiting
Banner University Medical Center
Phoenix
Arizona
Recruiting
Mayo Clinic Phoenix
Phoenix
Arizona
Withdrawn
Banner University Medical Center - Tucson
Tucson
Arizona
Recruiting
UCSD Health La Jolla
La Jolla
California
Recruiting
Kaiser Permanente Los Angeles
Los Angeles
California
Recruiting
Sutter Medical Center
Sacramento
California
Withdrawn
UCSD Medical Center- Hillcrest Hospital
San Diego
California
Recruiting
Hartford Hospital
Hartford
Connecticut
Recruiting
Yale New Haven Hospital
New Haven
Connecticut
Recruiting
Christiana Hospital
Newark
Delaware
Active Not Recruiting
UF Health Shands Hospital
Gainesville
Florida
Terminated
Jackson Memorial Hospital
Miami
Florida
Recruiting
Grady Memorial Hospital
Atlanta
Georgia
Recruiting
University of Chicago Medical Center
Chicago
Illinois
Recruiting
University of Iowa Hospitals & Clinics
Iowa City
Iowa
Withdrawn
Baptist Healthcare System, Inc.
Lexington
Kentucky
Recruiting
University of Louisville Hospital
Louisville
Kentucky
Recruiting
Brigham and Women's Hospital
Boston
Massachusetts
Recruiting
Massachusetts General Hospital
Boston
Massachusetts
Recruiting
M Health Fairview Ridges Hospital
Burnsville
Minnesota
Recruiting
M Health Fairview Southdale Hospital
Edina
Minnesota
Recruiting
M Health Fairview University of Minnesota Medical Center
Minneapolis
Minnesota
Recruiting
United Hospital
Saint Paul
Minnesota
Withdrawn
Barnes Jewish Hospital
St Louis
Missouri
Recruiting
JFK Medical Center
Edison
New Jersey
Recruiting
NYU Langone Health
Brooklyn
New York
Recruiting
Buffalo General Medical Center
Buffalo
New York
Withdrawn
North Shore University Hospital
Manhasset
New York
Recruiting
Mount Sinai West
New York
New York
Recruiting
The Mount Sinai Hospital
New York
New York
Recruiting
NYP Columbia University Medical Center
New York
New York
Recruiting
SUNY Upstate Medical University
Syracuse
New York
Recruiting
Westchester Medical Center
Valhalla
New York
Withdrawn
Duke University Hospital
Durham
North Carolina
Recruiting
Wake Forest Baptist Medical Center
Winston-Salem
North Carolina
Terminated
University of Cincinnati Medical Center
Cincinnati
Ohio
Recruiting
OSU Wexner Medical Center
Columbus
Ohio
Recruiting
Ascension St. John
Tulsa
Oklahoma
Recruiting
Providence St. Vincent Medical Center
Portland
Oregon
Recruiting
+ 12 more sites — see the full list on the official registry below.
More Translational Sciences, Inc. trials in the USA
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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