Clinical trial NCT06994975: CHinese Acute Tissue-Based Imaging Selection for Lysis In Stroke -Non-contrast CT Based EXtended Window Thrombolysis
Official title: CHinese Acute Tissue-Based Imaging Selection for Lysis In Stroke -Non-contrast CT Based EXtended Window Thrombolysis
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE3
Conditions: Acute Ischemic Stroke
Lead sponsor: Huashan Hospital
Sponsor class: OTHER
First posted: 2025-05-29
Enrollment: 890
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Multicenter, open-label, blinded-endpoint, randomized, controlled, phase 3 trial
Primary purpose: TREATMENT

Brief summary: The CHABLIS-NEXT trial is a multicenter, open-label, blinded-endpoint, randomized, controlled, phase 3 trial. The primary objective of this study is to explore the efficacy and safety of the dose of 0.25 mg/kg tenecteplase (TNK) in Chinese acute ischemic stroke (AIS) patients without substantial infarction on non-contrast computed tomography (NCCT) in an extended time window.

Detailed description: CHinese Acute tissue-Based imaging selection for Lysis In Stroke-Non-contrast CT based EXtended window Thrombolysis (CHABLIS-NEXT) is a multicenter, open-label, blinded-endpoint, randomized, controlled, phase 3 study. Patients with acute strokes who are unable to undergo endovascular thrombectomy and exhibit no substantial infarction lesion on non-contrast computed tomography (less than 50 mL according to the automated NCCT post-processing model and no visible hypodensity in more than 1/3 of the middle cerebral artery \[MCA\] territory) are randomly assigned in a 1:1 ratio to receive either 0.25 mg/kg TNK or standard medical treatment. The efficacy and safety of 0.25 mg/kg TNK are assessed through clinical prognosis at 90 days.

Eligibility criteria: Inclusion Criteria:

1. Suspected acute ischemic stroke of anterior cerebral circulation.
2. Last known well time \>4.5 hours and ≤24 hours.
3. Age ≥18 years old.
4. Baseline NIHSS (National Institutes of Health Stroke Scale) score \>5.
5. Premorbid modified Rankin Scale (mRS) ≤1.
6. Imaging criteria: Automated infarct segmentation by NCCT post-processing model indicates infarct core volume \<50 mL with no visible hypodensity in \>1/3 of the MCA territory.
7. Informed consent signed by the patient or the patient's legally authorized representative.

Exclusion Criteria:

1. Endovascular thrombectomy (EVT) planned at the time of randomization.
2. Allergy to the test drug and its ingredients.
3. Rapidly improving symptoms at the discretion of the investigator, which may indicate spontaneous recanalization.
4. Any sign of an acute intracranial hemorrhage or subarachnoid hemorrhage identified on baseline NCCT.
5. History of any intracranial hemorrhage.
6. History of ischemic stroke or major head trauma within the last 3 months.
7. History of intracranial/intraspinal surgery during the last 3 months.
8. Gastrointestinal malignancy or gastrointestinal bleeding within 21 days.
9. Known bleeding diatheses; platelets count \< 100000/mm3, international normalized ratio \> 1.7, prothrombin time \> 15 s, or activated partial thromboplastin clotting time \> 40 s.
10. Treatment with a full dosage of low-molecular weighted heparin in the last 24 hours.
11. Treatment with direct thrombin inhibitors or direct factor Xa inhibitors within the previous 48 hours unless the laboratory test of coagulation function is normal.
12. Initial systolic blood pressure ≥180 mmHg or diastolic blood pressure ≥100 mmHg.
13. Initial glucose levels \<2.8 or 22.22 mmol/L.
14. Known or suspected aortic arch dissection.

In addition to:

1. Clinical presentation or imaging profile consistent with Moyamoya disease/syndrome.
2. Pregnancy or breastfeeding.
3. Recent participation in another investigational drug or device study or registry in the past 30 days before enrollment.
4. Any terminal illness such that the patient would not be expected to survive more than three months.
5. Other conditions in which investigators believe that participating in this study may be harmful to the patient.

Primary outcomes:
measure: Proportion of Participants Achieving Excellent Functional Outcome (mRS 0-1) at 90±7 Days
timeFrame: at 90±7 days
Secondary outcomes:
measure: Infarct Growth Volume at 3-5 Days Compared to Baseline Core
timeFrame: at 3-5 days
measure: Proportion of Participants Achieving Good Functional Outcome (mRS 0-2) at 90±7 Days
timeFrame: at 90±7 days
measure: Distribution of Modified Rankin Scale Scores at 90±7 Days
timeFrame: at 90±7 days
measure: Proportion of Participants with Significant Neurological Improvement within 24-48 Hours
timeFrame: within 24-48 hours
measure: Change in NIHSS Score at 24-48 Hours
timeFrame: at 24-48 hours
measure: Incidence of Symptomatic Intracranial Hemorrhage within 24-48 Hours
timeFrame: within 24-48 hours
measure: Incidence of Any Intracranial Hemorrhage within 24-48 Hours Post Treatment
timeFrame: at 24-48 hours
measure: Incidence of PH2 within 24-48 Hours Post Treatment
timeFrame: at 24-48 hours
measure: Incidence of All-Cause Mortality within 90 Days
timeFrame: within 90 days
measure: Proportion of Participants with Poor Functional Outcome (mRS 5-6) at 90±7 Days
timeFrame: at 90±7 days
measure: Incidence of Systemic Bleeding within 90 Days
timeFrame: within 90 days
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Huashan Hospital, Fudan University
Study officials:
References: