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ClinicalTrials.gov ID

NCT07476898

Lead Sponsor

First Hospital of China Medical UniversityOTHER

Overall Status

Not yet recruiting

Study Type

Interventional

Phase

Phase 3

Enrollment

864Estimated

Last Update Posted

Mar 17, 2026Actual

Start Date

Mar 1, 2026Estimated

Primary Completion Date

Jul 1, 2028Estimated

Completion Date

Aug 1, 2028Estimated

Official Title

A Multicenter, Randomized, Open-Label, Blinded-Endpoint Trial of Tenecteplase Versus Dual Antiplatelet Therapy in Mild Disabling Ischemic Stroke With Large Vessel Occlusion Beyond 4.5 Hours (TIME-MINOR Trial)

Brief Summary

To verify the efficacy and safety of intravenous tenecteplase (TNK) in patients with disabling minor stroke and large vessel occlusion (LVO) within a 4.5-24 hour time window.

Detailed Description

Stroke is a leading cause of death and disability. Minor stroke (NIHSS ≤5) accounts for 48% of ischemic strokes, with its "mild symptom" presentation masking the potential risk of disability. About 30% of patients have poor 90-day outcomes (mRS ≥2) due to disabling deficits (e.g., unilateral limb weakness ≥2, aphasia, or hemianopia), resulting not only in loss of personal independence but also a surge in family and social medical expenses. Notably, up to 55% of patients present beyond the standard time window (4.5-24 hours). Having missed the golden window for thrombolysis, they are often relegated to conservative treatment. When complicated by large vessel occlusion (LVO), the recanalization rate with dual antiplatelet therapy (DAPT) alone is less than 5%, creating a "silent epidemic" of accumulating disability risk.

The PRISMS trial showed no benefit of thrombolysis within 4.5 hours in non-disabling stroke, but due to the exclusion of the LVO subgroup and early termination (actual enrollment only 313), the potential benefit for disabling patients remains an open question. The TEMPO-2 trial found increased mortality (5% vs 1%) in patients receiving tenecteplase (TNK) without selecting for ischemic penumbra, potentially masking recanalization benefits in certain subgroups (e.g., those with mismatch ratio ≥1.8). A subgroup analysis of TEMPO-2 for onset 4.5-12h, minor disabling stroke (median NIHSS 4), showed a 3-month mRS 0-1 rate of 61.7% in the tenecteplase group vs. 47.2% in the standard care group, but this was not statistically significant due to the small subgroup size. While CHANCE series studies confirmed that DAPT reduces the risk of stroke recurrence by 33%, it is ineffective for LVO recanalization, leaving disability rates high.

The 2023 "Chinese Guidelines for Clinical Management of Cerebrovascular Diseases" and the European Stroke Organisation (ESO) guidelines explicitly state that treatment for disabling minor stroke with LVO beyond the time window (4.5-24 hours) lacks a Class I recommendation (Evidence Level C), leaving clinical decision-making in a dilemma without evidence-based guidance.

DAWN/DEFUSE-3/TRACE Ⅲ studies validated the value of imaging selection in thrombectomy, but they excluded patients with NIHSS ≤5, leaving a gap in penumbra assessment criteria for minor stroke.

Therefore, the investigators designed the TIME-MINOR trial to evaluate whether intravenous tenecteplase, guided by multimodal imaging, can improve outcomes in patients with NIHSS ≤5 and LVO presenting 4.5-24 hours after onset.

• Stroke

• Tenecteplase (0.25mg/kg)
• Standard Medical Management

Ages Eligible for Study

Adult (18-64)Older Adult (65+)

Sexes Eligible for Study

All

Accepts Healthy Volunteers

No

Eligibility Criteria

Inclusion Criteria:

• Male or female subjects (age ≥ 18 years).
• Diagnosis of acute ischemic stroke, with intracranial hemorrhage ruled out by CT or MRI.
• Time from stroke onset or last known well to randomization is 4.5 to 24 hours.
• NIHSS score 2-5 and meeting the definition of disabling deficit: complete hemianopia (NIHSS question 3 score ≥ 2); severe aphasia (NIHSS question 9 score ≥ 2); neglect (NIHSS question 11 score ≥ 1); any persistent limb weakness against gravity (NIHSS question 6 or 7 score ≥ 2); any functional deficit considered potentially disabling by the physician and patient, such as inability to perform basic activities of daily living (bathing, independent walking, toileting, personal hygiene, and eating) or return to work.
• LVO (internal carotid artery, middle cerebral artery M1/M2 segments) confirmed by CTA or MRA, including tandem lesions.
• Core infarct volume < 70 ml, ischemic penumbra volume ≥ 15 ml, and mismatch ratio ≥ 1.8, as shown by CTP or MRI+MRP.
• Written informed consent.

Exclusion Criteria:

• Significant pre-stroke neurological deficit (pre-stroke mRS ≥ 2).
• History of stroke within the last 3 months.
• History of intracranial hemorrhage.
• Suspected subarachnoid hemorrhage.
• Intracranial tumor, vascular malformation, or aneurysm.
• Major surgery within the last 1 month.
• Systolic blood pressure ≥ 180 mmHg or diastolic blood pressure ≥ 110 mmHg.
• Platelet count < 10⁵/mm³.
• Heparin or oral anticoagulant therapy within 48 hours.
• Abnormal APTT.
• Thrombin or factor Xa inhibitors.
• Severe illness with life expectancy < 3 months.
• Blood glucose < 50 mg/dL (2.7 mmol/L).
• Participation in any other investigational drug or device study within the last 3 months.
• Pregnancy.
• Patients deemed unsuitable for the registry study by the investigator.

Primary Purpose

Treatment

Allocation

Randomized

Interventional Model

Parallel Assignment

Masking

None (Open Label)

Lead Sponsor

First Hospital of China Medical UniversityOTHER

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