Precision Reperfusion Therapy for Disabling Minor Stroke With Large Vessel Occlusion Beyond Time Window (TIME-MINOR)

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)

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Stroke
• Intervention / Treatment: Drug: Tenecteplase (0.25mg/kg); Drug: Standard Medical Management

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.

• Study Type: Interventional
• Enrollment (Estimated): 864
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Chuansheng Zhao, M.D; Phone Number: +86 13940369251; Email: cszhao@mail.cmu.edu.cn
• Study Contact Backup: Name: Jinwei Li, M.D; Phone Number: +86 15804060747; Email: lijinw07@126.com

Study Locations

• China
  • Fujian
    • Fuzhou, Fujian, China, 350001
      • Fujian Medical University Union Hospital
      • Contact: Wenhuo Chen, M.D; Phone Number: +86 13806906089; Email: lijinw07@126.com
  • Liaoning
    • Anshan, Liaoning, China, 114001
      • Anshan Central Hospital
      • Contact: Hongbo Xiao; Phone Number: +86 13942211121
    • Anshan, Liaoning, China, 114005
      • Anshan Changda Hospital
      • Contact: Yulin Song; Phone Number: +86 18941269240
    • Benxi, Liaoning, China, 117000
      • Benxi Central Hospital
      • Contact: Chengguang Song; Phone Number: +86 15141488936
    • Chaoyang, Liaoning, China, 122000
      • Chaoyang Central Hospital
      • Contact: Xiaomei He; Phone Number: +86 18040158900
    • Dalian, Liaoning, China, 116033
      • Dalian Municipal Central Hospital Affiliated of Dalian University of Technology
      • Contact: Di Li; Phone Number: +86 15040593175; Email: lijinw07@126.com
    • Dandong, Liaoning, China, 118000
      • Dandong Central Hospital
      • Contact: Ming Sun; Phone Number: +86 13842590407
    • Dandong, Liaoning, China, 118000
      • Dandong First Hospital
      • Contact: Lishu Wan; Phone Number: +86 18004955099
    • Fushun, Liaoning, China, 113006
      • Fushun Central Hospital
      • Contact: Yan Yang; Phone Number: +86 13941358008
    • Fushun, Liaoning, China, 113008
      • Liaojian Group Fukuang General Hospital
      • Contact: Hong Zhang; Phone Number: +86 13941363522
    • Fuxin, Liaoning, China, 123000
      • Fuxin People's Hospital
      • Contact: Ying Bao; Phone Number: +86 13384189988
    • Huludao, Liaoning, China, 125000
      • Huludao Central Hospital
      • Contact: Changming Xu; Phone Number: +86 15382008866
    • Jinzhou, Liaoning, China, 121001
      • The First Affiliated Hospital of Jinzhou Medical University
      • Contact: Li Liu; Phone Number: +86 13591642556
    • Liaoyang, Liaoning, China, 111000
      • Liaoyang Central Hospital
      • Contact: Xinbin Hao; Phone Number: +86 13841998567
    • Panjin, Liaoning, China, 124010
      • Panjin Central Hospital
      • Contact: Zhuo Li; Phone Number: +86 18942750777
    • Shenyang, Liaoning, China, 110032
      • The fourth Affiliated Hospital of China Medical University
      • Contact: Zhenwei He; Phone Number: +86 18900913396
    • Shenyang, Liaoning, China, 110002
      • The Second Affiliated Hospital of Shenyang Medical College
      • Contact: Yan Du; Phone Number: +86 18002453421
    • Shenyang, Liaoning, China, 110016
      • Liaoning Provincial People's Hospital
      • Contact: Muhui Lin; Phone Number: +86 17702485111
    • Shenyang, Liaoning, China, 110023
      • Shenyang Fifth People's Hospital
      • Contact: Jinchun Wang; Phone Number: +86 13889228138
    • Shenyang, Liaoning, China, 110024
      • Central Hospital Affiliated to Shenyang Medical College
      • Contact: Runhui Li; Phone Number: +86 18002477116
    • Shenyang, Liaoning, China, 110031
      • Shenyang Fourth People's Hospital
    • Shenyang, Liaoning, China, 110041
      • Shenyang First People's Hospital
      • Contact: Li Li; Phone Number: +86 13840247222
    • Shenyang, Liaoning, China, 110044
      • Shenyang Tenth People's Hospital
    • Shenyang, Liaoning, China, 110101
      • Sujiatun District Central Hospital
      • Contact: Hongxia Zhao; Phone Number: +86 13842001757
    • Tieling, Liaoning, China, 112000
      • Tieling Central Hospital
      • Contact: Yong Liang; Phone Number: +86 13941047667
    • Tieling, Liaoning, China, 112600
      • Tieling County Central Hospital
      • Contact: Liying Shen; Phone Number: +86 13804107177
    • Tieling, Liaoning, China, 112700
      • Liaojian Group Tieling Coal General Hospital
      • Contact: Gaohua Li; Phone Number: +86 15694138278
    • Wafangdian, Liaoning, China, 116300
      • Wafangdian Central Hospital
      • Contact: Wei Li; Phone Number: +86 15566896782
    • Wafangdian, Liaoning, China, 116300
      • Wafangdian Third People's Hospital
      • Contact: Renlin Zou; Phone Number: +86 15641120499
    • Yingkou, Liaoning, China, 115000
      • Yingkou Central Hospital
      • Contact: Dongqun Li; Phone Number: +86 13941728080

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tenecteplase; Tenecteplase (0.25 mg/kg, intravenous bolus, maximum dose 25 mg) + Standard Medical Management	Drug: Tenecteplase (0.25mg/kg); Tenecteplase (0.25 mg/kg, intravenous bolus, maximum dose 25 mg) + Delayed dual antiplatelet therapy (initiated 24 hours after thrombolysis: Aspirin 100 mg orally once daily + Clopidogrel 75 mg orally once daily, or Aspirin 100 mg + Ticagrelor 90 mg orally twice daily, continued for 21 days)
Active Comparator: Standard Medical Management; Immediate Standard Medical Management	Drug: Standard Medical Management; Immediate dual antiplatelet therapy (Aspirin 100 mg orally once daily + Clopidogrel 75 mg orally once daily, or Aspirin 100 mg + Ticagrelor 90 mg orally twice daily, continued for 21 days)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients with a modified Rankin Scale (mRS) score of 0-1 at 90 days.	Proportion of patients with a modified Rankin Scale (mRS) score of 0-1 at 90 days.	3 months after randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients with mRS 0-2 at 90 days.	Proportion of patients with mRS 0-2 at 90 days.	3 months after randomization
Distribution of mRS score at 90 days.	Distribution of mRS score at 90 days.	3 months after randomization
Rate of vessel recanalization.	Rate of vessel recanalization.	3 months after randomization
Proportion of patients undergoing rescue mechanical thrombectomy.	Proportion of patients undergoing rescue mechanical thrombectomy.	cerebral infarction within 24 hours of onset
Proportion of patients with NIHSS score 0-1 or an improvement of ≥4 points from baseline at 24 hours, 7 days, or discharge (whichever occurs first).	Proportion of patients with NIHSS score 0-1 or an improvement of ≥4 points from baseline at 24 hours, 7 days, or discharge (whichever occurs first).	24 hours, 7 days, or discharge after randomization
Proportion of patients with neurological deterioration at 90 days (increase in NIHSS score ≥4 points from baseline at the 90-day follow-up).	Proportion of patients with neurological deterioration at 90 days (increase in NIHSS score ≥4 points from baseline at the 90-day follow-up).	3 months after randomization
New vascular events within 90 days (including ischemic stroke, hemorrhagic stroke, myocardial infarction, and vascular death), with independent evaluation of each event.	New vascular events within 90 days (including ischemic stroke, hemorrhagic stroke, myocardial infarction, and vascular death), with independent evaluation of each event.	3 months after randomization

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Increase in NIHSS score ≥4 points within 24 hours, excluding intracranial hemorrhage.	Increase in NIHSS score ≥4 points within 24 hours, excluding intracranial hemorrhage.	24 hours after randomization
Symptomatic intracranial hemorrhage (sICH) at 36 hours (ECASS III definition).	Symptomatic intracranial hemorrhage (sICH) at 36 hours (ECASS III definition).	36 hours after randomization
sICH within 90 days (ECASS III definition).	sICH within 90 days (ECASS III definition).	3 months after randomization
PH2 intracranial hemorrhage within 90 days (Heidelberg criteria: hematoma occupying ≥30% of the infarcted area with significant mass effect).	PH2 intracranial hemorrhage within 90 days (Heidelberg criteria: hematoma occupying ≥30% of the infarcted area with significant mass effect).	3 months after randomization
Any intracranial hemorrhage within 90 days.	Any intracranial hemorrhage within 90 days.	3 months after randomization
Severe bleeding events in other parts of the body within 90 days (GUSTO definition).	Severe bleeding events in other parts of the body within 90 days (GUSTO definition).	3 months after randomization
Death within 90 days.	Death within 90 days.	3 months after randomization
Adverse events/Serious adverse events (AE/SAE) within 90 days.	Adverse events/Serious adverse events (AE/SAE) within 90 days.	3 months after randomization

Collaborators and Investigators

• Sponsor: First Hospital of China Medical University

Study record dates

Study Major Dates

• Study Start (Estimated): March 1, 2026
• Primary Completion (Estimated): July 1, 2028
• Study Completion (Estimated): August 1, 2028

Study Registration Dates

• First Submitted: March 10, 2026
• First Submitted That Met QC Criteria: March 12, 2026
• First Posted (Actual): March 17, 2026

Study Record Updates

• Last Update Posted (Actual): March 17, 2026
• Last Update Submitted That Met QC Criteria: March 12, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Tenecteplase; beyond 4.5 hours; Ischemic Stroke with Large Vessel Occlusion
• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Stroke; Amino Acids, Peptides, and Proteins; Proteins; Hydrolases; Enzymes; Enzymes and Coenzymes; Blood Proteins; Endopeptidases; Peptide Hydrolases; Serine Endopeptidases; Serine Proteases; Plasminogen Activators; Blood Coagulation Factors; Tissue Plasminogen Activator; Tenecteplase
• Other Study ID Numbers: TIME-MINOR-2026

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No