Intravenous Thrombolysis With rhTNK-tPA for Acute Non-large Vessel Occlusion in Extended Time Window

NCT05752916 | Completed Phase 4 DMC

• 1 other identifier: [2022]205
• Study Type: interventional
• Target: 570
• Locations: 1 country
• Sites: 1

Brief Summary

This study is designed to evaluate the efficacy of IV rhTNK-tPA between 4.5 to 24 hours from symptom onset in patients presenting with a non-large vessel occlusion ischemic stroke.

Conditions

Acute Ischemic Stroke

Keywords

acute ischemic stroke; extended time window; non-large vessel occlusion; intravenous thrombolysis

Outcome Measures

Primary Outcomes (1)

• Excellent functional outcome

  Proportion of subjects with mRS 0-1 at 90±7 days

  90±7 days

Secondary Outcomes (7)

• modified Rankin Scale (mRS) score

  90±7 days

• Good functional outcome

  90±7 days

• Rate of successful reperfusion

  24 hours (-2/+12 hours)

• Infarct volume at 24 hours (-2/+12 hours)

  24 hours (-2/+12 hours)

• Early clinical recovery

  24 hours (-2/+12 hours)

Other Outcomes (3)

• Incidence of clinically significant intracranial hemorrhage

  36 hours

• Incidence of major bleeding

  90±7 days

• All-cause mortality

  90±7 days

Study Arms (2)

Intravenous rhTNK-tPA

EXPERIMENTAL

rhTNK-tPA(0.25mg/kg) given as a single, intravenous bolus immediately upon randomization. Experimental treatment will be administered as a single intravenous bolus over 5-10 seconds as per the standard manufacturers' instructions for use.

Drug: rhTNK-tPA

Standard Medical Treatment

ACTIVE COMPARATOR

Antiplatelet therapy (aspirin or clopidogrel alone) at the discretion of local investigators according to Chinese Guidelines for Diagnosis and Treatment of Acute Ischemic Stroke 2023.

Drug: Antiplatelet Agents

Interventions

rhTNK-tPA DRUG

Recombinant human TNK tissue-type plasminogen activator. Patients will receive intravenous rhTNK-tPA (0.25mg/kg, maximum 25mg, administered as a bolus over 5-10 seconds).

Intravenous rhTNK-tPA

Antiplatelet Agents DRUG

Aspirin (150-300mg) is offered to patients allocated in the control arm, unless contraindicated. According to Chinese Guidelines for Diagnosis and Treatment of Acute Ischemic Stroke 2023, 150-300mg aspirin alone is recommended for acute stroke treatment in patients who are otherwise eligible for intravenous thrombolysis or EVT as soon as possible (Class 1 of recommendation, Level A of evidence). The aspirin dose can be changed to 50-300 mg/day after the acute phase. Clopidogrel is indicated as an alternative in case of aspirin intolerance (Class 2 of recommendation, Level C of evidence)

Also known as: Aspirin, Clopidogrel

Standard Medical Treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Clinical diagnosis of acute ischemic stroke
• Age≥18 years
• Pre-stroke mRS score≤1 points
• Disabling stroke defined as follows:
• Baseline NIHSS score 6-25 at the time of randomization,
• Or NIHSS 4-5 with disabling deficit (e.g. hemianopia, aphasia, loss of hand function) as determined by the managing clinician
• Onset (last-seen-well) time to treatment time between 4.5 and 24 hours
• Written informed consent from patients or legally responsible representatives
• The presence of a Target Mismatch on CT perfusion: ischemic core volume\<50ml (defined as rCBF\<30%), mismatch ratio≥1.2 (Tmax\>6 sec lesion/core volume lesion), mismatch volume≥10ml

You may not qualify if:

• Treatment with a thrombolytic within the last 72 hours or intention to receive intravenous thrombolysis
• Contraindication to thrombolysis
• Planned or anticipated treatment with endovascular therapy
• Rapidly improving symptoms, particularly if in the judgment of the managing clinician that the improvement is likely to result in a NIHSS score\<4 at randomization
• Pregnancy or lactating; formal testing needed in women of childbearing potential
• Brain tumor (with mass effect)
• Hereditary or acquired hemorrhagic diathesis, coagulation factor deficiency
• Impairment in coagulation due to comorbid disease or anticoagulant use. If on warfarin, international normalized ratio (INR) \>1.7 or prothrombin time \>15s; if use of any direct oral anticoagulant within the last 48 hours; if use of heparin/heparinoid within the last 24 hours
• Use of glycoprotein Ⅱb-Ⅲa inhibitors within the last 72 hours
• Baseline platelet count \<100,000/μL
• Undergoing hemodialysis or peritoneal dialysis; known severe renal insufficiency with glomerular filtration rate \<30ml/min or serum creatinine \>220mmol/L (2.5mg/dl)
• Suspected aortic dissection
• Major surgery or biopsy within the last 1 month
• Any active bleeding within the previous 1 month (including gastrointestinal or urinary bleeding)
• Known severe, life-threatening allergy (more severe than skin rash) to contrast agents

Sponsors & Collaborators

• Xuanwu Hospital, Beijing: lead
• CSPC Mingfule Pharmaceutical (Guangzhou) Co., Ltd.: collaborator
• Beijing Hospitals Authority: collaborator

Study Sites (1)

Xuanwu Hospital, Capital Medical University

Beijing, China

Location

MeSH Terms

Conditions

Ischemic Stroke

Interventions

Platelet Aggregation Inhibitors; Aspirin; Clopidogrel

Condition Hierarchy (Ancestors)

Stroke; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Hematologic Agents; Therapeutic Uses; Pharmacologic Actions; Chemical Actions and Uses; Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Ticlopidine; Thienopyridines; Thiophenes; Sulfur Compounds; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Junwei Hao, MD

  Xuanwu Hospital, Beijing

  PRINCIPAL INVESTIGATOR

• Qingfeng Ma, MD

  Xuanwu Hospital, Beijing

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: An imaging core laboratory (ICL) is to provide an unbiased assessment of imaging measures. They are knowledgeable in the analysis of neuroradiological images and will be blinded, i.e. unaware of the patient's treatment allocation and trial outcome.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: prospective, randomized, open label, blinded-endpoint (PROBE)

Study Record Dates

• First Submitted: February 9, 2023
• First Posted: March 3, 2023
• Study Start: June 2, 2023
• Primary Completion: October 28, 2025
• Study Completion: October 28, 2025
• Last Updated: December 2, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)