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

NCT ID: NCT05752916

Last Updated: 2025-12-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 570 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-06-02
• Study Completion Date: 2025-10-28

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.

Detailed Description

OPTION is a multicenter, prospective, randomized, open-label, blinded end-point (PROBE) controlled trial of thrombolysis with rhTNK-tPA versus standard of care. A total of 568 patients will be enrolled at approximately 40 centers around China.

Conditions

Acute Ischemic Stroke

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Intravenous rhTNK-tPA

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.

Group Type: EXPERIMENTAL

rhTNK-tPA

Intervention Type: 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).

Standard Medical Treatment

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.

Group Type: ACTIVE_COMPARATOR

Antiplatelet Agents

Intervention Type: 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)

Interventions

rhTNK-tPA

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).

Intervention Type: DRUG

Antiplatelet Agents

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)

Intervention Type: DRUG

Other Intervention Names

Aspirin; Clopidogrel

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

• 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
• Severe, uncontrolled hypertension (systolic blood pressure >185mmHg or diastolic blood pressure >110mmHg)
• Any terminal illness such that the patient would not be expected to survive more than half a year
• Current participation in any investigational study that may confound outcome assessment of the study
• Any condition that, in the judgement of the investigator, is inappropriate for participation in the trial or could impose hazards to the patient (e.g. inability to understand and/or follow the study procedures and/or follow-up due to mental disorders, cognitive or emotional disorders)

• Evidence of acute intracranial hemorrhage
• Acute large vessel occlusion on magnetic resonance/ computed tomography angiography, including internal carotid artery (ICA), middle cerebral artery M1 segment (MCA-M1）, vertebral artery and basilar artery

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

CSPC Mingfule Pharmaceutical (Guangzhou) Co., Ltd.

INDUSTRY

Sponsor Role: collaborator

Beijing Hospitals Authority

UNKNOWN

Sponsor Role: collaborator

Xuanwu Hospital, Beijing

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Junwei Hao, MD

Role: PRINCIPAL_INVESTIGATOR

Xuanwu Hospital, Beijing

Qingfeng Ma, MD

Role: PRINCIPAL_INVESTIGATOR

Xuanwu Hospital, Beijing

Locations

Xuanwu Hospital, Capital Medical University

Beijing, , China

Countries

China

Other Identifiers

[2022]205

Identifier Type: -

Identifier Source: org_study_id