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

Intravenous Thrombolysis With Recombinant Human TNK Tissue-type Plasminogen Activator (rhTNK-tPA) for Acute Non-large Vessel Occlusion in Extended Time Window--A Multicenter, Prospective, Randomized, Open-label, Blinded End-point Trial

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.

Study Overview

• Status: Completed
• Conditions: Acute Ischemic Stroke
• Intervention / Treatment: Drug: rhTNK-tPA; Drug: Antiplatelet Agents

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.

• Study Type: Interventional
• Enrollment (Actual): 570
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Beijing, China
    • Xuanwu Hospital, Capital Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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)

Specific Neuroimaging Exclusion Criteria:

• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: 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).
Active Comparator: 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.	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); Other Names: Aspirin; Clopidogrel

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Excellent functional outcome	Proportion of subjects with mRS 0-1 at 90±7 days	90±7 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
modified Rankin Scale (mRS) score	Ordinal distribution of mRS at 90±7 days; modified Rankin scale (range, 0 to 6, with a score of 0 indicating no disability, 1 no clinically significant disability, 2 slight disability, 3 moderate disability but remaining able to walk unassisted, 4 moderately severe disability, 5 severe disability, and 6 death)	90±7 days
Good functional outcome	Proportion of subjects with mRS 0-2 at 90±7 days	90±7 days
Rate of successful reperfusion	>90% reduction of the Tmax>6s lesion volumes between the baseline and early follow-up at 24 hours (-2/+12 hours)	24 hours (-2/+12 hours)
Early clinical recovery	Proportion of subjects with NIHSS score≥8 improved compared with baseline or with NIHSS 0-1 at 24 hours (-2/+12 hours)	24 hours (-2/+12 hours)
Change of National Institutes of Health Stroke Scale (NIHSS)	Change of NIHSS score from baseline to 7 days (±2days)	7±2 days
Infarct volume at 24 hours (-2/+12 hours)	The infarct volume is determined on evaluated on NCCT at 24 hours (-2/+12 hours)	24 hours (-2/+12 hours)
Functional health status and quality of life	Functional health status and quality of life (EQ-5D-5L) at 90±7 days	90±7 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of clinically significant intracranial hemorrhage	Incidence of sICH (Heidelberg criteria) measured at 36 hours	36 hours
Incidence of major bleeding	Incidence of major bleeding defined as GUSTO severe/life threatening or moderate bleeds measured at 90±7 days	90±7 days
All-cause mortality	All-cause mortality at 90±7 days	90±7 days

Collaborators and Investigators

• Sponsor: Xuanwu Hospital, Beijing
• Collaborators: Beijing Hospitals Authority; CSPC Mingfule Pharmaceutical (Guangzhou) Co., Ltd.
• Investigators: Principal Investigator: Junwei Hao, MD, Xuanwu Hospital, Beijing; Principal Investigator: Qingfeng Ma, MD, Xuanwu Hospital, Beijing

Study record dates

Study Major Dates

• Study Start (Actual): June 2, 2023
• Primary Completion (Actual): October 28, 2025
• Study Completion (Actual): October 28, 2025

Study Registration Dates

• First Submitted: February 9, 2023
• First Submitted That Met QC Criteria: March 1, 2023
• First Posted (Actual): March 3, 2023

Study Record Updates

• Last Update Posted (Actual): December 2, 2025
• Last Update Submitted That Met QC Criteria: December 1, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: acute ischemic stroke; intravenous thrombolysis; extended time window; non-large vessel occlusion
• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Stroke; Ischemic Stroke; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pharmacologic Actions; Chemical Actions and Uses; Therapeutic Uses; Hydrocarbons; Hydrocarbons, Cyclic; Hydrocarbons, Aromatic; Phenols; Benzene Derivatives; Thiophenes; Salicylates; Hydroxybenzoates; Ticlopidine; Thienopyridines; Hematologic Agents; Clopidogrel; Aspirin; Platelet Aggregation Inhibitors
• Other Study ID Numbers: [2022]205

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

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