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

Detailed Description

OPTION is a multicenter, prospective, randomized, open label, blinded-endpoint (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 (Estimated): 568
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Junwei Hao, MD; Phone Number: 01083198277; Email: haojunwei@vip.163.com
• Study Contact Backup: Name: Gaoting Ma, MD; Phone Number: 18301579891; Email: demo_doctor@163.com

Study Locations

• China
  • Beijing, China
    • Recruiting
    • Xuanwu Hospital, Capital Medical University
    • Contact: Gaoting Ma; Phone Number: 18301579891; Email: demo_doctor@163.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• The clinical diagnosis is acute ischemic stroke (the criteria followed the Chinese Guidelines for the Diagnosis and Treatment of Acute Ischemic Stroke 2018).
• Age≥18 years
• Pre-stroke mRS score≤1 points
• Baseline NIHSS 4-25 (both included) at the time of randomization
• Onset (last-seen-well) time to treatment time between 4.5 and 24 hours
• Informed consent from the patient or surrogate
• 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:

• Treated with intravenous thrombolysis within 72 hours
• Have a clear contraindication for intravenous thrombolysis
• Intended to proceed endovascular treatment
• 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
• Woman of childbearing potential who is known to be pregnant or who has a positive pregnancy test on admission
• Brain tumor (with mass effect)
• Known hereditary or acquired hemorrhagic diathesis, coagulation factor deficiency
• Coagulation Disorders caused by diseases or anticoagulants: warfarin was used with International Normalized Ratio (INR)>1.7 or PT>15s; heparin was administered within 24 hours; novel oral anticoagulants were used within 48 hours
• Glycoprotein IIb-IIIa inhibitors were used within the past 72 hours
• Baseline platelet count <100×109/L
• Known severe renal insufficiency with eGFR<30ml/min or serum creatinine>2.5mg/dl
• Undergoing hemodialysis or peritoneal dialysis; known severe intolerance to contrast media
• Suspected aortic dissection
• Parenchymal organ surgery or biopsy within the previous 1 month
• Any active bleeding within the previous 1 month (including gastrointestinal or urinary bleeding)
• Known severe allergy (more than a rash) to contrast media uncontrolled by medications
• Refractory hypertension (defined as persistent systolic blood pressure>185mmHg or diastolic blood pressure>110mmHg)
• Expected survival time<0.5 year (such as complicated with malignant tumor, serious heart and lung diseases, etc.)
• Participants in other interventional randomized trials that may confound the outcome assessment
• Other circumstances that the investigator considers inappropriate for participation in the trial or that may pose significant risks to patients (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
• Presence of proximal arterial occlusion on CTA/MRA (e.g., intracranial ICA, MCA-M1 and dominant M2 segments, and vertebrobasilar arteries)
• Ischemic core volume>1/3 of the MCA territory defined on CT/MRI

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: Antiplatelet agents; Patients will be treated with standard guideline-directed antiplatelet treatment-choice at the discretion of the clinician. Aspirin will be the choice of most physicians; some will choose to use the clopidogrel. Standard of care medication(s) should be given immediately upon randomization.	Drug: Antiplatelet Agents; Patients will receive single antiplatelet therapy-choice at the discretion of the clinician. Aspirin will be the choice of most physicians, some will choose clopidogrel.; 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)
Change of infarct volume from baseline to 24 hours (-2/+12 hours)	The infarct volume is determined on evaluated on CT 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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of any intracranial hemorrhage	Incidence of any intracranial hemorrhage (Heidelberg criteria) measured at 36 hours	36 hours
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: Guangzhou Recomgen Biotech 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 (Estimated): June 30, 2024
• Study Completion (Estimated): December 30, 2024

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): August 14, 2023
• Last Update Submitted That Met QC Criteria: August 9, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: acute ischemic stroke; intravenous thrombolysis; extended time window; non-large vessel occlusion
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Stroke; Ischemic Stroke; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Clopidogrel; 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