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

Acute Ischemic Stroke Clinical Trial

— OPTION  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05752916
• Other study ID #: [2022]205
• Status: Recruiting
• Phase: Phase 4
• Start date: June 2, 2023
• Est. completion date: December 30, 2024

Study information

• Verified date: March 2023
• Source: Xuanwu Hospital, Beijing
• Contact: Junwei Hao, MD
• Phone: 01083198277
• Email: haojunwei[@]vip.163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 568
• Est. completion date: December 30, 2024
• Est. primary completion date: June 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acute Ischemic Stroke
• Ischemic Stroke

Intervention

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).
• 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.

Locations

Country	Name	City	State
China	Xuanwu Hospital, Capital Medical University	Beijing

Sponsors (2)

Lead Sponsor	Collaborator
Xuanwu Hospital, Beijing	Guangzhou Recomgen Biotech Co., Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Incidence of any intracranial hemorrhage	Incidence of any intracranial hemorrhage (Heidelberg criteria) measured at 36 hours	36 hours
Other	Incidence of clinically significant intracranial hemorrhage	Incidence of sICH (Heidelberg criteria) measured at 36 hours	36 hours
Other	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
Other	All-cause mortality	All-cause mortality at 90±7 days	90±7 days
Primary	Excellent functional outcome	Proportion of subjects with mRS 0-1 at 90±7 days	90±7 days
Secondary	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
Secondary	Good functional outcome	Proportion of subjects with mRS 0-2 at 90±7 days	90±7 days
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	Change of National Institutes of Health Stroke Scale (NIHSS)	Change of NIHSS score from baseline to 7 days (±2days)	7±2 days