Ischemic Stroke, Medium Vessel Occlusion, Tenecteplase, Endovascular Treatment
Conditions
Brief summary
The ANGEL-MeVO-TNK is a multicentered, prospective, randomized, open label, blinded endpoint (PROBE) phase III trial. A total of 488 AIS patients (age ≥18 years) with acute MeVO-AIS (occlusion of the M2/M3, the A1/A2/A3, the P1/P2/P3, and with baseline NIHSS score \>5 or disabling stroke with NIHSS score 3-5 \[such as neurological deficits in motor strength, language, vision, etc\]), will be enrolled. Patients fulfilling all the inclusion criteria and none of the exclusion criteria will be randomized 1:1 into the IA TNK group or the control group after offering informed content. * The IA TNK group will receive IA TNK (0.2-0.3 mg/min, for 15 -30min), be infused slowly. * The control group will be given standard medical management. The study consists of four visits including the day of randomization, 48±12 hours after randomization, and 90±7 days after randomization. Demographic information, symptoms and signs, laboratory test, neuro-imaging assessment neurological function rating scale will be recorded during the program. The primary outcome is the modified Rankin Scale (mRS) score of 0 to 1 at 90±7 days after onset. The primary safety outcome is the incidence of sICH within 48±12 hours after randomization (ECASS III).
Interventions
Patients will receive standard medical management as recommended by current guidelines# #《Chinese Guidelines for the Diagnosis and Treatment of Acute Ischemic Stroke (2023)》and《Chinese Guidelines for Secondary Prevention of Ischemic Stroke and Transient Ischemic Attack (2022)》
PROCEDUREIntra-arterial Tenecteplase
1. If the patient has not received IVT, IA TNK will be administered as a slow, continuous infusion at a rate of 0.2-0.3 mg/min for super-selective contact thrombolysis, with a duration of 15-30 minutes. A repeat angiogram will be performed 15 minutes after the start of infusion to assess vessel recanalization, and the operator may decide whether to continue drug administration based on the angiographic findings. 2. If the patient has received IVT, intra-arterial TNK will be administered as a slow infusion at a rate of 0.2-0.3 mg/min for super-selective contact thrombolysis, with a duration of 15 minutes. For patients with a body weight \>80 kg, the infusion rate will be limited to 0.2 mg/min for 15 minutes.
Sponsors
Beijing Tiantan Hospital
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Masking description
Since the experimental group needs to perform arterial thrombolysis and related operations on patients, the doctors and nurses involved in the study will not be blinded for random patient allocation. However, the grouping of patients will blind neurologists and nurses responsible for conducting neurological, imaging and functional evaluations at baseline and follow-up, as well as collecting clinical outcome data. The randomization information of the patients will also blind the members of the outcome assessment committee.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Clinical Inclusion Criteria: 1. Age ≥18 years; 2. Pre-stroke mRS 0-1; 3. Within 24 h from symptom onset; 4. Baseline National Institutes of Health Stroke Scale (NIHSS) score \>5 or baseline NIHSS 3-5 with disabling deficit (e.g., loss of hand function, aphasia, hemianopia); 5. Informed consent obtained from patients or their legal representatives. Imaging Inclusion Criteria: 1. Baseline CTA/MRA/DSA diagnosed isolated MeVO, referring to the M2/M3 segment of the MCA, the A1/A2/A3 segment of the ACA, the P1/P2/P3 segment of the PCA; 2. NCCT or MRI DWI imaging showing that the territory of the ischemic infarct volume is less than 50% of the estimated territory supplied by the occluded artery.
Exclusion criteria
1. Acute intracranial hemorrhage; 2. ASPECT ≤5; 3. MeVO secondary to spontaneous fragmentation and distal migration of thrombus from an acute large vessel occlusion, or occurring after intravenous thrombolysis (IVT), intra-arterial thrombolysis, or endovascular thrombectomy; 4. Contraindication to TNK; 5. Known severe allergy to contrast agents (excluding mild rash-type allergic reactions); 6. Use of heparin or novel oral anticoagulants within the previous 48 hours with an INR ≥ 1.7; 7. A history of major bleeding within the past 6 months or the presence of conditions such as active gastrointestinal ulcer, aortic dissection, platelet count \< 100 × 10⁹/L, etc.; 8. Radiologically confirmed vascular malformations, arterial dissection, intracranial aneurysm (diameter≥3 mm), tumors (except small meningiomas), cerebral vasculitis, cerebral amyloid angiopathy, or other major non-ischemic intracranial diseases (e.g., multiple sclerosis); 9. Acute renal failure, current dialysis, or estimated glomerular filtration rate (eGFR)\<30ml/min/1.72m2, and/or serum creatinine\>220mmol/L (2.5mg/dl); 10. History of severe liver disease, or aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) and/or glutamyl transferase (GGT) ≥3×upper limit of normal value (ULN) and/or total bilirubin (TBIL) ≥2×ULN; 11. Severe non-cardiovascular comorbidity with an expected life expectancy of less than 3 months (e.g., malignant tumors); 12. Known pregnancy or breastfeeding, or a positive pregnancy test prior to randomization; 13. Current participation in another drug or device clinical trial; 14. Any other condition deemed by the investigator to make the patient unsuitable for participation in the study or to pose a significant risk to the patient (e.g., inability to understand and/or comply with study procedures and/or follow-up due to psychiatric illness, cognitive impairment, or emotional disorders).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| symptomatic intracerebral hemorrhage within 48±12 hours after randomization | 48±12 hours after randomization | symptomatic intracerebral hemorrhage (sICH) within 48±12 hours after randomization (ECASS III criteria) |
| mRS score of 0 to 1 at 90±7 days after onset | 90±7 days after onset | The modified Rankin scale is a measure of disability, with scores ranging from 0 (no symptoms) to 6 (death), with 0 indicating no symptoms at all; 1 indicating no significant disability despite symptoms: able to carry out all usual duties and activities, 2 indicating slight disability: unable to carry out all previous activities but able to look after own affairs without assistance; 3 indicating moderate disability: requiring some help, but able to walk without assistance; 4 indicating moderately severe disability: unable to walk without assistance, and unable to attend to own bodily needs without assistance; 5 indicating severe disability: bedridden, incontinent, and requiring constant nursing care and attention; and 6 indicating death. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Ordinal mRS score at 90±7 days after onset | 90±7 days after onset | The modified Rankin scale is a measure of disability, with scores ranging from 0 (no symptoms) to 6 (death), with 0 indicating no symptoms at all; 1 indicating no significant disability despite symptoms: able to carry out all usual duties and activities, 2 indicating slight disability: unable to carry out all previous activities but able to look after own affairs without assistance; 3 indicating moderate disability: requiring some help, but able to walk without assistance; 4 indicating moderately severe disability: unable to walk without assistance, and unable to attend to own bodily needs without assistance; 5 indicating severe disability: bedridden, incontinent, and requiring constant nursing care and attention; and 6 indicating death. |
| mRS score 0 to 2 at 90±7 days after onset | 90±7 days after onset | The modified Rankin scale is a measure of disability, with scores ranging from 0 (no symptoms) to 6 (death), with 0 indicating no symptoms at all; 1 indicating no significant disability despite symptoms: able to carry out all usual duties and activities, 2 indicating slight disability: unable to carry out all previous activities but able to look after own affairs without assistance; 3 indicating moderate disability: requiring some help, but able to walk without assistance; 4 indicating moderately severe disability: unable to walk without assistance, and unable to attend to own bodily needs without assistance; 5 indicating severe disability: bedridden, incontinent, and requiring constant nursing care and attention; and 6 indicating death. |
| mRS score 0 to 3 at 90±7 days after onset | 90±7 days after onset | The modified Rankin scale is a measure of disability, with scores ranging from 0 (no symptoms) to 6 (death), with 0 indicating no symptoms at all; 1 indicating no significant disability despite symptoms: able to carry out all usual duties and activities, 2 indicating slight disability: unable to carry out all previous activities but able to look after own affairs without assistance; 3 indicating moderate disability: requiring some help, but able to walk without assistance; 4 indicating moderately severe disability: unable to walk without assistance, and unable to attend to own bodily needs without assistance; 5 indicating severe disability: bedridden, incontinent, and requiring constant nursing care and attention; and 6 indicating death. |
| Number of Participants with Recanalization of the target occluded artery within 48 ± 12 hours after randomization | 48 ± 12 hours after randomization | defined as an Arterial Occlusive Lesion \[AOL\] score of 2-3 on CTA or MRA. The Arterial Occlusive Lesion (AOL) Score is a standardized, angiographic (imaging-based) classification system used to quantify the degree of recanalization (blood flow restoration) in an occluded artery following an endovascular thrombectomy procedure for acute ischemic stroke. Score Range: 0 to 3 (ordinal). A higher score indicates a greater degree of successful mechanical recanalization of the target artery. |
| Infarct volume at 48 ± 12 hours after randomization | 48 ± 12 hours after randomization | Infarct volume at 48 ± 12 hours after randomization (assessed by NCCT or MRI DWI) |
| Change in NIHSS between baseline and 24±2 hours after randomization | 24±2 hours after randomization | The National Institutes of Health Stroke Scale (NIHSS) is a standardized, quantitative assessment tool used by healthcare providers to objectively evaluate and quantify the neurological deficit and severity of impairment in patients with acute ischemic stroke. Total Score Range: 0 to 42. A higher total score indicates greater neurological impairment. |
| Number of Participants with Any ICH within 48±12 hours after randomization | 48±12 hours after randomization | Any ICH within 48±12 hours after randomization |
| Mortality within 90±7 days after onset | 90±7 days after onset | Mortality within 90±7 days after onset |
Countries
China
Contacts
CONTACTLiping Liu
Outcome results
None listed