Stroke, Acute Ischemic
Conditions
Brief summary
A multicenter, prospective, open-label, blinded endpoint, randomized controlled trial aiming at evaluating the efficacy and safety of intra-arterial recombinant human tissue plasminogen activator (rt-PA) after successful recanalization of acute large vessel occlusion in the anterior circulation by mechanical thrombectomy in improving the 90-day functional outcome.
Detailed description
This study is a multicenter, prospective, open-label, blinded endpoint, randomized controlled trial designed to evaluate the efficacy and safety of intra-arterial recombinant human tissue plasminogen activator (rt-PA) after successful recanalization of acute large vessel occlusion in the anterior circulation by mechanical thrombectomy (eTICI 2b50/3). The primary outcome is the proportion of patients with a 90-day modified Rankin scale (mRS) of 0-1. Study intervention: (1) Participants in the experimental group will receive intra-arterial alteplase (a dose of 0.225 mg/kg and a maximum dose of 20 mg) after the mechanical thrombectomy, and will receive standard medical treatment after the procedure. (2) Participants in the control group will receive standard medical treatment without intra-arterial alteplase. A total of 324 participants are anticipated to be recruited for this study, with 162 participants in each group (1:1 ratio).
Interventions
DRUGAlteplase
See arm/group descriptions.
Sponsors
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
Shenzhen Hospital of Southern Medical University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Aged 18 years or older. 2. Clinical diagnosis of acute ischemic stroke. 3. Time from symptom onset to randomization within 24 hours, including wake-up stroke or no-witness stroke; the onset time refers to "Last Known Well" (LKW). 4. CTA or MRA confirmed occlusion of the intracranial segment of the internal carotid artery, or M1 or M2 segment of the middle cerebral artery; stable eTICI score of 2b50-3 after mechanical thrombectomy, with or without intravenous thrombolysis. Patients with an eTICI score of 2b50-3 on the diagnostic cerebral angiography before mechanical thrombectomy are also eligible for the study. 5. Baseline NIHSS of 6-25. 6. NCCT/DWI-MRI ASPECTS ≥ 6; 7. Pre-stroke mRS score ≤ 1, or mRS \>1 but not related to neurological disease (e.g., amputation, blindness). 8. Signed informed consent.
Exclusion criteria
1. Contraindication to rt-PA (except time to therapy). 2. Planned use of dual antiplatelet therapy within the first 24 hours after mechanical thrombectomy. 3. Angiographic evaluation showing dissection, severe stenosis, or complete occlusion of the carotid artery, which requires the use of carotid artery stents during the endovascular procedure. 4. Suspected cerebral vasculitis based on medical history and/or angiographic evaluation. 5. Women who are pregnant or breastfeeding. 6. Participation in other clinical trials. 7. Preoperative intracranial hemorrhage confirmed by cranial CT or MRI. 8. Known genetic or acquired bleeding disposition with anticoagulation factor deficiency. 9. Coagulation disorder with INR \> 1.7 or use of new oral anticoagulants (within 48 hours of symptom onset). 10. Platelet count \<50X10\^9/L. 11. Suspected vascular occlusion as a result of infective endocarditis. 12. Known severe renal insufficiency with glomerular filtration rate \<30 ml/min or blood creatinine \>220 μmol/L (2.5 mg/dl). 13. Severe allergy to contrast (non-mild rash allergy) or absolute contraindication to iodine contrast. 14. Suspected aortic dissection. 15. Previous parenchymal organ surgery or biopsy in the last 1 month; 16. Any active bleeding or recent bleeding (gastrointestinal, urinary tract bleeding, etc.) in the last 1 month; 17. SBP \> 185 mmHg or DBP \> 110 mmHg refractory to treatment. 18. Anticipated life expectancy \< 6 months (e.g., malignancy, severe cardiopulmonary disease, etc.). 19. Any condition that, in the judgment of the investigator, makes the patient unsuitable for this study or where this study may impose a significant risk to the patient (e.g., inability to understand and/or comply with study procedures and/or follow-up due to psychiatric disorders, cognitive or emotional impairment).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The modified Rankin Scale score (mRS) 0-1 | 90(±7) days | The proportion of the modified Rankin Scale score (mRS) 0-1 at 90 days. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change of infarct volume from baseline | 7(±1) days | The change of infarct volume at 7(±1) days or discharge (whichever occurred first) on non-contrast CT, or at 48(±12) hours on MRI |
| The volume of Tmax>6s on CTP | 24(±12) hours | The volume of Tmax\>6s on CTP at 24(±12) hours |
| The shift analysis of the modified Rankin Scale (mRS) | 90(±7) days | The shift analysis of the modified Rankin Scale (mRS) at 90 days |
| The modified Rankin Scale score (mRS) 0-2 | 90(±7) days | The proportion of the modified Rankin Scale score (mRS) 0-2 at 90 days. |
| The modified Rankin Scale score (mRS) 0-3 | 90(±7) days | The proportion of the modified Rankin Scale score (mRS) 0-3 at 90 days. |
| The proportion of NIHSS 0-1 or ≥10 points reduction | 48 (±12) hours | The proportion of NIHSS 0-1 or ≥10 points reduction at 48 (±12) hours |
| Quality of Life (EQ-5D-5L) | 90(±7) days | The value of Quality of Life (EQ-5D-5L) at 90 days |
Countries
China
Contacts
PRINCIPAL_INVESTIGATORYamei Tang
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
PRINCIPAL_INVESTIGATORYajie Liu
Shenzhen Hospital of Southern Medical University
Outcome results
None listed