Intra-arterial Thrombolysis for Acute Ischemic Stroke With Medium Vessel Occlusion: A Multicenter Prospective Randomized Controlled Clinical Trial
A multicenter, prospective, randomized, open-label, blinded-endpoint (PROBE) phase III trial is planned to evaluate the efficacy and safety of intra-arterial thrombolysis (IAT) in patients with acute ischemic stroke caused by medium vessel occlusion (MeVO, distal M2 \[above the mid-insular height\], M3 or M4; A2, A3 or A4; or P2 or P3 segments, confirmed by CTA or MRA), compared with best medical management alone. Eligible participants (aged 18-80 years, baseline NIHSS score 6-25, confirmed MeVO within 24 hours of symptom onset or last known well) will be randomly assigned 1:1 to the intra-arterial thrombolysis plus best medical management group or the best medical management alone group. The primary endpoints are (i) the proportion of patients with a favorable functional outcome, defined as a modified Rankin Scale (mRS) score of 0-2 at 90±7 days post-randomization; (ii) the proportion of patients with symptomatic intracranial hemorrhage (sICH) within 48 hours post-randomization, defined and classified according to the Heidelberg Bleeding Classification; and (iii) the proportion of patients with early neurological deterioration (END) within 7 days post-randomization, defined as an increase of ≥ 4 points in the total NIHSS score from baseline or an increase of ≥ 2 points in any single NIHSS item. Secondary endpoints: 1. Procedure-related complications within 24 hours post-randomization; 2. Recanalization rate (meTICI ≥ 2b) at 24±12 hours post-randomization; 3. Any intracranial hemorrhage within 48 hours post-randomization; 4. Early neurological improvement (NIHSS score change from baseline) at 7 days or discharge; 5. Overall distribution of mRS scores at 90±7 days (shift analysis); 6. Excellent functional outcome (mRS score 0-1) at 90±7 days; 7. Functional independence (Barthel Index score 95 or 100) at 90±7 days; 8. Health-related quality of life (EQ-5D-5L) at 90±7 days; 9. All-cause mortality within 90±7 days.
• Age 18 to 80 years.
• Time from symptom onset or last known well to randomization within 24 hours.
• Clinical diagnosis of acute ischemic stroke confirmed by CTA or MRA as being caused by isolated acute medium vessel occlusion, including distal M2/M3/M4 segments of the middle cerebral artery, A2/A3/A4 segments of the anterior cerebral artery, or P2/P3 segments of the posterior cerebral artery. Isolated occlusion is defined as a single symptomatic vessel occlusion; patients with multiple vessel occlusions or uncertain culprit vessel are excluded.
• Baseline NIHSS score ≥ 6, and NIHSS score ≤ 25 at the time of randomization.
• For patients presenting beyond 6 hours from symptom onset: perfusion imaging criteria require a Tmax \> 6 s volume ≥ 10 mL and a core infarct volume (defined as rCBF \< 30%) \< 50% of the Tmax \> 6 s volume.
• Patient or legally authorized representative is able to understand and voluntarily sign the informed consent form.