Intra-arterial Thrombolysis For Acute Ischemic Stroke With Medium Vessel Occlusion
Trial statusRecruiting
Trial phasePhase 3
Trial typeInterventional
Biological sexAll
Age18-80
SponsorThe First Affiliated Hospital with Nanjing Medical University
About this 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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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.
Disqualifiers
Pre-stroke modified Rankin Scale (mRS) score > 2.
Presence of contraindications to intravenous thrombolysis.
Known allergy to heparin, contrast media, anesthetics, or other definite contraindications to endovascular treatment.
Comorbid severe diseases that may affect outcome assessment, including but not limited to malignancy, severe heart failure, or renal failure, with expected life expectancy < 6 months.
Trial design
Design model
Parallel
Treatments tested in this trial
Recombinant Tissue Plasminogen Activator (rt-PA)
DrugAdministered intra-arterially via microcatheter. Agent options: alteplase (rt-PA) at 0.225 mg/kg (maximum 22.5 mg) or tenecteplase (TNK) at 0.0625 mg/kg (maximum 6.25 mg), infused over 15-30 minutes. The choice of agent should be consistent with any prior intravenous thrombolysis.
Intra-arterial Thrombolysis
Procedure/SurgeryMicrocatheter is navigated to the occluded medium vessel. For small thrombus burden, positioned adjacent to or within the thrombus. For larger burden, advanced through occluded segment with staged administration distal-to-proximal (one-third per segment). Procedure ends at meTICI ≥ 2b or when risks outweigh benefits.
Best Medical Management
DrugBest medical management per local guidelines, including antiplatelet therapy, anticoagulation (if indicated), statins, blood pressure and glycemic control, and rehabilitation.
Rescue therapy
Procedure/SurgeryRescue intra-arterial thrombolysis is permitted in both treatment groups, including participants randomized to best medical management alone, if neurological deterioration occurs after randomization, defined as an increase of ≥ 4 points in the NIHSS score from baseline after exclusion of non-stroke causes such as hypoglycemia, infection, or metabolic derangement, with imaging evidence of salvageable brain tissue (Tmax \> 6 s volume ≥ 10 mL and core infarct volume \[rCBF \< 30%\] \< 50% of the Tmax \> 6 s volume), and provided that rescue therapy can be initiated within 24 hours of symptom onset or last known well. Rescue endovascular therapy is limited to intra-arterial thrombolysis and administered with same agents (alteplase or tenecteplase) at the same doses specified for the intra-arterial thrombolysis intervention; thrombectomy devices, balloon angioplasty, and stenting are not permitted.
Treatment groups
372 Participants
are divided into 2 treatment groupsGroup A: Intra-arterial Thrombolysis plus Best Medical ManagementExperimental treatment 4 interventions
Group B: Best Medical Management AloneActive comparator 2 interventions
Trial outcomes
Primary outcomes
1
Proportion of patients with favorable functional outcome at 90 days
Favorable functional outcome is defined as a modified Rankin Scale (mRS) score of 0 to 2, assessed at 90±7 days post-randomization. The mRS is a 7-point ordinal scale (range 0-6) measuring functional independence and disability, with 0 indicating no symptoms and 6 indicating death.
Time frame
90 days post-randomization (90±7 days)2
Proportion of patients with symptomatic intracranial hemorrhage at 48 hours
Symptomatic intracranial hemorrhage (sICH) within 48 hours post-randomization, defined according to the Heidelberg Bleeding Classification.
Time frame
48 hours post-randomization3
Proportion of patients with early neurological deterioration at 7 days
Proportion of patients with early neurological deterioration (END) within 7 days post-randomization, defined as an increase of ≥ 4 points in total NIHSS score from baseline, or an increase of ≥ 2 points in any single NIHSS item.
Time frame
7 days post-randomizationSecondary outcomes
1
Proportion of patients with procedure-related complications
Proportion of patients experiencing procedure-related complications associated with intra-arterial intervention, including but not limited to vessel perforation, dissection, distal embolization, and vasospasm.
Time frame
Within 24 hours post-randomization2
Recanalization rate at 24 hours
Proportion of patients achieving successful recanalization, defined as meTICI (modified expanded Thrombolysis in Cerebral Infarction) grade ≥ 2b, assessed at 24±12 hours post-randomization by CTA or MRA.
Time frame
24±12 hours post-randomization3
Proportion of patients with any intracranial hemorrhage at 48 hours
Proportion of patients with any type of intracranial hemorrhage occurring within 48 hours post-randomization, including site and type classified according to the Heidelberg Bleeding Classification.
Time frame
48 hours post-randomization4
Early neurological improvement at 7 days
Change in National Institutes of Health Stroke Scale (NIHSS) score from baseline to 7 days post-randomization or at hospital discharge, whichever occurs first.
Time frame
7 days post-randomization or hospital discharge, whichever occurs firstOther outcomes
1
Rescue therapy rate
Proportion of participants who receive rescue intra-arterial thrombolysis after randomization for neurological deterioration defined as an increase of ≥ 4 points in the NIHSS score from baseline (after exclusion of non-stroke causes such as hypoglycemia, infection, or metabolic derangement), with imaging evidence of salvageable brain tissue (Tmax \> 6 s volume ≥ 10 mL and core infarct volume \[rCBF \< 30%\] \< 50% of the Tmax \> 6 s volume), and provided that rescue therapy is initiated within 24 hours of symptom onset or last known well. Rescue endovascular therapy is limited to intra-arterial thrombolysis; thrombectomy devices, balloon angioplasty, and stenting are not permitted.
Time frame
Within 24 hours post-randomizationSponsors and contacts
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Source ClinicalTrials.gov