Intra-arterial Thrombolysis For Acute Ischemic Stroke With Medium Vessel Occlusion

NCT07668323 | Recruiting Phase 3 DMC

• 1 other identifier: 2026-SR-399.A1
• Study Type: interventional
• Target: 372
• Locations: 1 country
• Sites: 1

Brief Summary

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. 1.Procedure-related complications within 24 hours post-randomization;
2. 2.Recanalization rate (meTICI ≥ 2b) at 24±12 hours post-randomization;
3. 3.Any intracranial hemorrhage within 48 hours post-randomization;
4. 4.Early neurological improvement (NIHSS score change from baseline) at 7 days or discharge;
5. 5.Overall distribution of mRS scores at 90±7 days (shift analysis);
6. 6.Excellent functional outcome (mRS score 0-1) at 90±7 days;
7. 7.Functional independence (Barthel Index score 95 or 100) at 90±7 days;
8. 8.Health-related quality of life (EQ-5D-5L) at 90±7 days;
9. 9.All-cause mortality within 90±7 days.

Conditions

Medium Vessel Occlusion; Ischemic Stroke, Acute

Keywords

medium vessel occlusion; acute ischemic stroke; intra-arterial thrombolysis

Outcome Measures

Primary Outcomes (3)

• 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.

  90 days post-randomization (90±7 days)

• 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.

  48 hours post-randomization

• 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.

  7 days post-randomization

Secondary Outcomes (9)

• Proportion of patients with procedure-related complications

  Within 24 hours post-randomization

• Recanalization rate at 24 hours

  24±12 hours post-randomization

• Proportion of patients with any intracranial hemorrhage at 48 hours

  48 hours post-randomization

• Early neurological improvement at 7 days

  7 days post-randomization or hospital discharge, whichever occurs first

• Overall distribution of functional outcomes at 90 days

  90±7 days post-randomization

Other Outcomes (1)

• Rescue therapy rate

  Within 24 hours post-randomization

Study Arms (2)

Intra-arterial Thrombolysis plus Best Medical Management

EXPERIMENTAL

Participants receive intra-arterial thrombolysis (IAT) via microcatheter plus best medical management (BMM). For small thrombus, microcatheter is positioned adjacent to or within the thrombus. For larger burden, microcatheter is advanced through the occluded segment with staged administration from distal to proximal portions (one-third of total dose per segment). Agent: alteplase 0.225 mg/kg (max 22.5 mg) or tenecteplase 0.0625 mg/kg (max 6.25 mg), administered over 15-30 min, consistent with any prior IV thrombolysis. Procedure ends at meTICI ≥ 2b or when risks outweigh benefits. BMM includes antiplatelet, anticoagulation (if indicated), statins, BP/glycemic control, and rehabilitation.

Drug: Recombinant Tissue Plasminogen Activator (rt-PA); Procedure: Intra-arterial Thrombolysis; Drug: Best Medical Management; Procedure: Rescue therapy

Best Medical Management Alone

ACTIVE COMPARATOR

Participants receive best medical management alone per local guidelines, including antiplatelet therapy, anticoagulation (if indicated), statins, blood pressure and glycemic control, and rehabilitation. No endovascular intervention is performed as part of the randomized treatment; protocol-specified rescue therapy is the only exception.

Drug: Best Medical Management; Procedure: Rescue therapy

Interventions

Rescue therapy PROCEDURE

Rescue 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.

Best Medical Management Alone; Intra-arterial Thrombolysis plus Best Medical Management

Intra-arterial Thrombolysis PROCEDURE

Microcatheter 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.

Intra-arterial Thrombolysis plus Best Medical Management

Best Medical Management DRUG

Best medical management per local guidelines, including antiplatelet therapy, anticoagulation (if indicated), statins, blood pressure and glycemic control, and rehabilitation.

Best Medical Management Alone; Intra-arterial Thrombolysis plus Best Medical Management

Recombinant Tissue Plasminogen Activator (rt-PA) DRUG

Administered 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.

Also known as: Tenecteplase (TNK)

Intra-arterial Thrombolysis plus Best Medical Management

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• Uncontrolled hypertension refractory to medical therapy (systolic blood pressure \> 220 mmHg or diastolic blood pressure \> 120 mmHg).
• Baseline blood glucose \< 2.8 mmol/L (50 mg/dL) or \> 22.2 mmol/L (400 mg/dL).
• Known bleeding diathesis, including but not limited to: platelet count \< 100 × 10⁹/L; heparin treatment within 48 hours with APTT ≥ 35 seconds; oral warfarin with INR \> 3. Note: Patients without a history or suspicion of coagulation disorders do not require laboratory testing for coagulation parameters prior to enrollment.
• Stroke onset with seizure or seizure occurring during the course of stroke, precluding accurate determination of baseline NIHSS score.
• Female patients who are pregnant, lactating, or have a positive pregnancy test at hospital admission.
• Currently participating in another investigational drug or device study that may interfere with the results of this study.
• Other conditions judged by the investigator to be unsuitable for participation or posing significant risk to the patient.
• Intracranial hemorrhage confirmed by baseline head CT or MRI, including parenchymal hemorrhage, intraventricular hemorrhage, subarachnoid hemorrhage, or subdural/epidural hemorrhage.
• Presence of midline shift or cerebral herniation, or other ventricular mass effect with midline shift.
• Anticipated inability to complete endovascular treatment due to vascular tortuosity, severe vessel wall calcification, or other anatomical challenges.
• Aortic dissection.

Sponsors & Collaborators

• The First Affiliated Hospital with Nanjing Medical University: lead

Study Sites (1)

the First Affiliated Hospital with Nanjing Medical University

Nanjing, Jiangsu, 210000, China

RECRUITING

MeSH Terms

Conditions

Ischemic Stroke

Interventions

Tissue Plasminogen Activator; Tenecteplase

Condition Hierarchy (Ancestors)

Stroke; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Serine Endopeptidases; Endopeptidases; Peptide Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Serine Proteases; Plasminogen Activators; Blood Coagulation Factors; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Biological Factors

Study Officials

• Sheng Liu, Professor

  The First Affiliated Hospital with Nanjing Medical University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Xinglong Liu, Doctor

CONTACT

+8618262638087; plear_new@163.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief Physician

Study Record Dates

• First Submitted: June 22, 2026
• First Posted: June 25, 2026
• Study Start: September 19, 2026
• Primary Completion (Estimated): January 31, 2029
• Study Completion (Estimated): May 31, 2029
• Last Updated: September 23, 2026

Record last verified: 2026-09

Locations

CN (1)