Intra-arterial tenecteplase for medium-vessel occlusion stroke

Intra-arterial Recombinant Human Tenecteplase Tissue-type Plasminogen Activator (rhTNK-tPA) Thrombolysis for Acute Medium Vessel Occlusion -- A Multicenter, Prospective, Randomized, Open-label, Blinded End-point Trial

This trial will test whether delivering tenecteplase directly into the blocked medium brain artery helps adults with medium-vessel ischemic stroke recover better when treated within 24 hours of symptom onset.

Quick facts

• Phase: PHASE2; PHASE3
• Study type: Interventional
• Enrollment: 382 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Tongji Hospital (other)
• Locations: 1 site (Wuhan, Hubei)
• Trial ID: NCT07302854 on ClinicalTrials.gov

What this trial studies

This is an investigator-initiated, prospective, randomized, open-label, blinded-endpoint (PROBE) phase 2/3 trial planning to enroll 382 patients with confirmed medium-vessel occlusion within 24 hours. Participants are randomized 1:1 to receive intra-arterial recombinant human tenecteplase (rhTNK-tPA) at 0.125 mg/kg (max 12.5 mg) plus standard medical therapy versus standard medical therapy alone. The primary outcome is the proportion of patients achieving a modified Rankin Scale score of 0–1 at 90 days; key eligibility includes age ≥18, pre-stroke mRS 0–1, NIHSS ≥4 or clearly disabling symptoms, and MeVO confirmed by CTA or MRA with imaging criteria for later time windows. The approach tests whether localized, high-concentration thrombolysis can provide reperfusion with less mechanical manipulation and an acceptable safety profile for medium and distal vessel occlusions.

Who should consider this trial

Good fit: Adults (≥18) with pre-stroke mRS 0–1, acute ischemic stroke due to isolated medium/distal vessel occlusion confirmed by CTA/MRA, NIHSS ≥4 or clearly disabling symptoms, presenting within 24 hours (with specific imaging selection for the 6–24 hour window) are ideal candidates.

Not a fit: Patients with large ischemic core volumes, pre-existing significant disability, proximal large-vessel occlusions, active bleeding or contraindications to thrombolysis, or those presenting beyond the allowed time/imaging windows are unlikely to benefit from this approach.

Why it matters

Potential benefit: If successful, this approach could increase the chance of independent function at 90 days for patients with medium-vessel occlusion while avoiding the risks of more invasive procedures.

How similar studies have performed: Recent randomized EVT trials for MeVO (DISTAL, ESCAPE-MeVO, DISCOUNT) did not show clear benefit and raised safety concerns, and intra-arterial tenecteplase remains a relatively novel approach with limited large randomized evidence to date.

Eligibility criteria

Inclusion Criteria:

1. Age ≥18 years
2. Pre-stroke mRS score 0-1
3. Baseline NIHSS ≥4 or symptoms deemed clearly disabling by treating physician (e.g., hemianopia, aphasia, or motor dysfunction)
4. Isolated medium distal vessel occlusion (i.e., an occlusion of the co-/non-dominant M2, the M3/M4 segment of the MCA, the A1/A2/A3 segment of the ACA or the P1/P2/P3 segment of the PCA) confirmed by CT angiography (CTA) or MR angiography (MRA)
5. Acute ischemic stroke within 24 hours of symptom onset, including wake-up stroke or unwitnessed stroke; The onset time of symptoms was defined as the last time of normal performance.
6. Acute ischemic stroke within 6-24 hours of onset, meeting at least one of the following imaging criteria:

   1. Evidence of a hypoperfusion-ischemic core mismatch on CT or MRI perfusion, defined as an ischemic core volume \<50mL, hypoperfused tissue volume to ischemic core volume ratio ≥1.2, and mismatch volume ≥10 mL
   2. Evidence of a diffusion-hyperintensity mismatch, defined as absence of hyperintensity on fluidattenuated inversion recovery (FLAIR) imaging within ≥ 90% of the area of the diffusion weighted imaging (DWI) lesion)
7. The participant or legally authorized representative is capable of providing informed consent

Exclusion Criteria:

1. Evidence of intracranial hemorrhage
2. Any active bleeding (gastrointestinal, urinary, hemorrhagic retinopathy, etc.) or parenchymal organ surgery or biopsy within 30 days before stroke; Severe head trauma or stroke within the past 3 months
3. Persistent and uncontrolled hypertension, defined as systolic blood pressure \>185 mmHg or diastolic blood pressure \>110 mmHg
4. Inherited or acquired hemorrhagic tendancy; deficiency of anticoagulant factors; or on oral anticoagulant with an INR\> 1.7
5. Blood glucose \<2.8 mmol/L (50 mg/dl) or \> 22.2mmol/L (400 mg/dl), platelets count \<100\*109/L, or hemoglobin \<70g/L
6. Severe hepatic insufficiency, chronic hemodialysis and severe renal insufficiency (or recent blood tests suggesting a glomerular filtration rate \<30 ml/min or blood creatinine\> 200 mmol/L (2.5 mg/dl)
7. Women who are pregnant or breastfeeding
8. Allergy to rhTNK-tPA or radiocontrast agent
9. Participation in other clinical trials
10. Expected survival time less than 6 months (e.g., due to malignancy, severe cardiopulmonary disease, etc.)
11. Other conditions deemed by the investigator to make the patient unsuitable for participation or pose significant risks (e.g., inability to understand and/or comply with study procedures and/or follow-up due to mental illness, cognitive or emotional disorders)

Where this trial is running

Wuhan, Hubei

• Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology — Wuhan, Hubei, China (RECRUITING)

Study contacts

• Principal investigator: Xiang Luo — Tongji Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 450001
• Study coordinator: Xiang Luo, PhD, MD

Conditions: Acute Ischemic Stroke, Medium Vessel Occlusion, medium vessel occlusion, Intra-arterial thrombolysis, Tenecteplase