Adding intra-arterial clot-busting therapy to endovascular treatment for medium-vessel stroke

OPtimizing REperfusion by Intra-Arterial ThRomboLysis as Adjunct to Endovascular Treatment for Medium Vessel Occlusion (PEARL-MeVO): A Multicenter, Prospective, Randomized Controlled, Open-label, Blinded-Endpoint Clinical Trial

It tests whether adding intra-arterial clot-busting medicine to endovascular treatment helps adults with medium-vessel acute ischemic stroke who can be treated within 24 hours recover better.

Quick facts

• Phase: PHASE3
• Study type: Interventional
• Enrollment: 530 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University (other)
• Locations: 1 site (Guangzhou, Guangdong)
• Trial ID: NCT07137832 on ClinicalTrials.gov

What this trial studies

PEARL-MeVO randomizes 530 adults with acute ischemic stroke due to isolated medium vessel occlusion to receive either intra-arterial thrombolysis plus endovascular treatment or standard medical management alone in a 1:1 ratio. The trial is prospective, multicenter and open-label with blinded endpoint assessment (PROBE), enrolling patients treated within 6 hours or within 6–24 hours when perfusion imaging shows salvageable brain tissue. The primary outcome is the proportion of patients achieving a modified Rankin Scale score of 0–1 at 90 days, with safety and secondary functional outcomes also tracked. Imaging-based core and mismatch criteria and a baseline NIHSS ≥6 are used to select eligible patients.

Who should consider this trial

Good fit: Adults (≥18) with acute ischemic stroke from an isolated medium vessel occlusion, NIHSS ≥6, who can begin arterial puncture within 6 hours or within 6–24 hours with imaging evidence of salvageable tissue and who can provide informed consent.

Not a fit: Patients with intracranial hemorrhage, pre-stroke disability (mRS ≥2), a large established ischemic core (>50 mL), rapidly improving symptoms, or who cannot meet the specified timing or imaging criteria are unlikely to receive benefit from this approach.

Why it matters

Potential benefit: If successful, adding intra-arterial thrombolysis could increase the chance of excellent 90-day recovery (mRS 0–1) for patients with medium-vessel occlusion treated endovascularly.

How similar studies have performed: Endovascular therapy is well established for large-vessel occlusions and small observational reports have suggested potential benefit from adjunct intra-arterial thrombolysis in smaller occlusions, but randomized phase 3 evidence for this specific adjunct in medium-vessel occlusion is limited.

Eligibility criteria

Inclusion Criteria:

1. Aged 18 years or older.
2. Clinical diagnosis of acute ischemic stroke.
3. CT angiography (CTA) or MR angiography (MRA) confirmed primary isolated medium 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).
4. Baseline NIHSS ≥6.
5. Treatment (arterial puncture) can be initiated 5.1 Within 6 hours of last known well (LKW) OR 5.2 Within 6 to 24 hours of LKW AND evidence of salvageable brain tissue on CT perfusion or perfusion-diffusion MRI (ischemic core volume \<50mL, hypo-perfused tissue volume to ischemic core volume ratio \>1.4, mismatch volume \>10mL). Hypo-perfused tissue is defined as Tmax \>6s on CT perfusion or perfusion MRI. Ischemic core is defined as rCBF \<30% on CT perfusion or ADC \<620μm2/s on diffusion MRI.
6. Signed informed consent.

Exclusion Criteria:

1. Evidence of intracranial hemorrhage.
2. Pre-stroke mRS score ≥ 2.
3. Rapidly improving symptoms, in the judgment of the managing clinician that the improvement is likely to result in the patient having an NIHSS score of \<6 at randomization.
4. The intervention procedure is unlikely to be completed as assessed by the investigator.
5. Suspected cerebral vasculitis, septic embolization, or vascular occlusion due to infective endocarditis.
6. Suspected arterial dissection.
7. Severe allergy to contrast agents (non-mild rash allergy) or absolute contraindication to iodine contrast.
8. Known genetic or acquired bleeding disposition or anticoagulant factors deficiency.
9. Coagulation disorder with INR \>1.7 or use of new oral anticoagulants within 48 hours prior to symptom onset.
10. Platelet count \<50×10\^9/L.
11. Any active or recent bleeding (gastrointestinal, urinary tract bleeding, etc.), or previous parenchymal organ surgery or biopsy in the last 1 month.
12. Systolic blood pressure \>185 mmHg or diastolic blood pressure \>110 mmHg, refractory to treatment.
13. Known severe renal insufficiency with glomerular filtration rate \<30 ml/min or blood creatinine \>220 μmol/L (2.5 mg/dl).
14. Radiological confirmed evidence of mass effect or intracranial tumour (except small meningioma).
15. Anticipated life expectancy \<6 months due to advanced disease (e.g., malignancy, severe cardiopulmonary disease, etc.).
16. Women who are pregnant or breastfeeding.
17. Participation in other clinical trials.
18. 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).

Where this trial is running

Guangzhou, Guangdong

• Sun Yat-sen Memorial Hospital, Sun Yat-sen University — Guangzhou, Guangdong, China (RECRUITING)

Study contacts

• Principal investigator: Yamei Tang — Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
• Study coordinator: Zhenhong Deng

Conditions: Acute Ischemic Stroke