Using alteplase after thrombectomy for acute ischemic stroke

Intra-arterial Alteplase for Acute Ischemic Stroke After Mechanical Thrombectomy (PEARL): A Multicenter, Prospective, Open-label, Blinded Endpoint, Randomized Controlled Trial

This study is testing if giving a specific medication after a procedure to remove a blood clot can help people who have had an acute ischemic stroke recover better than standard treatment alone.

Quick facts

• Phase: PHASE3
• Study type: Interventional
• Enrollment: 324 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University (other)
• Locations: 2 sites (Guangzhou, Guangdong and 1 other locations)
• Trial ID: NCT05856851 on ClinicalTrials.gov

What this trial studies

This multicenter, prospective, open-label, blinded endpoint, randomized controlled trial aims to evaluate the efficacy and safety of intra-arterial recombinant human tissue plasminogen activator (rt-PA) administered after successful mechanical thrombectomy for acute ischemic stroke. Participants will be randomly assigned to receive either intra-arterial alteplase or standard medical treatment following their procedure. The primary outcome will be assessed using the modified Rankin scale (mRS) at 90 days post-treatment, focusing on functional outcomes. A total of 324 participants are expected to be enrolled in the study.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with a clinical diagnosis of acute ischemic stroke and specific imaging-confirmed occlusions.

Not a fit: Patients with contraindications to rt-PA or those requiring dual antiplatelet therapy within the first 24 hours post-thrombectomy may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could significantly improve functional outcomes for patients suffering from acute ischemic stroke.

How similar studies have performed: Previous studies have shown promise in using rt-PA in similar contexts, but this specific approach is being evaluated in a novel setting.

Eligibility criteria

Inclusion Criteria:

1. Aged 18 years or older.
2. Clinical diagnosis of acute ischemic stroke.
3. Time from symptom onset to randomization within 24 hours, including wake-up stroke or no-witness stroke; the onset time refers to "Last Known Well" (LKW).
4. CTA or MRA confirmed occlusion of the intracranial segment of the internal carotid artery, or M1 or M2 segment of the middle cerebral artery; stable eTICI score of 2b50-3 after mechanical thrombectomy, with or without intravenous thrombolysis. Patients with an eTICI score of 2b50-3 on the diagnostic cerebral angiography before mechanical thrombectomy are also eligible for the study.
5. Baseline NIHSS of 6-25.
6. NCCT/DWI-MRI ASPECTS ≥ 6;
7. Pre-stroke mRS score ≤ 1, or mRS \>1 but not related to neurological disease (e.g., amputation, blindness).
8. Signed informed consent.

Exclusion Criteria:

1. Contraindication to rt-PA (except time to therapy).
2. Planned use of dual antiplatelet therapy within the first 24 hours after mechanical thrombectomy.
3. Angiographic evaluation showing dissection, severe stenosis, or complete occlusion of the carotid artery, which requires the use of carotid artery stents during the endovascular procedure.
4. Suspected cerebral vasculitis based on medical history and/or angiographic evaluation.
5. Women who are pregnant or breastfeeding.
6. Participation in other clinical trials.
7. Preoperative intracranial hemorrhage confirmed by cranial CT or MRI.
8. Known genetic or acquired bleeding disposition with anticoagulation factor deficiency.
9. Coagulation disorder with INR \> 1.7 or use of new oral anticoagulants (within 48 hours of symptom onset).
10. Platelet count \<50X10\^9/L.
11. Suspected vascular occlusion as a result of infective endocarditis.
12. Known severe renal insufficiency with glomerular filtration rate \<30 ml/min or blood creatinine \>220 μmol/L (2.5 mg/dl).
13. Severe allergy to contrast (non-mild rash allergy) or absolute contraindication to iodine contrast.
14. Suspected aortic dissection.
15. Previous parenchymal organ surgery or biopsy in the last 1 month;
16. Any active bleeding or recent bleeding (gastrointestinal, urinary tract bleeding, etc.) in the last 1 month;
17. SBP \> 185 mmHg or DBP \> 110 mmHg refractory to treatment.
18. Anticipated life expectancy \< 6 months (e.g., malignancy, severe cardiopulmonary disease, etc.).
19. 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 and 1 other locations

• Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University — Guangzhou, Guangdong, China (RECRUITING)
• Shenzhen Hospital of Southern Medical University — Shenzhen, Guangdong, China (RECRUITING)

Study contacts

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

Conditions: Stroke, Acute Ischemic