PEARL: Intra-arterial Alteplase for Acute Ischemic Stroke After Mechanical Thrombectomy
Study Details
Study Description
Brief Summary
A multicenter, prospective, open-label, blinded endpoint, randomized controlled trial aiming at evaluating the efficacy and safety of intra-arterial recombinant human tissue plasminogen activator (rt-PA) after successful recanalization of acute large vessel occlusion in the anterior circulation by mechanical thrombectomy in improving the 90-day functional outcome.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 3 |
Detailed Description
This study is a multicenter, prospective, open-label, blinded endpoint, randomized controlled trial designed to evaluate the efficacy and safety of intra-arterial recombinant human tissue plasminogen activator (rt-PA) after successful recanalization of acute large vessel occlusion in the anterior circulation by mechanical thrombectomy (eTICI 2b50/3). The primary outcome is the proportion of patients with a 90-day modified Rankin scale (mRS) of 0-1.
Study intervention: (1) Participants in the experimental group will receive intra-arterial alteplase (a dose of 0.225 mg/kg and a maximum dose of 22.5 mg) after the mechanical thrombectomy, and will receive standard medical treatment after the procedure. (2) Participants in the control group will receive standard medical treatment without intra-arterial alteplase.
This study will enroll a total of 232 participants, with 116 participants in each group (1:1 ratio).
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Intra-arterial alteplase Participants in the experimental group will receive a 15-minute continuous infusion of intra-arterial alteplase at a drug concentration of 1.0 mg/ml. 15 minutes after the start of intra-arterial thrombolysis, the infusion will be stopped and an angiogram will be performed to assess the eTICI score. If the angiographic eTICI score improves from the baseline score, the procedure will be terminated, otherwise, a new angiogram will be repeated 5-10 minutes after the end of drug administration. |
Drug: Alteplase
See arm/group descriptions.
Other Names:
|
| No Intervention: Standard medical treatment Participants allocated to the control group will receive standard medical treatment without intra-arterial alteplase after mechanical thrombectomy. |
Outcome Measures
Primary Outcome Measures
- The modified Rankin Scale score (mRS) 0-1 [90(±7) days]
The proportion of the modified Rankin Scale score (mRS) 0-1 at 90 days.
Secondary Outcome Measures
- Change of infarct volume from baseline [7(±1) days]
The change of infarct volume at 7(±1) days or discharge (whichever occurred first) on non-contrast CT, or at 48(±12) hours on MRI
- The volume of Tmax>6s on CTP [24(±12) hours]
The volume of Tmax>6s on CTP at 24(±12) hours
- The shift analysis of the modified Rankin Scale (mRS) [90(±7) days]
The shift analysis of the modified Rankin Scale (mRS) at 90 days
- The modified Rankin Scale score (mRS) 0-2 [90(±7) days]
The proportion of the modified Rankin Scale score (mRS) 0-2 at 90 days.
- The modified Rankin Scale score (mRS) 0-3 [90(±7) days]
The proportion of the modified Rankin Scale score (mRS) 0-3 at 90 days.
- The proportion of NIHSS 0-1 or ≥10 points reduction [48 (±12) hours]
The proportion of NIHSS 0-1 or ≥10 points reduction at 48 (±12) hours
- Quality of Life (EQ-5D-5L) [90(±7) days]
The value of Quality of Life (EQ-5D-5L) at 90 days
Other Outcome Measures
- SAFETY OUTCOME: Symptomatic intracranial hemorrhage [24 (±12) hours]
Symptomatic intracranial hemorrhage within 36 hours (according to Heidelberg criteria)
- SAFETY OUTCOME: Mortality [90(±7) days]
Mortality at 90 days
- SAFETY OUTCOME: Any intracranial hemorrhage [24 (±12) hours]
Any intracranial hemorrhage within 36 hours (according to Heidelberg criteria)
Eligibility Criteria
Criteria
Inclusion Criteria:
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Aged 18 years or older.
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Clinical diagnosis of acute ischemic stroke.
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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).
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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.
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Baseline NIHSS of 6-25.
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NCCT/DWI-MRI ASPECTS ≥ 6;
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Pre-stroke mRS score ≤ 1, or mRS >1 but not related to neurological disease (e.g., amputation, blindness).
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Signed informed consent.
Exclusion Criteria:
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Contraindication to rt-PA (except time to therapy).
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Planned use of dual antiplatelet therapy within the first 24 hours after mechanical thrombectomy.
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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.
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Suspected cerebral vasculitis based on medical history and/or angiographic evaluation.
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Women who are pregnant or breastfeeding.
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Participation in other clinical trials.
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Preoperative intracranial hemorrhage confirmed by cranial CT or MRI.
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Known genetic or acquired bleeding disposition with anticoagulation factor deficiency.
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Coagulation disorder with INR > 1.7 or use of new oral anticoagulants (within 48 hours of symptom onset).
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Platelet count <50X10^9/L.
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Suspected vascular occlusion as a result of infective endocarditis.
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Known severe renal insufficiency with glomerular filtration rate <30 ml/min or blood creatinine >220 μmol/L (2.5 mg/dl).
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Severe allergy to contrast (non-mild rash allergy) or absolute contraindication to iodine contrast.
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Suspected aortic dissection.
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Previous parenchymal organ surgery or biopsy in the last 1 month;
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Any active bleeding or recent bleeding (gastrointestinal, urinary tract bleeding, etc.) in the last 1 month;
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SBP > 185 mmHg or DBP > 110 mmHg refractory to treatment.
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Anticipated life expectancy < 6 months (e.g., malignancy, severe cardiopulmonary disease, etc.).
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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).
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
- Shenzhen Hospital of Southern Medical University
Investigators
- Principal Investigator: Yamei Tang, Sun Yat-sen Memorial Hospital,Sun Yat-sen University
- Principal Investigator: Yajie Liu, Shenzhen Hospital of Southern Medical University
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- SYSKY-2023-390-01