Clinical trial NCT05856851: Intra-arterial Alteplase for Acute Ischemic Stroke After Mechanical Thrombectomy
Official title: Intra-arterial Alteplase for Acute Ischemic Stroke After Mechanical Thrombectomy (PEARL): A Multicenter, Prospective, Open-label, Blinded Endpoint, Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Stroke, Acute Ischemic
Lead sponsor: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
Sponsor class: OTHER
Collaborators: name: Shenzhen Hospital of Southern Medical University
First posted: 2023-05-12
Enrollment: 324
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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 20 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.

A total of 324 participants are anticipated to be recruited for this study, with 162 participants in each group (1:1 ratio).

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).

Primary outcomes:
measure: The modified Rankin Scale score (mRS) 0-1
timeFrame: 90(±7) days
Secondary outcomes:
measure: Change of infarct volume from baseline
timeFrame: 7(±1) days
measure: The volume of Tmax>6s on CTP
timeFrame: 24(±12) hours
measure: The shift analysis of the modified Rankin Scale (mRS)
timeFrame: 90(±7) days
measure: The modified Rankin Scale score (mRS) 0-2
timeFrame: 90(±7) days
measure: The modified Rankin Scale score (mRS) 0-3
timeFrame: 90(±7) days
measure: The proportion of NIHSS 0-1 or ≥10 points reduction
timeFrame: 48 (±12) hours
measure: Quality of Life (EQ-5D-5L)
timeFrame: 90(±7) days
Other outcomes:
measure: SAFETY OUTCOME: Symptomatic intracranial hemorrhage
timeFrame: 24 (±12) hours
measure: SAFETY OUTCOME: Mortality
timeFrame: 90(±7) days
measure: SAFETY OUTCOME: Any intracranial hemorrhage
timeFrame: 24 (±12) hours
Locations:
city: Guangzhou
country: China
facility: Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University
state: Guangdong
city: Shenzhen
country: China
facility: Shenzhen Hospital of Southern Medical University
state: Guangdong
Study officials:
affiliation: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
name: Yamei Tang
role: PRINCIPAL_INVESTIGATOR
affiliation: Shenzhen Hospital of Southern Medical University
name: Yajie Liu
role: PRINCIPAL_INVESTIGATOR
References: