Intra-arterial Alteplase for Acute Ischemic Stroke After Mechanical Thrombectomy (PEARL)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Stroke, Acute Ischemic
• Intervention / Treatment: Drug: Alteplase

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).

• Study Type: Interventional
• Enrollment (Estimated): 324
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Xinguang Yang; Phone Number: 86-20-81332619; Email: yangxinguang0926@163.com
• Study Contact Backup: Name: Xiongjun He; Phone Number: 075523360593; Email: drxjhe@163.com

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510120
      • Recruiting
      • Sun Yat-sen Memorial Hospital, Sun Yat-sen University
      • Contact: Xinguang Yang, M.D.; Email: yangxinguang0926@163.com
      • Principal Investigator: Yamei Tang, M.D., PhD.
    • Shenzhen, Guangdong, China
      • Recruiting
      • Shenzhen Hospital of Southern Medical University
      • Contact: Xiongjun He, M.D., Ph.D.; Email: drxjhe@163.com
      • Principal Investigator: Yajie Liu, M.D., Ph.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / 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: Intra-arterial alteplase after mechanical thrombectomy
No Intervention: Standard medical treatment; Participants allocated to the control group will receive standard medical treatment without intra-arterial alteplase after mechanical thrombectomy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The modified Rankin Scale score (mRS) 0-1	The proportion of the modified Rankin Scale score (mRS) 0-1 at 90 days.	90(±7) days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of infarct volume from baseline	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	7(±1) days
The volume of Tmax>6s on CTP	The volume of Tmax>6s on CTP at 24(±12) hours	24(±12) hours
The shift analysis of the modified Rankin Scale (mRS)	The shift analysis of the modified Rankin Scale (mRS) at 90 days	90(±7) days
The modified Rankin Scale score (mRS) 0-2	The proportion of the modified Rankin Scale score (mRS) 0-2 at 90 days.	90(±7) days
The modified Rankin Scale score (mRS) 0-3	The proportion of the modified Rankin Scale score (mRS) 0-3 at 90 days.	90(±7) days
The proportion of NIHSS 0-1 or ≥10 points reduction	The proportion of NIHSS 0-1 or ≥10 points reduction at 48 (±12) hours	48 (±12) hours
Quality of Life (EQ-5D-5L)	The value of Quality of Life (EQ-5D-5L) at 90 days	90(±7) days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
SAFETY OUTCOME: Symptomatic intracranial hemorrhage	Symptomatic intracranial hemorrhage within 36 hours (according to Heidelberg criteria)	24 (±12) hours
SAFETY OUTCOME: Mortality	Mortality at 90 days	90(±7) days
SAFETY OUTCOME: Any intracranial hemorrhage	Any intracranial hemorrhage within 36 hours (according to Heidelberg criteria)	24 (±12) hours

Collaborators and Investigators

• Sponsor: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
• Collaborators: 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 record dates

Study Major Dates

• Study Start (Actual): August 1, 2023
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: May 4, 2023
• First Submitted That Met QC Criteria: May 4, 2023
• First Posted (Actual): May 12, 2023

Study Record Updates

• Last Update Posted (Actual): August 14, 2023
• Last Update Submitted That Met QC Criteria: August 7, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Stroke; Ischemic Stroke; Ischemia; Molecular Mechanisms of Pharmacological Action; Fibrinolytic Agents; Fibrin Modulating Agents; Tissue Plasminogen Activator
• Other Study ID Numbers: SYSKY-2023-390-02

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No