Intra-arterial Alteplase for Acute Ischemic Stroke After Mechanical Thrombectomy

NCT05856851 | Recruiting Phase 3

• 1 other identifier: SYSKY-2023-390-02
• Study Type: interventional
• Target: 324
• Locations: 1 country
• Sites: 2

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.

Conditions

Stroke, Acute Ischemic

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (7)

• Change of infarct volume from baseline

  7(±1) days

• The volume of Tmax>6s on CTP

  24(±12) hours

• The shift analysis of the modified Rankin Scale (mRS)

  90(±7) days

• The modified Rankin Scale score (mRS) 0-2

  90(±7) days

• The modified Rankin Scale score (mRS) 0-3

  90(±7) days

Other Outcomes (3)

• SAFETY OUTCOME: Symptomatic intracranial hemorrhage

  24 (±12) hours

• SAFETY OUTCOME: Mortality

  90(±7) days

• SAFETY OUTCOME: Any intracranial hemorrhage

  24 (±12) hours

Study Arms (2)

Intra-arterial alteplase

EXPERIMENTAL

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

Standard medical treatment

NO INTERVENTION

Participants allocated to the control group will receive standard medical treatment without intra-arterial alteplase after mechanical thrombectomy.

Interventions

Alteplase DRUG

See arm/group descriptions.

Also known as: Intra-arterial alteplase after mechanical thrombectomy

Intra-arterial alteplase

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged 18 years or older.
• Clinical diagnosis of acute ischemic stroke.
• 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).
• 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.
• Baseline NIHSS of 6-25.
• NCCT/DWI-MRI ASPECTS ≥ 6;
• Pre-stroke mRS score ≤ 1, or mRS \>1 but not related to neurological disease (e.g., amputation, blindness).
• Signed informed consent.

You may not qualify if:

• Contraindication to rt-PA (except time to therapy).
• Planned use of dual antiplatelet therapy within the first 24 hours after mechanical thrombectomy.
• 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.
• Suspected cerebral vasculitis based on medical history and/or angiographic evaluation.
• Women who are pregnant or breastfeeding.
• Participation in other clinical trials.
• Preoperative intracranial hemorrhage confirmed by cranial CT or MRI.
• Known genetic or acquired bleeding disposition with anticoagulation factor deficiency.
• Coagulation disorder with INR \> 1.7 or use of new oral anticoagulants (within 48 hours of symptom onset).
• Platelet count \<50X10\^9/L.
• Suspected vascular occlusion as a result of infective endocarditis.
• Known severe renal insufficiency with glomerular filtration rate \<30 ml/min or blood creatinine \>220 μmol/L (2.5 mg/dl).
• Severe allergy to contrast (non-mild rash allergy) or absolute contraindication to iodine contrast.
• Suspected aortic dissection.
• Previous parenchymal organ surgery or biopsy in the last 1 month;

Sponsors & Collaborators

• Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University: lead
• Shenzhen Hospital of Southern Medical University: collaborator

Study Sites (2)

Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University

Guangzhou, Guangdong, 510120, China

RECRUITING

Shenzhen Hospital of Southern Medical University

Shenzhen, Guangdong, China

RECRUITING

Related Publications (1)

• Yang X, He X, Pan D, Xu Y, Peng H, Li K, Zhang M, Zhu Y, Chen Y, He B, Zhou H, Li J, Hou H, Sun H, Liu Y, Tang Y. Intra-arterial alteplase for acute ischaemic stroke after mechanical thrombectomy (PEARL): rationale and design of a multicentre, prospective, open-label, blinded-endpoint, randomised controlled trial. BMJ Open. 2024 Nov 5;14(11):e091059. doi: 10.1136/bmjopen-2024-091059.

  PMID: 39500603 DERIVED

MeSH Terms

Conditions

Ischemic Stroke

Interventions

Tissue Plasminogen Activator

Condition Hierarchy (Ancestors)

Stroke; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Serine Endopeptidases; Endopeptidases; Peptide Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Serine Proteases; Plasminogen Activators; Blood Coagulation Factors; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Biological Factors

Study Officials

• Yamei Tang

  Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

  PRINCIPAL INVESTIGATOR

• Yajie Liu

  Shenzhen Hospital of Southern Medical University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Xinguang Yang

CONTACT

86-20-81332619; yangxinguang0926@163.com

Xiongjun He

CONTACT

075523360593; drxjhe@163.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 4, 2023
• First Posted: May 12, 2023
• Study Start: August 1, 2023
• Primary Completion: December 1, 2025
• Study Completion: December 1, 2025
• Last Updated: September 3, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: 6 months after the trial completion.
• Access Criteria: The IPD will be available from Principal Investigators (Prof. Yamei Tang and Prof. Yajie Liu) upon reasonable request.

Locations

CN (2)