Extending the Time for Thrombolysis in Emergency Neurological Deficits - Intra-Arterial

Study Overview
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Brief Summary
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Patients presenting to the emergency department with acute ischaemic stroke, who are eligible for standard intravenous tPA therapy within 4.5 hours of stroke onset will be assessed for dual target major vessel occlusion and mismatch to determine their eligibility for randomisation into the trial. If the patient gives informed consent they will be randomised 50:50 using central computerised allocation to intra-arterial clot retrieval after IV tPA or IV tPA alone. The trial is prospective, randomised, open-label, blinded endpoint (PROBE) design.

Official Title
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A Randomized Controlled Trial of Intra-arterial Reperfusion Therapy After Standard Dose Intravenous t-PA Within 4.5 Hours of Stroke Onset Utilizing Dual Target Imaging Selection.

Conditions
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Ischemic Stroke

Intervention / Treatment
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* Device: Intra-arterial Clot Retrieval with Solitaire device
* Genetic: intravenous tissue plasminogen activator (tPA)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients presenting with anterior circulation acute ischaemic stroke eligible using standard criteria to receive IV tPA within 4.5 hours of stroke onset Patient, family member or legally responsible person depending on local ethics requirements has given informed consent Patients age is ≥18 years Intra-arterial clot retrieval treatment can commence (groin puncture) within 6 hours of stroke onset. Imaging inclusion criteria Dual target: Arterial occlusion on CTA or MRA of the ICA, M1 or M2 Mismatch - Using CT or MRI with a Tmax >6 second delay perfusion volume and either CT-rCBF or DWI infarct core volume. a) Mismatch ratio of greater than 1.2, and b) Absolute mismatch volume of greater than 10 ml, and. c) Infarct core lesion volume of less than 70mL Exclusion Criteria: Intracranial haemorrhage (ICH) identified by CT or MRI Rapidly improving symptoms at the discretion of the investigator Pre-stroke mRS score of ≥ 2 (indicating previous disability) Inability to access the cerebral vasculature in the opinion of the neurointerventional team Contra indication to imaging with MR with contrast agents Participation in any investigational study in the previous 30 days Any terminal illness such that patient would not be expected to survive more than 1 year Any condition that, in the judgment of the investigator could impose hazards to the patient if study therapy is initiated or affect the participation of the patient in the study. Pregnant women Previous stroke within last three months Recent past history or clinical presentation of ICH, subarachnoid haemorrhage (SAH), arterio-venous (AV) malformation, aneurysm, or cerebral neoplasm. At the discretion of each Investigator. Current use of oral anticoagulants and a prolonged prothrombin time (INR > 1.6) Use of heparin, except for low dose subcutaneous heparin, in the previous 48 hours and a prolonged activated partial thromboplastin time exceeding the upper limit of the local laboratory normal range. Use of glycoprotein IIb - IIIa inhibitors within the past 72 hours. Prior use of single or dual agent oral platelet inhibitors (clopidogrel and/or low-dose aspirin) is permitted. Clinically significant hypoglycaemia. Uncontrolled hypertension defined by a blood pressure > 185 mmHg systolic or >110 mmHg diastolic on at least 2 separate occasions at least 10 minutes apart, or requiring aggressive treatment to reduce the blood pressure to within these limits. The definition of aggressive treatment is left to the discretion of the responsible Investigator. Hereditary or acquired haemorrhagic diathesis Gastrointestinal or urinary bleeding within the preceding 21 days Major surgery within the preceding 14 days which poses risk in the opinion of the investigator. Exposure to a thrombolytic agent within the previous 72 hrs

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intra-arterial Clot Retrieval after iv tPA<br> | Device: Intra-arterial Clot Retrieval with Solitaire device<br>* Intra-arterial mechanical clot retrieval with the Solitaire device after patients have received standard therapy with intravenous tissue plasminogen activator (tPA). Clot retrieval involves cerebral angiography and takes approximately 2 hours.<br>|
| Active Comparator: Standard care iv tPA<br> | Genetic: intravenous tissue plasminogen activator (tPA)<br>* Standard care IV tPA therapy administered as per registered product information<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reperfusion at 24 hours (CT or MR perfusion imaging) |  | 24 hours post stroke onset | 
| Favourable clinical response at 3 days(National Institutes of Health Stroke Score - NIHSS) | NIHSS - reduction >/= 8 points or reaching 0-1) | 3 days post stroke onset | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reperfusion at 24 hrs post stroke without symptomatic intracerebral hemorrhage (CT or MR perfusion imaging) |  | 24 hours post stroke onset | 
| Recanalisation at 24 hrs post stroke (CT or MR angiography) |  | 24 hours post stroke onset | 
| Infarct growth within 24 hrs (CT and MRI) |  | 24 hours post stroke onset | 
| Stroke severity (NIHSS) at 24 hours |  | 24 hours post stroke onset | 
| Symptomatic intra-cranial hemorrhage (ECASS type 2 parenchymal hematoma on CT or MRI combined with >/=4 point deterioration in NIHSS within 36 hours of treatment). |  | within 36 hours of intervention | 
| Death due to any cause |  | 3 months | 
| Modified Rankin Scale (mRS) 0-1 at 3 months |  | 3 months | 
| Categorical shift in mRS at 3 months |  | 3 months | 
| NIHSS reduction 8 points or reaching 0-1 at 3 months |  | 3 months | 
| Modified Rankin Scale (mRS) 0-2 at 3 months |  | 3 months |