Extending the Time for Thrombolysis in Emergency Neurological Deficits - Intra-Arterial (EXTEND-IA)
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Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
Ischemic Stroke |
Device: Intra-arterial Clot Retrieval with Solitaire device Genetic: intravenous tissue plasminogen activator (tPA) |
Phase 2 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | 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. |
- Reperfusion at 24 hours (CT or MR perfusion imaging) [ Time Frame: 24 hours post stroke onset ] [ Designated as safety issue: No ]
- Favourable clinical response at 3 days(National Institutes of Health Stroke Score - NIHSS) [ Time Frame: 3 days post stroke onset ] [ Designated as safety issue: No ]NIHSS - reduction >/= 8 points or reaching 0-1)
- Reperfusion at 24 hrs post stroke without symptomatic intracerebral hemorrhage (CT or MR perfusion imaging) [ Time Frame: 24 hours post stroke onset ] [ Designated as safety issue: Yes ]
- Recanalisation at 24 hrs post stroke (CT or MR angiography) [ Time Frame: 24 hours post stroke onset ] [ Designated as safety issue: No ]
- Infarct growth within 24 hrs (CT and MRI) [ Time Frame: 24 hours post stroke onset ] [ Designated as safety issue: No ]
- Stroke severity (NIHSS) at 24 hours [ Time Frame: 24 hours post stroke onset ] [ Designated as safety issue: No ]
- 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). [ Time Frame: within 36 hours of intervention ] [ Designated as safety issue: Yes ]
- Death due to any cause [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]
- Modified Rankin Scale (mRS) 0-1 at 3 months [ Time Frame: 3 months ] [ Designated as safety issue: No ]
- Categorical shift in mRS at 3 months [ Time Frame: 3 months ] [ Designated as safety issue: No ]
- NIHSS reduction 8 points or reaching 0-1 at 3 months [ Time Frame: 3 months ] [ Designated as safety issue: No ]
- Modified Rankin Scale (mRS) 0-2 at 3 months [ Time Frame: 3 months ] [ Designated as safety issue: No ]
| Estimated Enrollment: | 100 |
| Study Start Date: | June 2012 |
| Estimated Study Completion Date: | December 2014 |
| Estimated Primary Completion Date: | December 2014 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
| Experimental: Intra-arterial Clot Retrieval after iv tPA |
Device: Intra-arterial Clot Retrieval with Solitaire device
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.
|
| Active Comparator: Standard care iv tPA |
Genetic: intravenous tissue plasminogen activator (tPA)
Standard care IV tPA therapy administered as per registered product information
|
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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
- Patient‟s 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
Contacts and Locations| Contact: Bruce Dr Campbell | +61 3 9342 7000 | bruce.campbell@mh.org.au |
| Australia, New South Wales | |
| John Hunter Hospital | Recruiting |
| New Lambton Heights, New South Wales, Australia, 2305 | |
| Contact: Mark Parsons, Dr. mark.parsons@hnehealth.nsw.gov.au | |
| Principal Investigator: Mark Parsons, Dr | |
| Royal North Shore Hospital | Recruiting |
| St Leonards, New South Wales, Australia, 2605 | |
| Contact: Martin Krause, A/Prof. | |
| Principal Investigator: Martin Krause, A/Prof. | |
| Australia, South Australia | |
| Royal Adelaide Hospital | Recruiting |
| Adelaide, South Australia, Australia, 5000 | |
| Contact: Timothy Kleinig, Dr. | |
| Principal Investigator: Timothy kleinig, Dr. | |
| Australia, Victoria | |
| Royal Melbourne Hospital | Recruiting |
| Melbourne, Victoria, Australia | |
| Contact: Stephen Davis | |
| Principal Investigator: Stephen Davis | |
| Austin Hospital | Recruiting |
| Melbourne, Victoria, Australia, 3084 | |
| Principal Investigator: Helen Dewey | |
| Box Hill Hospital | Recruiting |
| Melbourne, Victoria, Australia, 3128 | |
| Contact: Christopher Bladin | |
| Principal Investigator: Christopher Bladin | |
| Monash Medical Centre | Recruiting |
| Melbourne, Victoria, Australia, 3168 | |
| Contact: Thanh Phan | |
| Principal Investigator: Than Phan | |
| Western Hospital | Recruiting |
| Melbourne, Victoria, Australia, 3011 | |
| Contact: Tissa Wijeratne | |
| Principal Investigator: Tissa Wijeratne | |
| New Zealand | |
| Auckland Hospital | Recruiting |
| Grafton, Auckland, New Zealand, 1001 | |
| Contact: Alan Barber, Prof. | |
| Principal Investigator: Alan Barber, Prof. | |
More Information
No publications provided
| Responsible Party: | National Stroke Research Institute, Australia |
| ClinicalTrials.gov Identifier: | NCT01492725 History of Changes |
| Other Study ID Numbers: | NTA1101 |
| Study First Received: | November 20, 2011 |
| Last Updated: | April 30, 2013 |
| Health Authority: | Australia: Department of Health and Ageing Therapeutic Goods Administration |
Additional relevant MeSH terms:
|
Stroke Cerebral Infarction Cerebrovascular Disorders Brain Diseases Central Nervous System Diseases Nervous System Diseases Vascular Diseases Cardiovascular Diseases Brain Infarction Brain Ischemia |
Plasminogen Tissue Plasminogen Activator Fibrinolytic Agents Fibrin Modulating Agents Molecular Mechanisms of Pharmacological Action Pharmacologic Actions Cardiovascular Agents Therapeutic Uses Hematologic Agents |
ClinicalTrials.gov processed this record on June 17, 2013