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

Ischemic Stroke Clinical Trial

— EXTEND-IA  

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.

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01492725
• Other study ID #: NTA1101
• Status: Terminated
• Phase: Phase 2
• First received: November 20, 2011
• Last updated: April 20, 2015
• Start date: June 2012
• Est. completion date: December 2014

Study information

• Verified date: December 2014
• Source: Neuroscience Trials Australia
• Contact: n/a
• Is FDA regulated: No
• Health authority: Australia: Department of Health and Ageing Therapeutic Goods Administration
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 70
• Est. completion date: December 2014
• Est. primary completion date: December 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Patients presenting with anterior circulation acute ischaemic stroke eligible using standard criteria to receive IV tPA within 4.5 hours of stroke onset

2. Patient, family member or legally responsible person depending on local ethics requirements has given informed consent

3. Patient?s age is =18 years

4. Intra-arterial clot retrieval treatment can commence (groin puncture) within 6 hours of stroke onset.

Imaging inclusion criteria

Dual target:

5. Arterial occlusion on CTA or MRA of the ICA, M1 or M2

6. 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:

1. Intracranial haemorrhage (ICH) identified by CT or MRI

2. Rapidly improving symptoms at the discretion of the investigator

3. Pre-stroke mRS score of = 2 (indicating previous disability)

4. Inability to access the cerebral vasculature in the opinion of the neurointerventional team

5. Contra indication to imaging with MR with contrast agents

6. Participation in any investigational study in the previous 30 days

7. Any terminal illness such that patient would not be expected to survive more than 1 year

8. 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.

9. Pregnant women

10. Previous stroke within last three months

11. 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.

12. Current use of oral anticoagulants and a prolonged prothrombin time (INR > 1.6)

13. 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.

14. 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.

15. Clinically significant hypoglycaemia.

16. 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.

17. Hereditary or acquired haemorrhagic diathesis

18. Gastrointestinal or urinary bleeding within the preceding 21 days

19. Major surgery within the preceding 14 days which poses risk in the opinion of the investigator.

20. Exposure to a thrombolytic agent within the previous 72 hrs

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Ischemic Stroke

Intervention

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.

Genetic:
• intravenous tissue plasminogen activator (tPA)
Standard care IV tPA therapy administered as per registered product information

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital	Adelaide	South Australia
Australia	Austin Hospital	Melbourne	Victoria
Australia	Box Hill Hospital	Melbourne	Victoria
Australia	Monash Medical Centre	Melbourne	Victoria
Australia	Royal Melbourne Hospital	Melbourne	Victoria
Australia	Western Hospital	Melbourne	Victoria
Australia	John Hunter Hospital	New Lambton Heights	New South Wales
Australia	Royal North Shore Hospital	St Leonards	New South Wales
New Zealand	Auckland Hospital	Grafton	Auckland

Sponsors (1)

Lead Sponsor	Collaborator
Neuroscience Trials Australia

Countries where clinical trial is conducted

Australia,  New Zealand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Reperfusion at 24 hours (CT or MR perfusion imaging)		24 hours post stroke onset	No
Primary	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	No
Secondary	Reperfusion at 24 hrs post stroke without symptomatic intracerebral hemorrhage (CT or MR perfusion imaging)		24 hours post stroke onset	Yes
Secondary	Recanalisation at 24 hrs post stroke (CT or MR angiography)		24 hours post stroke onset	No
Secondary	Infarct growth within 24 hrs (CT and MRI)		24 hours post stroke onset	No
Secondary	Stroke severity (NIHSS) at 24 hours		24 hours post stroke onset	No
Secondary	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	Yes
Secondary	Death due to any cause		3 months	Yes
Secondary	Modified Rankin Scale (mRS) 0-1 at 3 months		3 months	No
Secondary	Categorical shift in mRS at 3 months		3 months	No
Secondary	NIHSS reduction 8 points or reaching 0-1 at 3 months		3 months	No
Secondary	Modified Rankin Scale (mRS) 0-2 at 3 months		3 months	No