EXTEND-IA TNK: Tenecteplase Versus Alteplase Before Endovascular Therapy for Ischemic Stroke

Sponsor

Neuroscience Trials Australia (Other)

Overall Status

Completed

CT.gov ID

NCT02388061

Collaborator

The Florey Institute of Neuroscience and Mental Health (Other)

202

Enrollment

Locations

Arms

34.4

Actual Duration (Months)

11.2

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Patients presenting to the emergency department with acute ischemic stroke, who are are eligible for standard intravenous tPA therapy within 4.5 hours of stroke onset will be assessed for major vessel occlusion to determine their eligibility for randomization into the trial. If the patient gives informed consent they will be randomised 50:50 using central computerised allocation to intravenous alteplase or tenecteplase before all participants undergo intra-arterial clot retrieval. The trial is prospective, randomised, open-label, blinded endpoint (PROBE) design.

Condition or Disease	Intervention/Treatment	Phase
Ischemic Stroke	Drug: Tenecteplase Drug: Tissue Plasminogen Activator	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

202 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Mar 23, 2015

Actual Primary Completion Date :

Oct 16, 2017

Actual Study Completion Date :

Feb 1, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Intravenous tenecteplase (TNK) Patients will receive intravenous tenecteplase (0.25mg/kg, maximum 25mg, administered as a bolus over ~10 seconds).	Drug: Tenecteplase Other Names: TNK
Active Comparator: Intravenous tissue plasminogen activator (tPA) Patients will receive intravenous t-PA at the standard licensed dose of 0.9 mg/kg up to a maximum of 90mg, 10% as bolus and the remainder over 1 hour.	Drug: Tissue Plasminogen Activator Other Names: Alteplase tPA

Arm

Intervention/Treatment

Experimental: Intravenous tenecteplase (TNK)

Patients will receive intravenous tenecteplase (0.25mg/kg, maximum 25mg, administered as a bolus over ~10 seconds).

Drug: Tenecteplase

Other Names:

TNK

Active Comparator: Intravenous tissue plasminogen activator (tPA)

Patients will receive intravenous t-PA at the standard licensed dose of 0.9 mg/kg up to a maximum of 90mg, 10% as bolus and the remainder over 1 hour.

Drug: Tissue Plasminogen Activator

Other Names:

Alteplase

tPA

Outcome Measures

Primary Outcome Measures

Proportion of patients with substantial angiographic reperfusion (mTICI) score of 2b/3 (restoration of blood flow to >50% of the affected arterial territory) or absence of retrievable thrombus at initial angiogram. [Initial angiogram (day 0)]

Secondary Outcome Measures

Proportion of patients with ≥8 point reduction in NIHSS or reaching 0-1 at 3 days (favourable clinical response) adjusted for baseline NIHSS and age. [Initial angiogram (day 0)]
Modified Rankin Scale (mRS) at 3 months [3 months post stroke]
ordinal analysis
mRS 0-1 or no change from baseline at 3 months [3 months post stroke]
mRS 0-2 or no change from baseline at 3 months [3 months post stroke]
Symptomatic intracranial hemorrhage (SICH) [within 36 hours post treatment]
Death due to any cause [Up to 3 months post stroke]
Proportion of patients with angiographic reperfusion adjusted for hyperdense clot length on non-contrast CT and time from thrombolysis to initial angiogram [Up to 24 hours post treatment]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patients presenting with acute ischemic stroke eligible using standard criteria to receive IV thrombolysis within 4.5 hours of stroke onset
Patient's age is ≥18 years
Intra-arterial clot retrieval treatment can commence (arterial puncture) within 6 hours of stroke onset.
Arterial occlusion on CTA or MRA of the ICA, M1, M2 or basilar artery.

Exclusion Criteria:

Intracranial hemorrhage (ICH) identified by CT or MRI
Rapidly improving symptoms at the discretion of the investigator
Pre-stroke mRS score of ≥ 4 (indicating previous disability)
Hypodensity in >1/3 MCA territory or equivalent proportion of basilar artery territory on non-contrast CT
Contra indication to imaging with contrast agents
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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Royal Prince Alfred Hospital	Camperdown	New South Wales	Australia	2050
2	Gosford Hospital	Gosford	New South Wales	Australia	2250
3	John Hunter Hospital	Newcastle	New South Wales	Australia
4	Royal North Shore Hospital	St. Leonards	New South Wales	Australia	2065
5	Westmead Hospital	Westmead	New South Wales	Australia	2145
6	Royal Brisbane & Women's Hospital	Brisbane	Queensland	Australia
7	Gold Coast University Hospital	Gold Coast	Queensland	Australia
8	Princess Alexandra Hospital	Woolloongabba	Queensland	Australia	4102
9	Royal Adelaide Hospital	Adelaide	South Australia	Australia	5000
10	Lyell McEwin Hospital	Elizabeth Vale	South Australia	Australia	5112
11	Box Hill Hospital	Box Hill	Victoria	Australia	3128
12	Monash Medical Centre	Clayton	Victoria	Australia	3168
13	Austin Hospital	Heidelberg	Victoria	Australia
14	Alfred Hospital	Melbourne	Victoria	Australia	3004
15	Royal Melbourne Hospital	Melbourne	Victoria	Australia	3050
16	Western Heath	St Albans	Victoria	Australia	3021
17	Auckland Hospital	Grafton	Auckland	New Zealand	1001
18	Christchurch Hospital	Christchurch		New Zealand	8011