Determining the Optimal Dose of Tenecteplase Before Endovascular Therapy for Ischaemic Stroke (EXTEND-IA TNK Part 2)

March 2, 2020 updated by: Neuroscience Trials Australia

EXTEND-IA TNK: Extending the Time for Thrombolysis in Emergency Neurological Deficits - Intra-Arterial Using Intravenous Tenecteplase Part 2

Patients presenting to the emergency department with acute ischemic stroke, who are eligible for standard intravenous thrombolysis 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 either 0.4mg/kg or 0.25mg/kg intravenous tenecteplase before all participants undergo endovascular thrombectomy. The trial is prospective, randomised, open-label, blinded endpoint (PROBE) design.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

The study will be a multicentre, prospective, randomized, open- label, blinded endpoint (PROBE), controlled phase 2 trial (2 arm with 1:1 randomization) in ischemic stroke patients.

Randomized patients will first be stratified by both the setting of treatment: metropolitan hospital vs regional hospital (>1 hour transfer to endovascular centre) vs mobile stroke unit; and by site of baseline arterial occlusion: Intracranial internal carotid artery (ICA) and Basilar artery versus Middle cerebral artery (MCA - M1 and M2); overall resulting in six strata.

Imaging is performed with CT or MR (magnetic resonance) acutely as part of standard care with imaging follow-up at 18-30 hours. The sequences and the parameters used follow the STIR (Stroke Imaging Research) roadmap guidelines, but imaging takes place acutely and at 18- 30hrs only, as previously validated.

The sample size estimation was based on the proportion of pre-endovascular reperfusion observed in the 0.25mg/kg group from Part 1 of EXTEND-IA TNK (22%). An estimated total sample size of 188 patients (with 94 patients in each of treatment and control arms) yielded 80% power to detect a significant difference of 20% in strata-weighted angiographic reperfusion (mTICI 2b/3) at initial angiogram (22% in 0.25mg/kg vs 42% in 0.4mg/kg arm) at two-sided statistical significance threshold of p=0.05 for superiority. Adaptive increase in sample size will be performed if the result of interim analysis using data from the first 150 patients is promising, as per the methodology of Mehta and Pocock.

During the trial, blinded analysis of operational characteristics revealed a 20% reduction in the time from thrombolysis to arterial access versus part 1 due to improved workflow (In the first 150 patients in part 2 median 37min [IQR 19-54] versus 46min [IQR 28-63] in part 1). This directly impacts the time for thrombolysis to have an effect. A 20% reduction in the hypothesized rate of reperfusion at initial angiogram (18% vs 33%) would require 145 patients per group. Allowing for potential further improvements in workflow the sample size re-estimation was postponed from 150 to 240 patients with a revised minimum sample of 300 patients. Adaptive increase in sample size will be performed if the result of interim analysis using data from the first 240 patients is promising, as per the methodology of Mehta and Pocock. The maximum sample size is capped at 656 patients.

Study Type

Interventional

Enrollment (Actual)

300

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
    • New South Wales
      • Albury, New South Wales, Australia, 2640
        • Albury Hospital
      • Bankstown, New South Wales, Australia, 2200
        • Bankstown-Lidcombe Hospital
      • Campbelltown, New South Wales, Australia, 2560
        • Campbelltown Hospital
      • Camperdown, New South Wales, Australia, 2050
        • Royal Prince Alfred Hospital
      • Gosford, New South Wales, Australia, 2250
        • Gosford Hospital
      • Liverpool, New South Wales, Australia, 2170
        • Liverpool Hospital
      • Newcastle, New South Wales, Australia
        • John Hunter Hospital
      • St Leonards, New South Wales, Australia, 2605
        • Royal North Shore Hospital
      • Westmead, New South Wales, Australia, 2145
        • Westmead Hospital
    • Queensland
      • Brisbane, Queensland, Australia
        • Royal Brisbane & Women's Hospital
      • Gold Coast, Queensland, Australia
        • Gold Coast University Hospital
      • Nambour, Queensland, Australia, 4560
        • Sunshine Coast University Hospital
      • Woolloongabba, Queensland, Australia, 4102
        • Princess Alexandra Hospital
    • South Australia
      • Adelaide, South Australia, Australia, 5000
        • Royal Adelaide Hospital
      • Elizabeth Vale, South Australia, Australia, 5112
        • Lyell McEwin Hospital
    • Victoria
      • Ballarat, Victoria, Australia, 3353
        • Ballarat Health Services
      • Box Hill, Victoria, Australia, 3128
        • Box Hill Hospital
      • Clayton, Victoria, Australia, 3168
        • Monash Medical Centre
      • Heidelberg, Victoria, Australia
        • Austin Hospital
      • Melbourne, Victoria, Australia, 3050
        • Royal Melbourne Hospital
      • Melbourne, Victoria, Australia, 3004
        • Alfred Hospital
      • Shepparton, Victoria, Australia, 3630
        • Goulburn Valley Health
      • St Albans, Victoria, Australia, 3021
        • Western Heath
      • Traralgon, Victoria, Australia, 3844
        • Latrobe Regional Hospital
      • Wangaratta, Victoria, Australia, 3677
        • North East Health Wangaratta
      • Warrnambool, Victoria, Australia, 3280
        • South West Healthcare
  • New Zealand
      • Christchurch, New Zealand, 8011
        • Christchurch Hospital
    • Auckland
      • Grafton, Auckland, New Zealand, 1001
        • Auckland Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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
  • Arterial occlusion on CTA (computed tomography angiography) or MRA (Magnetic Resonance Angiography) 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Assigned Interventions
Patients will receive intravenous tenecteplase (0.25mg/kg, maximum 25mg, administered as a bolus over ~10 seconds).
Drug: Tenecteplase
Tenecteplase 0.25mg/kg and 0.4mg/kg are being used
Other Names:
  • TNK
Experimental: Tenecteplase
Patients will receive intravenous tenecteplase (0.4mg/kg, maximum 40mg, administered as a bolus over ~10 seconds).
Drug: Tenecteplase
Tenecteplase 0.25mg/kg and 0.4mg/kg are being used
Other Names:
  • TNK

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
mTICI
Time Frame: Initial angiogram (day 0)
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

Outcome Measure
Measure Description
Time Frame
Modified Rankin Scale (mRS)
Time Frame: at 3 months post stroke
mRS ordinal analysis. mRS 0-1 or no change from baseline and mRS 0-2 or no change from baseline.
at 3 months post stroke
National Institutes of Health Stroke Scale (NIHSS)
Time Frame: Initial angiogram (day 0)
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)
Symptomatic intracranial haemorrhage (SICH)
Time Frame: Within 36 hours post treatment
SICH is defined as "Intracerebral hemorrhage (parenchymal hematoma type 2 - PH2 within 36 hours of treatment) combined with neurological deterioration leading to an increase of ≥4 points on the NIHSS"
Within 36 hours post treatment
Death
Time Frame: Up to 3 months post stroke
Death due to any cause
Up to 3 months post stroke
Angiographic reperfusion
Time Frame: Up to 24 hours post treatment
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Neuroscience Trials Australia

Collaborators

The Florey Institute of Neuroscience and Mental Health

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 6, 2017

Primary Completion (Actual)

July 23, 2019

Study Completion (Actual)

February 1, 2020

Study Registration Dates

First Submitted

November 8, 2017

First Submitted That Met QC Criteria

November 9, 2017

First Posted (Actual)

November 13, 2017

Study Record Updates

Last Update Posted (Actual)

March 4, 2020

Last Update Submitted That Met QC Criteria

March 2, 2020

Last Verified

March 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NTA1401a

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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