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

NCT ID: NCT03340493

Last Updated: 2020-03-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 300 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-12-06
• Study Completion Date: 2020-02-01

Brief Summary

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.

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.

Conditions

Ischemic Stroke

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Assigned Interventions

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

Group Type: ACTIVE_COMPARATOR

Tenecteplase

Intervention Type: DRUG

Tenecteplase 0.25mg/kg and 0.4mg/kg are being used

Tenecteplase

Patients will receive intravenous tenecteplase (0.4mg/kg, maximum 40mg, administered as a bolus over \~10 seconds).

Group Type: EXPERIMENTAL

Tenecteplase

Intervention Type: DRUG

Tenecteplase 0.25mg/kg and 0.4mg/kg are being used

Interventions

Tenecteplase

Tenecteplase 0.25mg/kg and 0.4mg/kg are being used

Intervention Type: DRUG

Other Intervention Names

TNK

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The Florey Institute of Neuroscience and Mental Health

OTHER

Sponsor Role: collaborator

Neuroscience Trials Australia

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Albury Hospital

Albury, New South Wales, Australia

Bankstown-Lidcombe Hospital

Bankstown, New South Wales, Australia

Campbelltown Hospital

Campbelltown, New South Wales, Australia

Royal Prince Alfred Hospital

Camperdown, New South Wales, Australia

Gosford Hospital

Gosford, New South Wales, Australia

Liverpool Hospital

Liverpool, New South Wales, Australia

John Hunter Hospital

Newcastle, New South Wales, Australia

Royal North Shore Hospital

St Leonards, New South Wales, Australia

Westmead Hospital

Westmead, New South Wales, Australia

Royal Brisbane & Women's Hospital

Brisbane, Queensland, Australia

Gold Coast University Hospital

Gold Coast, Queensland, Australia

Sunshine Coast University Hospital

Nambour, Queensland, Australia

Princess Alexandra Hospital

Woolloongabba, Queensland, Australia

Royal Adelaide Hospital

Adelaide, South Australia, Australia

Lyell McEwin Hospital

Elizabeth Vale, South Australia, Australia

Ballarat Health Services

Ballarat, Victoria, Australia

Box Hill Hospital

Box Hill, Victoria, Australia

Monash Medical Centre

Clayton, Victoria, Australia

Austin Hospital

Heidelberg, Victoria, Australia

Alfred Hospital

Melbourne, Victoria, Australia

Royal Melbourne Hospital

Melbourne, Victoria, Australia

Goulburn Valley Health

Shepparton, Victoria, Australia

Western Heath

St Albans, Victoria, Australia

Latrobe Regional Hospital

Traralgon, Victoria, Australia

North East Health Wangaratta

Wangaratta, Victoria, Australia

South West Healthcare

Warrnambool, Victoria, Australia

Auckland Hospital

Grafton, Auckland, New Zealand

Christchurch Hospital

Christchurch, , New Zealand

Countries

Australia; New Zealand

References

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Other Identifiers

NTA1401a

Identifier Type: -

Identifier Source: org_study_id