A Phase 2 interventional study of Tenecteplase in Ischemic Stroke, sponsored by Neuroscience Trials Australia. Completed at 28 sites in 2 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2020-03-04.
Sponsored by Neuroscience Trials Australia · Phase 2, Interventional, and Treatment
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.
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.
2,612 studies on the registry are indexed under Ischemic Stroke; 971 are open to participants now.
This study's enrollment of 300 is above the median of 120 across 1,776 interventional studies indexed under Ischemic Stroke.
Browse Ischemic Stroke studies →Neuroscience Trials Australia is the lead sponsor of 12 studies on the registry; none are open to participants now.
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Exclusion Criteria:
Patients will receive intravenous tenecteplase (0.25mg/kg, maximum 25mg, administered as a bolus over \~10 seconds).
Drug: 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
Also known as: TNK
mTICI
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.
Time frame: Initial angiogram (day 0)
Modified Rankin Scale (mRS)
mRS ordinal analysis. mRS 0-1 or no change from baseline and mRS 0-2 or no change from baseline.
Time frame: at 3 months post stroke
National Institutes of Health Stroke Scale (NIHSS)
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
Time frame: Initial angiogram (day 0)
Symptomatic intracranial haemorrhage (SICH)
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"
Time frame: Within 36 hours post treatment
Death
Death due to any cause
Time frame: Up to 3 months post stroke
Angiographic reperfusion
Proportion of patients with angiographic reperfusion adjusted for hyperdense clot length on non-contrast CT and time from thrombolysis to initial angiogram
Time frame: Up to 24 hours post treatment
Ran from Dec 2017 to primary completion in Jul 2019, 19 months.
Of 83 non-industry phase 2 interventional studies under Ischemic Stroke, half reached primary completion within 28 months of starting (the median), counting those still running; a quarter within 15 and three quarters within 40. This study's 19 months is below that.
Counting every sponsor, half of 124 studies reached it within 28 months; a quarter within 15 and three quarters within 39.
How these figures are worked out, and which studies are left out of them.
This study is completed, as verified in Mar 2020. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: Tenecteplase
Neuroscience Trials Australia