Determining the Optimal Dose of Tenecteplase Before Endovascular Therapy for Ischaemic Stroke (EXTEND-IA TNK Part 2)
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT03340493|
Recruitment Status : Active, not recruiting
First Posted : November 13, 2017
Last Update Posted : August 22, 2019
|Condition or disease||Intervention/treatment||Phase|
|Ischemic Stroke||Drug: Tenecteplase||Phase 2|
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 (Clinical Trial)|
|Estimated Enrollment :||188 participants|
|Intervention Model:||Parallel Assignment|
|Intervention Model Description:||Patients will receive either intravenous tenecteplase (0.4mg/kg, maximum 40mg, administered as a bolus over ~10 seconds) or intravenous tenecteplase (0.25mg/kg, maximum 25mg, administered as a bolus over ~10 seconds).|
|Masking:||Single (Outcomes Assessor)|
|Masking Description:||Blinded core laboratory adjudication of the primary outcome. NIHSS and mRS (secondary outcomes) performed by blinded assessor.|
|Official Title:||EXTEND-IA TNK: Extending the Time for Thrombolysis in Emergency Neurological Deficits - Intra-Arterial Using Intravenous Tenecteplase Part 2|
|Actual Study Start Date :||December 6, 2017|
|Actual Primary Completion Date :||July 23, 2019|
|Estimated Study Completion Date :||March 1, 2020|
Active Comparator: Assigned Interventions
Patients will receive intravenous tenecteplase (0.25mg/kg, maximum 25mg, administered as a bolus over ~10 seconds).
Tenecteplase 0.25mg/kg and 0.4mg/kg are being used
Other Name: TNK
Patients will receive intravenous tenecteplase (0.4mg/kg, maximum 40mg, administered as a bolus over ~10 seconds).
Tenecteplase 0.25mg/kg and 0.4mg/kg are being used
Other Name: TNK
- 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.
- 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.
- 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
- 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"
- Death [ Time Frame: Up to 3 months post stroke ]Death due to any cause
- 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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03340493
|Australia, New South Wales|
|Albury, New South Wales, Australia, 2640|
|Bankstown, New South Wales, Australia, 2200|
|Campbelltown, New South Wales, Australia, 2560|
|Royal Prince Alfred Hospital|
|Camperdown, New South Wales, Australia, 2050|
|Gosford, New South Wales, Australia, 2250|
|Liverpool, New South Wales, Australia, 2170|
|John Hunter Hospital|
|Newcastle, New South Wales, Australia|
|Royal North Shore Hospital|
|St Leonards, New South Wales, Australia, 2605|
|Westmead, New South Wales, Australia, 2145|
|Royal Brisbane & Women's Hospital|
|Brisbane, Queensland, Australia|
|Gold Coast University Hospital|
|Gold Coast, Queensland, Australia|
|Sunshine Coast University Hospital|
|Nambour, Queensland, Australia, 4560|
|Princess Alexandra Hospital|
|Woolloongabba, Queensland, Australia, 4102|
|Australia, South Australia|
|Royal Adelaide Hospital|
|Adelaide, South Australia, Australia, 5000|
|Lyell McEwin Hospital|
|Elizabeth Vale, South Australia, Australia, 5112|
|Ballarat Health Services|
|Ballarat, Victoria, Australia, 3353|
|Box Hill Hospital|
|Box Hill, Victoria, Australia, 3128|
|Monash Medical Centre|
|Clayton, Victoria, Australia, 3168|
|Heidelberg, Victoria, Australia|
|Melbourne, Victoria, Australia, 3004|
|Royal Melbourne Hospital|
|Melbourne, Victoria, Australia, 3050|
|Goulburn Valley Health|
|Shepparton, Victoria, Australia, 3630|
|St Albans, Victoria, Australia, 3021|
|Latrobe Regional Hospital|
|Traralgon, Victoria, Australia, 3844|
|North East Health Wangaratta|
|Wangaratta, Victoria, Australia, 3677|
|South West Healthcare|
|Warrnambool, Victoria, Australia, 3280|
|Grafton, Auckland, New Zealand, 1001|
|Christchurch, New Zealand, 8011|