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Ischemic stroke is a major health burden globally and in Australia. Treatment for ischemic stroke is time critical and is significantly more effective if administered within the first 90 minutes of symptom onset. This clinical trial will identify if early administration of oral thrombolytic agent, tenecteplase prior to hospital can improve outcomes from stroke, and reduce costs compared to standard care of IV alteplase in hospital
Currently, alteplase is the standard clot-dissolving therapy for ischemic stroke, however this treatment is only effective in 30-45% of patients. Importantly, treatment of ischemic stroke is more effective when given within 90 minutes of stroke onset. Means of treating patients earlier with more effective therapies are needed.
Ischemic stroke is a major public health problem, for which effective and accessible drug therapies remain limited. Current management of acute ischemic stroke includes treatment with a solution called alteplase, which dissolves clots in a cerebral artery. The treatment effect of alteplase is much greater if given within 90 minutes of stroke onset.
As a result, there has been a significant push to take stroke care to the patient in the form of the Mobile Stroke Unit (MSU). The MSU is the first designed as a CT-capable ambulance that allows assessment and treatment of stroke patients in the pre-hospital setting. In the proposed research project, we will undertake a clinical trail investigating the effectiveness of a new thrombolytic agent in the MSU, tenecteplase.
Tenecteplase has been shown to be significantly more effective at improving stroke survivor's recovery and opening blocked blood vessels than alteplase in the hospital setting. However, it is unknown if earlier administration of tenecteplase is more effective than early administration of alteplase.
The tested agent, tenecteplase, is cheaper, easier to administer (no time-consuming infusions required) and more practical for an ambulance delivered therapy than the current standard of care alteplase. If tenecteplase results in better clinical outcomes in addition to these practical advantages, there is significant scope for improved patient outcomes and cost savings.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Intravenous tenecteplase (TNK) | Active Comparator | Patients will receive intravenous tenecteplase (0.25mg/kg, maximum 25mg, administered as a bolus over ~10 seconds). |
|
| Intravenous tissue plasminogen activator (tPA) | Active Comparator | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Tenecteplase | Drug | Route: IV bolus injection Frequency: once only, within 4.5 hours of stroke onset |
|
| Measure | Description | Time Frame |
|---|---|---|
| Perfusion lesion on CTP | The volume of the perfusion lesion on CTP performed on arrival at the receiving hospital, adjusted for pre-treatment NIHSS and time from initiation of treatment to CTP. | Within 2hrs of treatment |
| Measure | Description | Time Frame |
|---|---|---|
| Infarct core growth between baseline CTP and 24 hour MRI. | 24 hrs | |
| Percent reperfusion between baseline CTP and 24 hour perfusion imaging (MRI) | 24 hrs | |
| Reduction in NIHSS between pre-treatment score and score on ED arrival, adjusted for pre-treatment NIHSS and time from initiation of treatment to ED NIHSS score |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Royal Melbourne Hospital | Melbourne | Victoria | 3050 | Australia | ||
| Eastern Health |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 35525251 | Derived | Bivard A, Zhao H, Churilov L, Campbell BCV, Coote S, Yassi N, Yan B, Valente M, Sharobeam A, Balabanski AH, Dos Santos A, Ng JL, Yogendrakumar V, Ng F, Langenberg F, Easton D, Warwick A, Mackey E, MacDonald A, Sharma G, Stephenson M, Smith K, Anderson D, Choi P, Thijs V, Ma H, Cloud GC, Wijeratne T, Olenko L, Italiano D, Davis SM, Donnan GA, Parsons MW; TASTE-A collaborators. Comparison of tenecteplase with alteplase for the early treatment of ischaemic stroke in the Melbourne Mobile Stroke Unit (TASTE-A): a phase 2, randomised, open-label trial. Lancet Neurol. 2022 Jun;21(6):520-527. doi: 10.1016/S1474-4422(22)00171-5. Epub 2022 May 4. | |
| 35487712 |
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| ID | Term |
|---|---|
| D000083242 | Ischemic Stroke |
| ID | Term |
|---|---|
| D020521 | Stroke |
| D002561 | Cerebrovascular Disorders |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
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| ID | Term |
|---|---|
| D000077785 | Tenecteplase |
| D010959 | Tissue Plasminogen Activator |
| ID | Term |
|---|---|
| D012697 | Serine Endopeptidases |
| D010450 | Endopeptidases |
| D010447 | Peptide Hydrolases |
| D006867 | Hydrolases |
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Multicentre, prospective, randomised open-label blinded endpoint (PROBE) phase II study in stroke thrombolysis patients to compare tenecteplase and alteplase for an outcome of less disability at 3 months
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The people assessing the outcomes The people analysing the results/data
| Intravenous tissue plasminogen activator (tPA) | Drug | Route: Intravenous (IV) infusion (10% as bolus and the remainder over 60 minutes) Frequency: once only, within 4.5 hours of stroke onset |
|
|
| 2 hrs |
| Reduction in NIHSS between pre-treatment score and score at 24 hours post treatment, adjusted for pre-treatment NIHSS | 24 hrs |
| Modified Rankin Scale (mRS) at 3 months - ordinal analysis adjusted for baseline NIHSS and age | 3 months |
| mRS 0-2 or no change from baseline at 3 months adjusted for baseline NIHSS and age | 3 months |
| Proportion of patients where thrombolytic medication is initiated within 5 minutes of completion of CT on the MSU. | 24 hrs |
| Time from completion of CT on the MSU to initiation of thrombolysis (CT to needle time) | 2 hrs |
| mRS 5-6 at 3 months adjusted for baseline NIHSS and age | 3 months |
| Death due to any cause adjusted for baseline NIHSS and age | During time on study up to 3 months |
| Any parenchymal haematoma | During time on study up to 3 months |
| ymptomatic intracranial hemorrhage (sICH) | During time on study up to 3 months |
| Melbourne |
| Victoria |
| Australia |
| Western Hospital | Melbourne | Victoria | Australia |
| Alfred Hopsital | Melbourne | Australia |
| Monash Health | Melbourne | Australia |
| Derived |
| Bivard A, Zhao H, Coote S, Campbell B, Churilov L, Yassi N, Yan B, Valente M, Sharobeam A, Balabanski A, Dos Santos A, Ng F, Langenberg F, Stephenson M, Smith K, Bernard S, Thijs V, Cloud G, Choi P, Ma H, Wijeratne T, Chen C, Olenko L, Davis SM, Donnan GA, Parsons M. Tenecteplase versus Alteplase for Stroke Thrombolysis Evaluation Trial in the Ambulance (Mobile Stroke Unit-TASTE-A): protocol for a prospective randomised, open-label, blinded endpoint, phase II superiority trial of tenecteplase versus alteplase for ischaemic stroke patients presenting within 4.5 hours of symptom onset to the mobile stroke unit. BMJ Open. 2022 Apr 29;12(4):e056573. doi: 10.1136/bmjopen-2021-056573. |
| D009422 |
| Nervous System Diseases |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D004798 |
| Enzymes |
| D045762 | Enzymes and Coenzymes |
| D057057 | Serine Proteases |
| D010960 | Plasminogen Activators |
| D001779 | Blood Coagulation Factors |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D001685 | Biological Factors |