Clinical trial NCT04071613: Tenecteplase Versus Alteplase for Stroke Thrombolysis Evaluation Trial in the Ambulance
Official title: Tenecteplase Versus Alteplase for Stroke Thrombolysis Evaluation Trial in the Ambulance
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Stroke, Acute, Stroke Ischemic
Lead sponsor: Melbourne Health
Sponsor class: OTHER
First posted: 2019-08-28
Enrollment: 104
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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
Primary purpose: TREATMENT

Brief summary: 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

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

1. Patients being attended by the mobile stroke unit with an acute ischemic stroke eligible for thrombolysis using standard clinical and CT criteria.
2. Patient's age is ≥18 years
3. Premorbid mRS \<4

Exclusion Criteria:

1. Intracranial hemorrhage (ICH) or other diagnosis (e.g. tumor) identified by CT on the MSU
2. Hypodensity in \>1/3 MCA territory or equivalent proportion of ACA or PCA territory on non-contrast CT on MSU
3. Pre-stroke mRS score of \> 3 (indicating significant previous disability)
4. Any terminal illness such that patient would not be expected to survive more than 1 year
5. 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.
6. Pregnant women.
7. Rapidly improving symptoms.

Primary outcomes:
measure: Perfusion lesion on CTP
timeFrame: Within 2hrs of treatment
Secondary outcomes:
measure: Infarct core growth between baseline CTP and 24 hour MRI.
timeFrame: 24 hrs
measure: Percent reperfusion between baseline CTP and 24 hour perfusion imaging (MRI)
timeFrame: 24 hrs
measure: 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
timeFrame: 2 hrs
measure: Reduction in NIHSS between pre-treatment score and score at 24 hours post treatment, adjusted for pre-treatment NIHSS
timeFrame: 24 hrs
measure: Modified Rankin Scale (mRS) at 3 months - ordinal analysis adjusted for baseline NIHSS and age
timeFrame: 3 months
measure: mRS 0-2 or no change from baseline at 3 months adjusted for baseline NIHSS and age
timeFrame: 3 months
measure: Proportion of patients where thrombolytic medication is initiated within 5 minutes of completion of CT on the MSU.
timeFrame: 24 hrs
measure: Time from completion of CT on the MSU to initiation of thrombolysis (CT to needle time)
timeFrame: 2 hrs
measure: mRS 5-6 at 3 months adjusted for baseline NIHSS and age
timeFrame: 3 months
measure: Death due to any cause adjusted for baseline NIHSS and age
timeFrame: During time on study up to 3 months
measure: Any parenchymal haematoma
timeFrame: During time on study up to 3 months
measure: ymptomatic intracranial hemorrhage (sICH)
timeFrame: During time on study up to 3 months
Other outcomes:
Locations:
city: Melbourne
country: Australia
facility: Royal Melbourne Hospital
state: Victoria
city: Melbourne
country: Australia
facility: Eastern Health
state: Victoria
city: Melbourne
country: Australia
facility: Western Hospital
state: Victoria
city: Melbourne
country: Australia
facility: Alfred Hopsital
city: Melbourne
country: Australia
facility: Monash Health
Study officials:
References:
citation: 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.
citation: 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.