Alteplase-Tenecteplase Trial Evaluation for Stroke Thrombolysis - Pilot Phase (ATTEST)
Overview
- Phase
- Phase 2
- Intervention
- Tenecteplase
- Conditions
- Stroke
- Sponsor
- NHS Greater Glasgow and Clyde
- Enrollment
- 104
- Locations
- 1
- Primary Endpoint
- Percent penumbral salvage at 24-48h (initial penumbra volume on computed tomography perfusion (CTP) imaging versus 24-48h CT infarct volume.
- Status
- Completed
- Last Updated
- 7 years ago
Overview
Brief Summary
A pilot evaluation of tenecteplase compared to alteplase in acute ischaemic stroke patients currently eligible for intravenous alteplase treatment in a prospective, randomised, blinded outcome evaluation clinical trial using brain imaging as a biomarker.
Detailed Description
Newer thrombolytic agents such as tenecteplase have pharmacological features (higher fibrin binding specificity and longer half-life) that may be advantageous when compared to older agents such as alteplase with respect to arterial recanalisation, ease of administration, and reduced bleeding risk. No other clinical trial is currently evaluating alternative thrombolytic strategies in patients who are eligible to receive standard intravenous alteplase, instead concentrating on extending the population for IV thrombolysis. The ATTEST pilot phase will use brain imaging as a biomarker for key clinical response variables, with penumbral salvage as the primary end-point and secondary end-points including recanalisation as well as conventional clinical scales. The findings of this study are anticipated to provide data on sample size and event rates to inform the design of a definitive, confirmatory, pragmatic, randomised, controlled trial with clinical endpoints.
Investigators
Eligibility Criteria
Inclusion Criteria
- •clinical diagnosis of supratentorial acute ischaemic stroke with score of at least 1 on the NIH Stroke Scale
- •male or non pregnant female \>=18 years
- •within 4.5 hours of onset as defined by time since last known well
- •CT perfusion and CT Angiogram examination acquired prior to treatment
Exclusion Criteria
- •Contraindications to thrombolytic drug treatment for stroke
- •Evidence of intracranial haemorrhage or significant non-stroke intracranial pathology (including central nervous system neoplasm, aneurysm or arteriovenous malformation) on pre-treatment CT
- •Established hypodensity on pre-treatment brain CT of more than one third of the middle cerebral artery territory or Alberta Stroke Programme Early CT (ASPECT) Score \<4 (sulcal effacement or loss of grey-white differentiation in cortical territories alone are not counted towards ASPECT score)
- •Hypodensity consistent with recent cerebral ischaemia other than the presenting event
- •Very severe stroke (eg NIHSS\>25)
- •systolic blood pressure (BP)\> 185 or diastolic BP\> 110 mm Hg, or aggressive management (intravenous pharmacotherapy) necessary to reduce BP to these limits
- •If on warfarin, International Normalised Ratio (INR) \<1.4
- •Current prescription of non-warfarin oral anticoagulant drugs
- •Significant abnormality of coagulation parameters pre-treatment (prolonged INR or activated partial thromboplastin time (APTT), or platelet count \<100,000/mm3)
- •administration of heparin within the previous 48 hours and a thromboplastin time exceeding the upper limit of normal for laboratory, or use of therapeutic dose low molecular weight heparin within 48h
Arms & Interventions
Tenecteplase 0.25 mg/kg
Intravenous tenecteplase 0.25 mg/kg (single bolus, maximum 25 mg)
Intervention: Tenecteplase
Alteplase 0.9 mg/kg
Intravenous alteplase 0.9 mg/kg (10% bolus and 90% as IV infusion over 1 hour, maximum 90 mg)
Intervention: alteplase
Outcomes
Primary Outcomes
Percent penumbral salvage at 24-48h (initial penumbra volume on computed tomography perfusion (CTP) imaging versus 24-48h CT infarct volume.
Time Frame: 48 hours
Percent penumbral salvage at 24-48h (initial CTP-defined penumbra volume versus 24-48h CT infarct volume.
Secondary Outcomes
- Proportion of patients with symptomatic intracerebral haemorrhage (SICH) on 24-48 hour CT(48 hours)
- Distribution of functional outcome scores (mRS) at Day 90(90 days)
- Proportion of patients with favourable clinical outcome (mRS 0-1) at Day 90(90 days)
- Distribution of functional outcome by modified Rankin Scale (mRS) scores at Day 30(30 Days)
- Proportion of patients exhibiting recanalisation (on computed tomography angiography, CTA) 24-48 hours post treatment(48 hours)
- Mortality at Day 90(90 Days)
- Early clinical improvement 24 hours post treatment(24 hours)
- Proportion of patients with favourable clinical outcome (mRS 0-1) at Day 30(30 days)
- Average 'home time' by day 90(90 Days)