Alteplase-Tenecteplase Trial Evaluation for Stroke Thrombolysis- (ATTEST)

Sponsor

NHS Greater Glasgow and Clyde (Other)

Overall Status

Completed

CT.gov ID

NCT01472926

Collaborator

University of Glasgow (Other)

104

Enrollment

Location

Arms

24.3

Duration (Months)

4.3

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Stroke	Drug: Tenecteplase Drug: alteplase	Phase 2

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

104 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Alteplase-Tenecteplase Trial Evaluation for Stroke Thrombolysis - Pilot Phase (ATTEST)

Study Start Date :

Dec 1, 2011

Actual Primary Completion Date :

Dec 10, 2013

Actual Study Completion Date :

Dec 10, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Tenecteplase 0.25 mg/kg Intravenous tenecteplase 0.25 mg/kg (single bolus, maximum 25 mg)	Drug: Tenecteplase Intravenous (IV) tenecteplase 0.25 mg/kg (single bolus; maximum dose 25 mg) Other Names: Metalyse TNK
Active Comparator: Alteplase 0.9 mg/kg Intravenous alteplase 0.9 mg/kg (10% bolus and 90% as IV infusion over 1 hour, maximum 90 mg)	Drug: alteplase Intravenous alteplase 0.9mg/kg to maximum of 90mg, given as 10% bolus and 90% of dose over 1 hour infusion Other Names: Actilyse recombinant tissue plasminogen activator (rtPA)

Arm

Intervention/Treatment

Experimental: Tenecteplase 0.25 mg/kg

Intravenous tenecteplase 0.25 mg/kg (single bolus, maximum 25 mg)

Drug: Tenecteplase

Intravenous (IV) tenecteplase 0.25 mg/kg (single bolus; maximum dose 25 mg)

Other Names:

Metalyse

TNK

Active Comparator: Alteplase 0.9 mg/kg

Intravenous alteplase 0.9 mg/kg (10% bolus and 90% as IV infusion over 1 hour, maximum 90 mg)

Drug: alteplase

Intravenous alteplase 0.9mg/kg to maximum of 90mg, given as 10% bolus and 90% of dose over 1 hour infusion

Other Names:

Actilyse

recombinant tissue plasminogen activator (rtPA)

Outcome Measures

Primary Outcome Measures

Percent penumbral salvage at 24-48h (initial penumbra volume on computed tomography perfusion (CTP) imaging versus 24-48h CT infarct volume. [48 hours]
Percent penumbral salvage at 24-48h (initial CTP-defined penumbra volume versus 24-48h CT infarct volume.

Secondary Outcome Measures

Proportion of patients exhibiting recanalisation (on computed tomography angiography, CTA) 24-48 hours post treatment [48 hours]
Proportion of patients exhibiting recanalisation (measured by CTA) 24-48 hours post treatment
Early clinical improvement 24 hours post treatment [24 hours]
Early clinical improvement (National Institutes of Health Stroke Scale [NIHSS] score reduced by >=4 points, or = 0 or 1) 24 hours post treatment
Proportion of patients with symptomatic intracerebral haemorrhage (SICH) on 24-48 hour CT [48 hours]
Proportion of patients with symptomatic ICH (SICH) on 24-48 hour CT: by Safe Implementation of Thrombolysis Monitoring Study (SITS-MOST) definition - parenchymal haematoma type 2 (PH2/PHr2) + NIHSS deterioration by >=4 points at 24 hours Any ICH
Distribution of functional outcome by modified Rankin Scale (mRS) scores at Day 30 [30 Days]
Distribution of outcome scores on the modified Rankin Scale (mRS)
Distribution of functional outcome scores (mRS) at Day 90 [90 days]
Distribution of functional outcome scores (mRS)
Proportion of patients with favourable clinical outcome (mRS 0-1) at Day 30 [30 days]
Proportion of patients with favourable clinical outcome (mRS 0-1)
Proportion of patients with favourable clinical outcome (mRS 0-1) at Day 90 [90 days]
Proportion of patients with favourable clinical outcome (mRS 0-1)
Average 'home time' by day 90 [90 Days]
Average 'home time' (number of nights spent in non-institutional private residence) by Day 90
Mortality at Day 90 [90 Days]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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
Clinical history suggestive of subarachnoid haemorrhage even if no blood is evident on CT
Risk of bleeding (Major surgery within previous 1 month; intracranial or spinal surgery; recent trauma to the head or cranium; prolonged cardiopulmonary resuscitation (> 2 minutes) within the past 2 weeks; acute pericarditis and/or subacute bacterial endocarditis; acute pancreatitis; severe hepatic dysfunction, including hepatic failure, cirrhosis, portal hypertension (oesophageal varices) and active hepatitis; active peptic ulceration; any known history of haemorrhagic stroke or stroke of unknown origin; arterial aneurysm and known arteriovenous malformation)
Dependent (mRS 3-5) pre-stroke
Blood glucose <2 mmol/l or >18 mmol/l
Seizure at onset of symptoms unless brain imaging identifies positive evidence of significant brain ischaemia (eg CTA confirmed arterial occlusion, early ischaemic change on plain CT, hypoperfusion on CTP)
Pregnancy
Known impaired renal function (estimated Glomerular Filtration Rate <30 ml/min) precluding contrast CT
Known allergy to radiological contrast
History of allergies to active substances in either trial medication, or to excipients including gentamicin
Severe concurrent medical condition that would prevent participation in study procedures (e.g. cardia failure with severe pulmonary oedema)or with life expectancy <=3 months