Alteplase-Tenecteplase Trial Evaluation for Stroke Thrombolysis- (ATTEST) - Full Text View

Purpose

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	Intervention	Phase
Stroke	Drug: Tenecteplase Drug: alteplase	Phase 2

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Single Blind (Outcomes Assessor) Primary Purpose: Treatment
Official Title:	Alteplase-Tenecteplase Trial Evaluation for Stroke Thrombolysis - Pilot Phase (ATTEST)

Resource links provided by NLM:

Drug Information available for: Alteplase Tenecteplase

U.S. FDA Resources

Further study details as provided by NHS Greater Glasgow and Clyde:

Primary Outcome Measures:

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 ] [ Designated as safety issue: Yes ]
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 [ Time Frame: 48 hours ] [ Designated as safety issue: No ]
Proportion of patients exhibiting recanalisation (measured by CTA) 24-48 hours post treatment
Early clinical improvement 24 hours post treatment [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
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 [ Time Frame: 48 hours ] [ Designated as safety issue: Yes ]
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 [ Time Frame: 30 Days ] [ Designated as safety issue: No ]
Distribution of outcome scores on the modified Rankin Scale (mRS)
Distribution of functional outcome scores (mRS) at Day 90 [ Time Frame: 90 days ] [ Designated as safety issue: No ]
Distribution of functional outcome scores (mRS)
Proportion of patients with favourable clinical outcome (mRS 0-1) at Day 30 [ Time Frame: 30 days ] [ Designated as safety issue: No ]
Proportion of patients with favourable clinical outcome (mRS 0-1)
Proportion of patients with favourable clinical outcome (mRS 0-1) at Day 90 [ Time Frame: 90 days ] [ Designated as safety issue: No ]
Proportion of patients with favourable clinical outcome (mRS 0-1)
Average 'home time' by day 90 [ Time Frame: 90 Days ] [ Designated as safety issue: No ]
Average 'home time' (number of nights spent in non-institutional private residence) by Day 90
Mortality at Day 90 [ Time Frame: 90 Days ] [ Designated as safety issue: No ]

Estimated Enrollment:	104
Study Start Date:	December 2011
Estimated Study Completion Date:	January 2014
Estimated Primary Completion Date:	September 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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)

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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
- 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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01472926

Contacts

Contact: Keith Muir

+44 141 201 2494

keith.muir@glasgow.ac.uk

Locations

United Kingdom
Southern General Hospital	Recruiting
Glasgow, Scotland, United Kingdom, G51 4TF
Principal Investigator: Keith Muir

Sponsors and Collaborators

NHS Greater Glasgow and Clyde

University of Glasgow

Investigators

Study Chair:

Keith Muir

The University of Glasgow

More Information

No publications provided

Responsible Party:	Keith Muir, SINAPSE Professor of Clinical Imaging & Consultant Neurologist, NHS Greater Glasgow and Clyde
ClinicalTrials.gov Identifier:	NCT01472926 History of Changes
Other Study ID Numbers:	2010-024541-67, TSA 2010/04, 2010-024541-67
Study First Received:	November 14, 2011
Last Updated:	August 9, 2012
Health Authority:	United Kingdom: Medicines and Healthcare Products Regulatory Agency United Kingdom: Research Ethics Committee United Kingdom: National Health Service

Keywords provided by NHS Greater Glasgow and Clyde:

acute ischaemic stroke
stroke
thrombolysis
thrombolytic drug therapy

CT perfusion
CT angiography
brain imaging

Additional relevant MeSH terms:

Stroke
Cerebral Infarction
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Brain Infarction
Brain Ischemia

Tissue Plasminogen Activator
Tenecteplase
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Cardiovascular Agents
Therapeutic Uses
Hematologic Agents

ClinicalTrials.gov processed this record on May 16, 2013