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

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2012 by NHS Greater Glasgow and Clyde
Sponsor:
Collaborator:
University of Glasgow
Information provided by (Responsible Party):
Keith Muir, NHS Greater Glasgow and Clyde
ClinicalTrials.gov Identifier:
NCT01472926
First received: November 14, 2011
Last updated: August 9, 2012
Last verified: August 2012
  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:


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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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 August 01, 2014