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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01472926
Recruitment Status : Completed
First Posted : November 17, 2011
Last Update Posted : August 3, 2018
Sponsor:
Collaborator:
University of Glasgow
Information provided by (Responsible Party):
NHS Greater Glasgow and Clyde

Tracking Information
First Submitted Date  ICMJE November 14, 2011
First Posted Date  ICMJE November 17, 2011
Last Update Posted Date August 3, 2018
Study Start Date  ICMJE December 2011
Actual Primary Completion Date December 10, 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 17, 2011)
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.
Original Primary Outcome Measures  ICMJE
 (submitted: November 16, 2011)
Percent penumbral salvage at 24-48h (initial CTP-defined penumbra volume 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.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 17, 2011)
  • Proportion of patients exhibiting recanalisation (on computed tomography angiography, CTA) 24-48 hours post treatment [ Time Frame: 48 hours ]
    Proportion of patients exhibiting recanalisation (measured by CTA) 24-48 hours post treatment
  • Early clinical improvement 24 hours post treatment [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 30 Days ]
    Distribution of outcome scores on the modified Rankin Scale (mRS)
  • Distribution of functional outcome scores (mRS) at Day 90 [ Time Frame: 90 days ]
    Distribution of functional outcome scores (mRS)
  • Proportion of patients with favourable clinical outcome (mRS 0-1) at Day 30 [ Time Frame: 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 [ Time Frame: 90 days ]
    Proportion of patients with favourable clinical outcome (mRS 0-1)
  • Average 'home time' by day 90 [ Time Frame: 90 Days ]
    Average 'home time' (number of nights spent in non-institutional private residence) by Day 90
  • Mortality at Day 90 [ Time Frame: 90 Days ]
Original Secondary Outcome Measures  ICMJE
 (submitted: November 16, 2011)
  • Proportion of patients exhibiting recanalisation (measured by CTA) 24-48 hours post treatment [ Time Frame: 48 hours ]
    Proportion of patients exhibiting recanalisation (measured by CTA) 24-48 hours post treatment
  • Early clinical improvement 24 hours post treatment [ Time Frame: 24 hours ]
    Early clinical improvement (NIHSS score reduced by 3-4 points, or 0 or 1) 24 hours post treatment
  • Proportion of patients with symptomatic ICH (SICH) on 24-48 hour CT [ Time Frame: 48 hours ]
    Proportion of patients with symptomatic ICH (SICH) on 24-48 hour CT:
    • SITS-MOST definition - PH2/PHr2 + NIHSS deterioration by 3-4 points at 24 hours
    • Any ICH
  • Distribution of functional outcome scores (mRS) at Day 30 [ Time Frame: 30 Days ]
    Distribution of functional outcome scores (mRS)
  • Distribution of functional outcome scores (mRS) at Day 90 [ Time Frame: 90 days ]
    Distribution of functional outcome scores (mRS)
  • Proportion of patients with favourable clinical outcome (mRS 0-1) at Day 30 [ Time Frame: 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 [ Time Frame: 90 days ]
    Proportion of patients with favourable clinical outcome (mRS 0-1)
  • Average 'home time' by day 90 [ Time Frame: 90 Days ]
    Average 'home time' (number of nights spent in non-institutional private residence) by Day 90
  • Mortality at Day 90 [ Time Frame: 90 Days ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Alteplase-Tenecteplase Trial Evaluation for Stroke Thrombolysis- (ATTEST)
Official Title  ICMJE Alteplase-Tenecteplase Trial Evaluation for Stroke Thrombolysis - Pilot Phase (ATTEST)
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Stroke
Intervention  ICMJE
  • Drug: Tenecteplase
    Intravenous (IV) tenecteplase 0.25 mg/kg (single bolus; maximum dose 25 mg)
    Other Names:
    • Metalyse
    • TNK
  • 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)
Study Arms  ICMJE
  • Experimental: Tenecteplase 0.25 mg/kg
    Intravenous tenecteplase 0.25 mg/kg (single bolus, maximum 25 mg)
    Intervention: Drug: Tenecteplase
  • 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)
    Intervention: Drug: alteplase
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: November 16, 2011)
104
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE December 10, 2013
Actual Primary Completion Date December 10, 2013   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01472926
Other Study ID Numbers  ICMJE 2010-024541-67
TSA 2010/04 ( Other Grant/Funding Number: The Stroke Association )
2010-024541-67 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party NHS Greater Glasgow and Clyde
Study Sponsor  ICMJE NHS Greater Glasgow and Clyde
Collaborators  ICMJE University of Glasgow
Investigators  ICMJE
Study Chair: Keith Muir The University of Glasgow
PRS Account NHS Greater Glasgow and Clyde
Verification Date August 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP