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

August 1, 2018 updated by: NHS Greater Glasgow and Clyde

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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

Interventional

Enrollment (Actual)

104

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United Kingdom
    • Scotland
      • Glasgow, Scotland, United Kingdom, G51 4TF
        • Southern General Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / 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:
  • TNK
  • Metalyse
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)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
48 hours

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
48 hours
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
24 hours
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
48 hours
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)
30 Days
Distribution of functional outcome scores (mRS) at Day 90
Time Frame: 90 days
Distribution of functional outcome scores (mRS)
90 days
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)
30 days
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)
90 days
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
90 Days
Mortality at Day 90
Time Frame: 90 Days
90 Days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

NHS Greater Glasgow and Clyde

Collaborators

University of Glasgow

Investigators

  • Study Chair: Keith Muir, The University of Glasgow

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 2011

Primary Completion (Actual)

December 10, 2013

Study Completion (Actual)

December 10, 2013

Study Registration Dates

First Submitted

November 14, 2011

First Submitted That Met QC Criteria

November 16, 2011

First Posted (Estimate)

November 17, 2011

Study Record Updates

Last Update Posted (Actual)

August 3, 2018

Last Update Submitted That Met QC Criteria

August 1, 2018

Last Verified

August 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2010-024541-67 (EudraCT Number)
  • TSA 2010/04 (Other Grant/Funding Number: The Stroke Association)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Stroke

Clinical Trials on Tenecteplase

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Egypt

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe