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StrokePhase 2ATTESTNCT01472926

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

A Phase 2 study testing Tenecteplase and alteplase in people with Stroke, run by NHS Greater Glasgow and Clyde at 1 site in United Kingdom.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Stroke
What is being tested?
Tenecteplase and alteplase
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
104 participants
Where
1 siteUnited Kingdom
Study dates
Dec 2011to 10 Dec 2013
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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
Show all 20Show fewer
  • 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

Trial locations and contacts

1 site in 1 country.

United Kingdom1 site

  • Southern General Hospital

    Glasgow, Scotland, G51 4TF

Other trials in United Kingdom

About this study

Official title: 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.

Read the 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.

Conditions
Stroke
Being tested
Tenecteplase, alteplase
Keywords
acute ischaemic stroke, stroke, thrombolysis, thrombolytic drug therapy, CT perfusion, CT angiography, brain imaging
Medical subject headings
Stroke

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TenecteplaseDrug

    Also called Metalyse, TNK

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

  • alteplaseDrug

    Also called Actilyse, recombinant tissue plasminogen activator (rtPA)

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

Study groups in NCT01472926
Study groupRoleWhat they receive
Tenecteplase 0.25 mg/kgExperimentalIntravenous tenecteplase 0.25 mg/kg (single bolus, maximum 25 mg)
Receives: Drug: Tenecteplase
Alteplase 0.9 mg/kgActive comparatorIntravenous alteplase 0.9 mg/kg (10% bolus and 90% as IV infusion over 1 hour, maximum 90 mg)
Receives: Drug: alteplase

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    Percent penumbral salvage at 24-48h (initial CTP-defined penumbra volume versus 24-48h CT infarct volume.

    Measured: 48 hours

Secondary outcomes (9)

  1. Proportion of patients exhibiting recanalisation (on computed tomography angiography, CTA) 24-48 hours post treatment

    Proportion of patients exhibiting recanalisation (measured by CTA) 24-48 hours post treatment

    Measured: 48 hours

  2. Early clinical improvement 24 hours post treatment

    Early clinical improvement (National Institutes of Health Stroke Scale [NIHSS] score reduced by >=4 points, or = 0 or 1) 24 hours post treatment

    Measured: 24 hours

  3. Proportion of patients with symptomatic intracerebral haemorrhage (SICH) on 24-48 hour CT

    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

    Measured: 48 hours

  4. Distribution of functional outcome by modified Rankin Scale (mRS) scores at Day 30

    Distribution of outcome scores on the modified Rankin Scale (mRS)

    Measured: 30 Days

  5. Distribution of functional outcome scores (mRS) at Day 90

    Distribution of functional outcome scores (mRS)

    Measured: 90 days

  6. Proportion of patients with favourable clinical outcome (mRS 0-1) at Day 30

    Proportion of patients with favourable clinical outcome (mRS 0-1)

    Measured: 30 days

  7. Proportion of patients with favourable clinical outcome (mRS 0-1) at Day 90

    Proportion of patients with favourable clinical outcome (mRS 0-1)

    Measured: 90 days

  8. Average 'home time' by day 90

    Average 'home time' (number of nights spent in non-institutional private residence) by Day 90

    Measured: 90 Days

  9. Mortality at Day 90

    Measured: 90 Days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Nov 2011 (estimated)
  2. Study startDec 2011
  3. Primary completion10 Dec 2013
  4. Study completion10 Dec 2013

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Single blind
Who is masked
Outcomes assessor
Enrolment
104 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01472926
Sponsor's protocol ID
2010-024541-67
Other IDs
TSA 2010/04, 2010-024541-67
Acronym
ATTEST
Status last verified
Aug 2012
First submitted
14 Nov 2011
Last updated
3 Aug 2018
Results posted
No
Data monitoring committee
Yes

Publications

  • Bivard A, Huang X, McElduff P, Levi CR, Campbell BC, Cheripelli BK, Kalladka D, Moreton FC, Ford I, Bladin CF, Davis SM, Donnan GA, Muir KW, Parsons MW. Impact of Computed Tomography Perfusion Imaging on the Response to Tenecteplase in Ischemic Stroke: Analysis of 2 Randomized Controlled Trials. Circulation. 2017 Jan 31;135(5):440-448. doi: 10.1161/CIRCULATIONAHA.116.022582. Epub 2016 Dec 13.

    PubMed 27965285

  • Huang X, Moreton FC, Kalladka D, Cheripelli BK, MacIsaac R, Tait RC, Muir KW. Coagulation and Fibrinolytic Activity of Tenecteplase and Alteplase in Acute Ischemic Stroke. Stroke. 2015 Dec;46(12):3543-6. doi: 10.1161/STROKEAHA.115.011290. Epub 2015 Oct 29.

    PubMed 26514192

  • Huang X, Cheripelli BK, Lloyd SM, Kalladka D, Moreton FC, Siddiqui A, Ford I, Muir KW. Alteplase versus tenecteplase for thrombolysis after ischaemic stroke (ATTEST): a phase 2, randomised, open-label, blinded endpoint study. Lancet Neurol. 2015 Apr;14(4):368-76. doi: 10.1016/S1474-4422(15)70017-7. Epub 2015 Feb 26.

    PubMed 25726502

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Tenecteplase and alteplase in people with Stroke, run by NHS Greater Glasgow and Clyde at 1 site in United Kingdom.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 3 Aug 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01472926, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Aug 2018.

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