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

NCT01472926 | Completed Phase 2 DMC

• 2 other identifiers: 2010-024541-67TSA 2010/04
• Study Type: interventional
• Target: 104
• Locations: 1 country
• Sites: 1

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.

Conditions

Stroke

Keywords

acute ischaemic stroke; stroke; thrombolysis; thrombolytic drug therapy; CT perfusion; CT angiography; brain imaging

Outcome Measures

Primary Outcomes (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.

  48 hours

Secondary Outcomes (9)

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

  48 hours

• Early clinical improvement 24 hours post treatment

  24 hours

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

  48 hours

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

  30 Days

• Distribution of functional outcome scores (mRS) at Day 90

  90 days

Study Arms (2)

Tenecteplase 0.25 mg/kg

EXPERIMENTAL

Intravenous tenecteplase 0.25 mg/kg (single bolus, maximum 25 mg)

Drug: Tenecteplase

Alteplase 0.9 mg/kg

ACTIVE COMPARATOR

Intravenous alteplase 0.9 mg/kg (10% bolus and 90% as IV infusion over 1 hour, maximum 90 mg)

Drug: alteplase

Interventions

Tenecteplase DRUG

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

Also known as: Metalyse, TNK

Tenecteplase 0.25 mg/kg

alteplase DRUG

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

Also known as: Actilyse, recombinant tissue plasminogen activator (rtPA)

Alteplase 0.9 mg/kg

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• NHS Greater Glasgow and Clyde: lead
• University of Glasgow: collaborator

Study Sites (1)

Southern General Hospital

Glasgow, Scotland, G51 4TF, United Kingdom

Location

Related Publications (3)

• 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.

  PMID: 27965285 DERIVED

• 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.

  PMID: 26514192 DERIVED

• 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.

  PMID: 25726502 DERIVED

MeSH Terms

Conditions

Stroke

Interventions

Tenecteplase; Tissue Plasminogen Activator

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Serine Endopeptidases; Endopeptidases; Peptide Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Serine Proteases; Plasminogen Activators; Blood Coagulation Factors; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Biological Factors

Study Officials

• Keith Muir

  The University of Glasgow

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 14, 2011
• First Posted: November 17, 2011
• Study Start: December 1, 2011
• Primary Completion: December 10, 2013
• Study Completion: December 10, 2013
• Last Updated: August 3, 2018

Record last verified: 2012-08

Locations

GB (1)