Alteplase-Tenecteplase Trial Evaluation for Stroke Thrombolysis (ATTEST2)

Alteplase-Tenecteplase Trial Evaluation for Stroke Thrombolysis (ATTEST 2)

The principle research question is: in patients with acute ischaemic stroke eligible for intravenous (IV) thrombolysis, is tenecteplase superior in efficacy to alteplase, based on functional outcome as assessed by modified Rankin Scale distribution at day 90?

Study Overview

• Status: Unknown
• Conditions: Ischemic Stroke
• Intervention / Treatment: Drug: Intravenous recombinant tissue plasminogen activator (rtPA) Alteplase; Drug: Intravenous Tenecteplase

• Study Type: Interventional
• Enrollment (Anticipated): 1870
• Phase: Phase 3

Contacts and Locations

Study Locations

• United Kingdom
  • Glasgow, United Kingdom
    • Recruiting
    • Queen Elizabeth University Hospital
    • Contact: Alicia Murray; Email: Alicia.Murray@glasgow.ac.uk

Participation Criteria

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:

• Eligible for intravenous thrombolysis.
• Male or non-pregnant female ≥18 years of age.
• <4.5h after symptom onset.
• Consent of patient or legal representative.
• Independent prior to the stroke (estimated modified Rankin Scale 0-1).

Exclusion criteria:

• Eligible for intravenous thrombolysis: Evidence of intracranial haemorrhage or significant non-stroke intracranial pathology likely to account for clinical presentation or represent a risk of intracerebral haemorrhage (eg Central Nervous System neoplasm) on pre-treatment computerised tomography (CT) scan; Stroke within the previous 14 days, thrombolytic therapy within the past 14 days, or hypodensity on pre-treatment computerised tomography (CT) scan consistent with recent cerebral ischaemia other than the presenting event; Systolic blood pressure more than 185 or diastolic blood pressure more than 110 mmHg, or aggressive management (intravenous pharmacotherapy) necessary to reduce blood pressure to these limits; Clinical history suggestive of subarachnoid haemorrhage even if no blood is evident on computerised tomography (CT) scan; High risk of haemorrhage, including major surgery, trauma or gastrointestinal or urinary tract haemorrhage within the previous 21 days; Arterial puncture at a non-compressible site within the previous 7 days; Prolonged cardiopulmonary resuscitation (> 2 minutes) within the previous 14 days; 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; Known history of haemorrhagic stroke; Known defect of clotting or platelet function (other than antiplatelet therapy); Hypo- or hyperglycaemia (blood glucose <2 mmol/l or >18 mmol/l) sufficient to account for neurological symptoms; Seizure at onset of symptoms unless brain imaging identifies positive evidence of significant brain ischaemia (eg early ischaemic change or hyperdense vessel on plain computerised tomography (CT) scan, computerised tomography angiography (CTA) scan confirmed arterial occlusion); Pregnancy (for women of child-bearing potential a negative pregnancy test will be required prior to randomisation); Inadequate haemostasis: Taking warfarin and international normalised ratio (INR) >1.3, Taking a Direct Oral Anticoagulant (dabigatran, rivaroxaban, apixaban, edoxaban) unless known to be >12 hours since last dose and with normal coagulation assays, Low molecular weight heparin (at doses other than prophylaxis of venous thromboembolism) administered within the preceding 48 hours, Unfractionated heparin administered within the previous 48 hours and activated partial thromboplastin time (APTT) is prolonged.
• Acute endovascular treatment for stroke planned.
• Any major medical condition likely to limit survival to day 90.
• Unavailable for day 90 follow-up.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Alteplase - standard care; Alteplase 0.9 mg/kg with 10% of the total dose administered as an initial intravenous bolus and remaining 90% of the total dose administered as an intravenous infusion over 1 hour (maximum dose 90mg).	Drug: Intravenous recombinant tissue plasminogen activator (rtPA) Alteplase
Experimental: Tenecteplase; Tenecteplase 0.25mg/kg administered as a single rapid intravenous bolus (maximum dose 25mg).	Drug: Intravenous Tenecteplase

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
modified Rankin Scale	modified Rankin Scale (mRS) at day 90, determined by the Rankin Focused Assessment (RFA) method using centralised telephone interview, analysed by ordinal distribution ("shift") analysis of the scores in intervention and control groups.	Day 90 (+/- 7)

Secondary Outcome Measures

Outcome Measure	Time Frame
Full neurological recovery (modified Rankin Scale 0-1 versus 2-6).	Day 90 (+/- 7)
Independent recovery (modified Rankin Scale score 0-2 versus 3-6).	Day 90 (+/- 7)
Early major neurological improvement of 8 or more points, or return to the National Institutes of Health Stroke Scale (NIHSS) total score of 0 or 1 at 24 hour(s).	24 hours
Health Related Quality of Life (EuroQol five dimensions questionnaire, EQ-5D)	Day 90 (+/- 7)
Barthel Index score	Day 90 (+/- 7)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mortality		Day 90 (+/- 7)
Imaging scan up to 36 hours, combined with a neurological deterioration NIHSS≥4 points from baseline (or lowest NIHSS value baseline-24 h), or leading to death (Safe Implementation of Thrombolysis in Stroke-Monitoring study definition).		36 hours
Symptomatic Intra-Cerebral Haemorrhage (SICH) by (European Cooperative Acute Stroke Study) ECASS-2 and ECASS-3 definitions.		up to day 90
Parenchymal Haematoma type 2 (PH2) haemorrhage on post-treatment computerised tomography (CT) scan up to 36 hours after treatment.		36 hours
Intracranial haemorrhage	Any intracranial haemorrhage on 22-36 hours computerised tomography (CT) scan	22-36 hours
Significant extracranial haemorrhage (requirement for blood transfusion or drop in haemoglobin of ≥20mg/l in the 36h after treatment).		36 hours

Collaborators and Investigators

• Sponsor: NHS Greater Glasgow and Clyde
• Collaborators: University of Edinburgh; Oxford University Hospitals NHS Trust; University of Glasgow
• Investigators: Principal Investigator: Keith Muir, MD, FRCP, University of Glasgow

Study record dates

Study Major Dates

• Study Start (Actual): December 15, 2016
• Primary Completion (Anticipated): August 1, 2019
• Study Completion (Anticipated): August 1, 2019

Study Registration Dates

• First Submitted: June 23, 2016
• First Submitted That Met QC Criteria: June 23, 2016
• First Posted (Estimate): June 27, 2016

Study Record Updates

• Last Update Posted (Actual): March 29, 2018
• Last Update Submitted That Met QC Criteria: March 27, 2018
• Last Verified: March 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Stroke; Ischemic Stroke; Molecular Mechanisms of Pharmacological Action; Fibrinolytic Agents; Fibrin Modulating Agents; Tissue Plasminogen Activator; Plasminogen; Tenecteplase
• Other Study ID Numbers: NorthGlasgowU

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No