Alteplase-Tenecteplase Trial Evaluation for Stroke Thrombolysis (ATTEST2)

• ClinicalTrials.gov Identifier: NCT02814409
• Recruitment Status: Recruiting
• First Posted: June 27, 2016
• Last Update Posted: March 29, 2018
• Sponsor: NHS Greater Glasgow and Clyde
• Collaborators: University of Glasgow; University of Edinburgh; Oxford University Hospitals NHS Trust
• Information provided by (Responsible Party): NHS Greater Glasgow and Clyde

Study Description

Brief Summary:

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?

Condition or disease	Intervention/treatment	Phase
Ischemic Stroke	Drug: Intravenous recombinant tissue plasminogen activator (rtPA) Alteplase; Drug: Intravenous Tenecteplase	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 1870 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Alteplase-Tenecteplase Trial Evaluation for Stroke Thrombolysis (ATTEST 2)
• Actual Study Start Date: December 15, 2016
• Estimated Primary Completion Date: August 2019
• Estimated Study Completion Date: August 2019

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. modified Rankin Scale [ Time Frame: Day 90 (+/- 7) ]
   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.

Secondary Outcome Measures :

1. Full neurological recovery (modified Rankin Scale 0-1 versus 2-6). [ Time Frame: Day 90 (+/- 7) ]
2. Independent recovery (modified Rankin Scale score 0-2 versus 3-6). [ Time Frame: Day 90 (+/- 7) ]
3. 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). [ Time Frame: 24 hours ]
4. Health Related Quality of Life (EuroQol five dimensions questionnaire, EQ-5D) [ Time Frame: Day 90 (+/- 7) ]
5. Barthel Index score [ Time Frame: Day 90 (+/- 7) ]

Other Outcome Measures:

1. Mortality [ Time Frame: Day 90 (+/- 7) ]
2. 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). [ Time Frame: 36 hours ]
3. Symptomatic Intra-Cerebral Haemorrhage (SICH) by (European Cooperative Acute Stroke Study) ECASS-2 and ECASS-3 definitions. [ Time Frame: up to day 90 ]
4. Parenchymal Haematoma type 2 (PH2) haemorrhage on post-treatment computerised tomography (CT) scan up to 36 hours after treatment. [ Time Frame: 36 hours ]
5. Intracranial haemorrhage [ Time Frame: 22-36 hours ]
   Any intracranial haemorrhage on 22-36 hours computerised tomography (CT) scan
6. Significant extracranial haemorrhage (requirement for blood transfusion or drop in haemoglobin of ≥20mg/l in the 36h after treatment). [ Time Frame: 36 hours ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Contacts

Contact: Alicia Murray, BSc, PhD; Alicia.Murray@glasgow.ac.uk

Locations

United Kingdom

Queen Elizabeth University Hospital; Recruiting

Glasgow, United Kingdom

Contact: Alicia Murray alicia.murray@glasgow.ac.uk

Sponsors and Collaborators

NHS Greater Glasgow and Clyde

University of Glasgow

University of Edinburgh

Oxford University Hospitals NHS Trust

Investigators

• Principal Investigator: Keith Muir, MD, FRCP; University of Glasgow

More Information

• Responsible Party: NHS Greater Glasgow and Clyde
• ClinicalTrials.gov Identifier: NCT02814409 History of Changes
• Other Study ID Numbers: NorthGlasgowU
• First Posted: June 27, 2016
• Last Update Posted: March 29, 2018
• Last Verified: March 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Additional relevant MeSH terms:

Stroke; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Tissue Plasminogen Activator; Plasminogen; Tenecteplase; Fibrinolytic Agents; Fibrin Modulating Agents; Molecular Mechanisms of Pharmacological Action