Alteplase-Tenecteplase Trial Evaluation for Stroke Thrombolysis

Ischemic Stroke Clinical Trial

— ATTEST2  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02814409
• Other study ID #: GN14NE598
• Status: Completed
• Phase: Phase 3
• Start date: December 15, 2016
• Est. completion date: January 10, 2024

Study information

• Verified date: June 2024
• Source: NHS Greater Glasgow and Clyde
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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?

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1858
• Est. completion date: January 10, 2024
• Est. primary completion date: August 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 0-2).

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.

• Any major medical condition likely to limit survival to day 90.

• Unavailable for day 90 follow-up.

Related Conditions & MeSH terms

• Ischemic Stroke
• Stroke

Intervention

Drug:
• Intravenous recombinant tissue plasminogen activator (rtPA) Alteplase
IV Alteplase 0.9mg/kg (max 90mg) bolus + 1h infusion
• Intravenous Tenecteplase
IV Tenecteplase 0.25mg/kg (max 25mg) single bolus

Locations

Country	Name	City	State
United Kingdom	Queen Elizabeth University Hospital	Glasgow

Sponsors (4)

Lead Sponsor	Collaborator
NHS Greater Glasgow and Clyde	Oxford University Hospitals NHS Trust, University of Edinburgh, University of Glasgow

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Mortality	Mortality	Day 90 (+/- 7)
Other	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).	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
Other	Symptomatic Intra-Cerebral Haemorrhage (SICH) by (European Cooperative Acute Stroke Study) ECASS-2 and ECASS-3 definitions.	Symptomatic Intra-Cerebral Haemorrhage (SICH) by (European Cooperative Acute Stroke	up to day 90
Other	Parenchymal Haematoma type 2 (PH2) haemorrhage on post-treatment computerised tomography (CT) scan up to 36 hours after treatment.	Parenchymal Haematoma type 2 (PH2) haemorrhage on post-treatment computerised	36 hours
Other	Intracranial haemorrhage	Any intracranial haemorrhage on 22-36 hours computerised tomography (CT) scan	22-36 hours
Other	Significant extracranial haemorrhage (requirement for blood transfusion or drop in haemoglobin of =20mg/l in the 36h after treatment).	Significant extracranial haemorrhage (requirement for blood transfusion or drop in haemoglobin of =20mg/l in the 36h after treatment).	36 hours
Primary	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	Full neurological recovery (modified Rankin Scale 0-1 versus 2-6).	Full neurological recovery (modified Rankin Scale 0-1 versus 2-6).	Day 90 (+/- 7)
Secondary	Independent recovery (modified Rankin Scale score 0-2 versus 3-6).	Independent recovery (modified Rankin Scale score 0-2 versus 3-6).	Day 90 (+/- 7)
Secondary	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).	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
Secondary	Health Related Quality of Life (EuroQol five dimensions questionnaire, EQ-5D)	Health Related Quality of Life (EuroQol five dimensions questionnaire, EQ-5D)	Day 90 (+/- 7)
Secondary	Barthel Index score	Barthel Index score	Day 90 (+/- 7)
Secondary	Need for thrombectomy	Need for thrombectomy	24 hours