Alteplase-Tenecteplase Trial Evaluation for Stroke Thrombolysis

NCT02814409 | Completed Phase 3 DMC

• 1 other identifier: GN14NE598
• Study Type: interventional
• Target: 1,858
• Locations: 1 country
• Sites: 1

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?

Conditions

Ischemic Stroke

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• 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 Outcomes (6)

• 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

Study Arms (2)

Alteplase - standard care

ACTIVE COMPARATOR

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

Tenecteplase

EXPERIMENTAL

Tenecteplase 0.25mg/kg administered as a single rapid intravenous bolus (maximum dose 25mg).

Drug: Intravenous Tenecteplase

Interventions

Intravenous recombinant tissue plasminogen activator (rtPA) Alteplase DRUG

IV Alteplase 0.9mg/kg (max 90mg) bolus + 1h infusion

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

Alteplase - standard care

Intravenous Tenecteplase DRUG

IV Tenecteplase 0.25mg/kg (max 25mg) single bolus

Also known as: Metalyse, TNK

Tenecteplase

Eligibility Criteria

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

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• NHS Greater Glasgow and Clyde: lead
• University of Glasgow: collaborator
• University of Edinburgh: collaborator
• Oxford University Hospitals NHS Trust: collaborator

Study Sites (1)

Queen Elizabeth University Hospital

Glasgow, United Kingdom

Location

Related Publications (1)

• Muir KW, Ford GA, Ford I, Wardlaw JM, McConnachie A, Greenlaw N, Mair G, Sprigg N, Price CI, MacLeod MJ, Dima S, Venter M, Zhang L, O'Brien E, Sanyal R, Reid J, Sztriha LK, Haider S, Whiteley WN, Kennedy J, Perry R, Lakshmanan S, Chakrabarti A, Hassan A, Marigold R, Raghunathan S, Sims D, Bhandari M, Wiggam I, Rashed K, Douglass C; ATTEST-2 Investigators. Tenecteplase versus alteplase for acute stroke within 4.5 h of onset (ATTEST-2): a randomised, parallel group, open-label trial. Lancet Neurol. 2024 Nov;23(11):1087-1096. doi: 10.1016/S1474-4422(24)00377-6.

  PMID: 39424558 DERIVED

MeSH Terms

Conditions

Ischemic Stroke

Interventions

Tissue Plasminogen Activator; Tenecteplase

Condition Hierarchy (Ancestors)

Stroke; 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, MD, FRCP

  University of Glasgow

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 23, 2016
• First Posted: June 27, 2016
• Study Start: December 15, 2016
• Primary Completion: August 31, 2023
• Study Completion: January 10, 2024
• Last Updated: June 13, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)