TEXAIS: Trial of EXenatide in Acute Ischaemic Stroke

Sponsor
Neuroscience Trials Australia (Other)
Overall Status
Active, not recruiting
CT.gov ID
NCT03287076
Collaborator
National Health and Medical Research Council, Australia (Other), Monash University (Other)
350
15
2
49.2
23.3
0.5

Study Details

Study Description

Brief Summary

A multicentre, randomised controlled Trial of Exenatide versus standard care in Acute Ischemic Stroke

Condition or Disease Intervention/Treatment Phase
  • Drug: Exenatide Injection
Phase 2

Detailed Description

Overview: Elevated blood glucose levels are common in many acute diseases, resulting in worse clinical outcomes. Hyperglycaemia in acute ischaemic stroke (post-stroke hyperglycaemia [PSH]) occurs in up to 50% patients, reduces the efficacy of stroke thrombolysis with increased risk of haemorrhage, increases infarct size, and results in worse clinical outcomes and death. Insulin-based therapies have not proved beneficial in treating PSH: they are difficult to implement and maintain, cause frequent hypoglycaemia, may cause increased infarct size, and do not reduce mortality or improve clinical outcomes. An alternative, simple to use, treatment for PSH may therefore have a significant impact not only for acute stroke care, but in other acute diseases.

Pilot data: Exenatide is a commonly used diabetes drug (a synthetic glucagon- like peptide-1 receptor agonist) that increases insulin secretion. Importantly, this action is glucose dependent - as blood glucose levels decrease, its stimulatory effect on insulin secretion subsides, with a very low risk of hypoglycaemia. A small randomised pilot study of 17 consecutive, unselected patients (ie. regardless of their admission glucose level) with acute ischaemic stroke compared subcutaneous exenatide 5μg for 5 days with routine standard of care. Overall, blood glucose levels remained consistently lower (and less variable) in the exenatide group, and most noticeably in those stroke patients with known diabetes. Exenatide was safe and well tolerated by all patients, with no symptomatic hypoglycaemia.

Trial design: TEXAIS is a 3 year Phase 2, multi centre, prospective, randomised, open label, blinded end-point (PROBE) trial comparing Exenatide to Standard of Care. The sample size is 528 patients (264 in each arm).

Intervention: Treatment arm will receive Exenatide (Byetta) 5μg subcutaneously twice daily for five days, commencing within 9 hours of symptom onset. Stroke onset time for wake-up strokes is taken as mid-point between going to bed, and waking up. Antiemetic therapy (metoclopramide or ondansetron) will be commenced with the first dose of Exenatide. In patients receiving tPA, Exenatide will be given alongside, or as soon as possible, following tPA administration (within 60 minutes). Diabetic patients already on oral agents and/or insulin may continue these (as per standard practice) in addition to Exenatide. Continuous glucose monitors (CGMs) will track the intra-day dynamic variability of glucose in acute stroke.

Translation: TEXAIS is a simple, practical, study that can enrol all patients with ischaemic stroke, regardless of admission blood glucose level, regardless of stroke severity, with no target glucose level, and with low risk of hypoglycaemia.

Study Design

Study Type:
Interventional
Actual Enrollment :
350 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Single (Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Multicentre, Randomised Controlled Trial of Exenatide Versus Standard Care in Acute Ischemic Stroke (TEXAIS)
Actual Study Start Date :
Nov 23, 2017
Anticipated Primary Completion Date :
Oct 4, 2021
Anticipated Study Completion Date :
Dec 31, 2021

Arms and Interventions

Arm Intervention/Treatment
Experimental: Active

Patients will receive exenatide injections

Drug: Exenatide Injection
5μg subcutaneously twice daily for five days, commencing within 9 hours of symptom onset
Other Names:
  • Byetta
  • No Intervention: Standard Care

    Standard care for stroke as per hospital protocol

    Outcome Measures

    Primary Outcome Measures

    1. improved neurological outcome [7 days]

      Treatment with short acting Exenatide (Byetta) in patients with acute ischaemic stroke is hypothesised to improve neurological outcome as measured by ≥8 point improvement in the National Institutes of Health Stroke Scale (NIHSS) stroke disability score (or NIHSS 0-1) at 7 days

    Secondary Outcome Measures

    1. post stroke hyperglycaemia [90 days]

      reduce the occurrence of post stroke hyperglycaemia (>7mmol/l).

    2. Modified Rankin Scale [90 days]

      improve Modified Rankin Scale (mRS) at 90 days

    3. NIHSS [90 days]

      improve NIHSS at 90 days

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Males and females 18 years or older

    • Acute Ischaemic Stroke - CT brain exclusion of haemorrhagic stroke

    • Blood glucose level on admission ≥ 4mmol/L

    • First trial treatment possible within 9 hours of stroke onset

    • Pre-morbid /mRS score of 0-2

    Exclusion Criteria:
    • Haemorrhagic stroke

    • Poor clinical prognosis /palliation (considered unlikely to survive beyond 14 days post stroke).

    • Any known allergy or hypersensitivity to Exenatide

    • Females who are pregnant (known or suspected) or currently breastfeeding

    • Any past history of pancreatitis or evidence of active pancreatitis

    • History of active severe gastrointestinal disease (including but not limited to gastroparesis and dumping syndrome)

    • Current chronic kidney disease stage 4 or 5 (creatinine clearance <30ml/min)

    • Current participation in another interventional clinical trial

    • Inability to provide consent (participant or person responsible as local laws apply)

    • Current use of Exenatide (Byetta®), or other GLP-1 agonist diabetes medication

    • Patients considered unlikely to be able to be followed up at 3 months (including but not limited to geographical location of patient at 3 months)

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 St Vincent's Hospital Sydney Darlinghurst New South Wales Australia 2010
    2 Liverpool Hospital Liverpool New South Wales Australia 2170
    3 Sunshine Coast University Hospital Birtinya Queensland Australia 4575
    4 Royal Brisbane and Women's Hospital Herston Queensland Australia 4029
    5 Princess Alexandra Hospital Woolloongabba Queensland Australia 4102
    6 Launceston General Hospital Launceston Tasmania Australia 7250
    7 Box Hill Hospital Box Hill Victoria Australia 3128
    8 St Vincent's Hospital Melbourne Fitzroy Victoria Australia 3065
    9 Austin Hospital Heidelberg Victoria Australia 3084
    10 Alfred Hospital Melbourne Victoria Australia 3004
    11 Royal Melbourne Hospital Parkville Victoria Australia 3050
    12 St John of God Midland Public & Private Hospital Midland Western Australia Australia 6056
    13 Fiona Stanley Hospital Murdoch Western Australia Australia 6150
    14 Helsinki University Hospital Helsinki Finland 00290
    15 CDHB Christchurch Hospital Christchurch New Zealand 8140

    Sponsors and Collaborators

    • Neuroscience Trials Australia
    • National Health and Medical Research Council, Australia
    • Monash University

    Investigators

    • Principal Investigator: Christopher Bladin, The Florey Institute of Neuroscience & Mental Health Melbourne Brain Centre

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Neuroscience Trials Australia
    ClinicalTrials.gov Identifier:
    NCT03287076
    Other Study ID Numbers:
    • NTA1127
    • 2018-004325-88
    First Posted:
    Sep 19, 2017
    Last Update Posted:
    Sep 14, 2021
    Last Verified:
    Sep 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Product Manufactured in and Exported from the U.S.:
    Yes
    Keywords provided by Neuroscience Trials Australia
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Sep 14, 2021