Trial of EXenatide in Acute Ischaemic Stroke

Acute Ischemic Stroke Clinical Trial

— TEXAIS  

Official title:

A Multicentre, Randomised Controlled Trial of Exenatide Versus Standard Care in Acute Ischemic Stroke (TEXAIS)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03287076
• Other study ID #: NTA1127
• Secondary ID: 2018-004325-88
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: November 23, 2017
• Est. completion date: December 31, 2021

Study information

• Verified date: September 2021
• Source: Neuroscience Trials Australia
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 350
• Est. completion date: December 31, 2021
• Est. primary completion date: October 4, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Acute Ischemic Stroke
• Cerebral Infarction
• Ischemia
• Stroke

Intervention

Drug:
• Exenatide Injection
5µg subcutaneously twice daily for five days, commencing within 9 hours of symptom onset

Locations

Country	Name	City	State
Australia	Sunshine Coast University Hospital	Birtinya	Queensland
Australia	Box Hill Hospital	Box Hill	Victoria
Australia	St Vincent's Hospital Sydney	Darlinghurst	New South Wales
Australia	St Vincent's Hospital Melbourne	Fitzroy	Victoria
Australia	Austin Hospital	Heidelberg	Victoria
Australia	Royal Brisbane and Women's Hospital	Herston	Queensland
Australia	Launceston General Hospital	Launceston	Tasmania
Australia	Liverpool Hospital	Liverpool	New South Wales
Australia	Alfred Hospital	Melbourne	Victoria
Australia	St John of God Midland Public & Private Hospital	Midland	Western Australia
Australia	Fiona Stanley Hospital	Murdoch	Western Australia
Australia	Royal Melbourne Hospital	Parkville	Victoria
Australia	Princess Alexandra Hospital	Woolloongabba	Queensland
Finland	Helsinki University Hospital	Helsinki
New Zealand	CDHB Christchurch Hospital	Christchurch

Sponsors (3)

Lead Sponsor	Collaborator
Neuroscience Trials Australia	Monash University, National Health and Medical Research Council, Australia

Countries where clinical trial is conducted

Australia,  Finland,  New Zealand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	improved neurological outcome	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	7 days
Secondary	post stroke hyperglycaemia	reduce the occurrence of post stroke hyperglycaemia (>7mmol/l).	90 days
Secondary	Modified Rankin Scale	improve Modified Rankin Scale (mRS) at 90 days	90 days
Secondary	NIHSS	improve NIHSS at 90 days	90 days