Clinical trial NCT03287076: Trial of EXenatide in Acute Ischaemic Stroke
Official title: A Multicentre, Randomised Controlled Trial of Exenatide Versus Standard Care in Acute Ischemic Stroke (TEXAIS)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Acute Ischemic Stroke
Keywords: stroke
glucose
exenatide
Lead sponsor: Neuroscience Trials Australia
Sponsor class: OTHER
Collaborators: name: National Health and Medical Research Council, Australia
name: Monash University
First posted: 2017-09-19
Enrollment: 350
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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.

Eligibility criteria: 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)

Primary outcomes:
measure: improved neurological outcome
timeFrame: 7 days
Secondary outcomes:
measure: post stroke hyperglycaemia
timeFrame: 90 days
measure: Modified Rankin Scale
timeFrame: 90 days
measure: NIHSS
timeFrame: 90 days
Other outcomes:
Locations:
city: Darlinghurst
country: Australia
facility: St Vincent's Hospital Sydney
state: New South Wales
city: Liverpool
country: Australia
facility: Liverpool Hospital
state: New South Wales
city: Birtinya
country: Australia
facility: Sunshine Coast University Hospital
state: Queensland
city: Herston
country: Australia
facility: Royal Brisbane and Women's Hospital
state: Queensland
city: Woolloongabba
country: Australia
facility: Princess Alexandra Hospital
state: Queensland
city: Launceston
country: Australia
facility: Launceston General Hospital
state: Tasmania
city: Box Hill
country: Australia
facility: Box Hill Hospital
state: Victoria
city: Fitzroy
country: Australia
facility: St Vincent's Hospital Melbourne
state: Victoria
city: Heidelberg
country: Australia
facility: Austin Hospital
state: Victoria
city: Melbourne
country: Australia
facility: Alfred Hospital
state: Victoria
city: Parkville
country: Australia
facility: Royal Melbourne Hospital
state: Victoria
city: Midland
country: Australia
facility: St John of God Midland Public & Private Hospital
state: Western Australia
city: Murdoch
country: Australia
facility: Fiona Stanley Hospital
state: Western Australia
city: Helsinki
country: Finland
facility: Helsinki University Hospital
city: Christchurch
country: New Zealand
facility: CDHB Christchurch Hospital
Study officials:
affiliation: The Florey Institute of Neuroscience & Mental Health Melbourne Brain Centre
name: Christopher Bladin
role: PRINCIPAL_INVESTIGATOR
References: