None listed
Conditions
Brief summary
A stroke occurs when a clot blocks one of the blood vessels to the brain. This causes poor blood supply and lack of oxygen to the brain tissue. If blood supply is not restored to the brain there is permanent brain damage. Endovascular thrombectomy is an effective treatment to restore blood supply to the brain and reduce disability. However, patients with extensive brain injury due to the stroke can develop brain swelling after restoration of blood flow that increases pressure inside the skull and can cause drowsiness, increased disability and potentially death. This swelling tends to occur over the first 3 days. The aim of this study is to test whether a medication called glibenclamide can reduce this brain swelling and improve outcome after stroke.
Interventions
Intravenous glibenclamide or placebo (8.65 mg total dose administered as a 3-stage continuous infusion over 72 hours):
Day 1 (Hours 0-24)
Participants will receive a Bolus infusion of glibenclamide or placebo (0.13 mg) over 2 minutes followed by an Infusion of 3.04 mg over 6 hr (at a rate of 11.1mL/hr) the infusion rate is decreased to 7.7mL/hr for 18 hrs.
Day 2 (Hours >24-48)
The participants receive glibenclamide or placebo (2.74 mg) for 24 hrs at a rate of 7.7mL/hr.
Day 3 (Hours >48-72)
T
Intravenous glibenclamide or placebo (8.65 mg total dose administered as a 3-stage continuous infusion over 72 hours): Day 1 (Hours 0-24) Participants will receive a Bolus infusion of glibenclamide or placebo (0.13 mg) over 2 minutes followed by an Infusion of 3.04 mg over 6 hr (at a rate of 11.1mL/hr) the infusion rate is decreased to 7.7mL/hr for 18 hrs. Day 2 (Hours >24-48) The participants receive glibenclamide or placebo (2.74 mg) for 24 hrs at a rate of 7.7mL/hr. Day 3 (Hours >48-72) The participants receive glibenclamide or placebo (2.74 mg) for 24 hrs at a rate of 7.7mL/hr. Monitors will visit each site to review pharmacy and medical records to ensure intervention adherence and protocol compliance.
Sponsors
The Florey Institute of Neuroscience and Mental Health
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Patients presenting with acute ischemic stroke due to anterior circulation large vessel occlusion with ability to randomise and commence the investigational product within 10 hours of the time they were last known to be well, or the midpoint of sleep for wakeup stroke. 2. Patient’s age is 18-80 years (inclusive) at the time of informed consent. 3. National Institutes of Health Stroke Scale (NIHSS) 10-25 (inclusive). 4. Commitment to perform EVT, or EVT is underway or completed. 5. Informed consent or emergency treatment approved by ethics committee as per local requirements. Imaging inclusion criteria 6. Arterial occlusion on CTA or MRA of the intracranial internal carotid artery (ICA), or first segment (M1) or dominant second segment (M2) of the middle cerebral artery (MCA). 7. Ischemic core 70-125mL on CT-perfusion or diffusion MRI performed not more than 3 hours prior to randomisation.
Exclusion criteria
1. Brain hemorrhage (other than small petechial/punctate hemorrhages) identified by CT or MRI. 2. Extensive hypodensity on NCCT outside the perfusion lesion that, in the investigator’s opinion, indicates >125mL ischemic core volume. 3. Rapidly improving symptoms that make EVT unlikely to be performed, at the discretion of the investigator. 4. Significant pre-stroke disability: unable to independently perform all duties and activities of daily living without assistance from a caregiver, spouse, or another person. 5. Commitment to immediately perform hemicraniectomy at the time of randomisation. 6. Evidence (clinical or imaging) of concurrent infarction in the contralateral hemisphere deemed by the Investigator to be sufficiently serious so as to affect functional outcome. This would include, for example, a contralateral ACA infarct that leads to bilateral leg paralysis. 7. Clinical signs of herniation, e.g., 1 or 2 fixed, dilated pupils; unconsciousness related to edema (i.e., =2 on item 1a on the NIHSS); and/or loss of other brain stem reflexes, attributable to edema or herniation according to the Investigator’s judgment. 8. NCCT/MRI evidence of anteroseptal/pineal shift >2 mm on the baseline imaging, as assessed by the investigator. 9. The participant is likely to have supportive care withdrawn in the first 3 days, in the judgment of the Investigator. 10. Known allergy to glibenclamide or to another sulfonylurea drug or any of the components of the formulated glibenclamide or matching placebo. 11. Patients who are known to have taken oral glibenclamide within the past 10 hours. 12. Known history of clinically significant severe form of renal or hepatic disorder, in the Investigator's opinion (e.g., dialysis or cirrhosis, respectively). 13. Known history of chronic obstructive pulmonary disease that, in the judgment of the Investigator, is severe (e.g., requiring home oxygen). 14. Known history of clinically significant hypoglycemia, in the Investigator's opinion based on known medical history or local screening laboratory assessments (i.e., screening blood glucose <3.9mmol/L (70 mg/dL). 15. Patients who have or have ever had diabetic ketoacidosis or diabetic coma/precoma. 16. Acute ST elevation myocardial infarction (MI), and/or acute decompensated heart failure, and/or admission for an acute coronary syndrome, MI, cardiac arrest, or non-elective coronary intervention (percutaneous coronary intervention or coronary artery surgery) within the past 3 months. 17. New York Heart Association heart failure III/IV (class III: marked limitation in activity due to symptoms, even during less-thanordinary activity, e.g. walking short distances (20-100 m); class IV: severe limitations. Experiences symptoms even while at rest. Mostly bedbound patients). 18. Patients with known glucose-6-phosphate dehydrogenase (G6PD) enzyme deficiency. 19. Serious local infection (e.g., cellulitis, abscess) or systemic infection (e.g., septicemia) that required hospitalisation or was clinically significant in the opinion of the Investigator within 3 days prior to Screening. 20. Females who are pregnant or women of childbearing potential with a positive pregnancy test at time of admission. 21. Nursing women who are unable to stop breastfeeding during study treatment infusion and for 7 days following the end of study treatment infusion. 22. Known current participation or known history of participation in any other investigational study that involved treatment with an investigational drug within 14 days prior to enrolment. 23. Any terminal illness such that patient would not be expected to survive more than 1 year. 24. Any condition that, in the judgment of the investigator could impose hazards to the patient if study therapy is initiated or affect the participation of the patient in the study.
Outcome results
None listed