title: Pilot study of intravenous glyburide in patients with a large ischemic stroke.
abstract: OBJECTIVE
  Preclinical and retrospective clinical data indicate that glyburide, a selective inhibitor of sulfonylurea receptor 1-transient receptor potential melastatin 4, is effective in preventing edema and improving outcome after focal ischemia. We assessed the feasibility of recruiting and treating patients with severe stroke while obtaining preliminary information on the safety and tolerability of RP-1127 (glyburide for injection).
  
  
  METHODS
  We studied 10 patients with acute ischemic stroke, with baseline diffusion-weighted imaging lesion volumes of 82 to 210 cm3, whether treated with intravenous recombinant tissue-type plasminogen activator, age 18 to 80 years, and time to RP-1127≤10 hours.
  
  
  RESULTS
  Recruitment was completed within 10 months. The mean age was 50.5 years, and baseline diffusion-weighted image lesion volume was 102±23 cm3. There were no serious adverse events related to drug and no symptomatic hypoglycemia. The increase in ipsilateral hemisphere volume was 50±33 cm3. The proportion of 90-day modified Rankin Scale≤4 was 90% (40% modified Rankin Scale, ≤3).
  
  
  CONCLUSIONS
  RP-1127 at a dose of 3 mg/d was well tolerated and did not require any dose reductions. A clinical trial of RP-1127 is feasible.
  
  
  BACKGROUND
  URL: http://www.clinicaltrials.gov. Unique identifier: NCT01268683.
authors.affiliation: From the Division of Neurocritical Care and Emergency Neurology, Department of Neurology, Yale University School of Medicine, New Haven, CT (K.N.S.); Division of Neurocritical Care and Emergency Neurology, Department of Neurology (W.T.K.) and Division of Neuroradiology, Department of Radiology (A.J.Y.), Massachusetts General Hospital, Boston; Department of Public Health Services, Medical University of South Carolina, Charleston (J.J.E.); Department of Neurology, Michael E. DeBakey VA Medical, Baylor College of Medicine, Houston, TX (T.A.K., P.M.); Department of Neurology, Klinik und Poliklinik für Neurologie, Kopf-und Neurozentrum, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany (G.T.); Department of Neurology, Melbourne Brain Centre at the Royal Melbourne Hospital, University of Melbourne, Parkville, Australia (B.C., G.A.D., S.M.D.); Department of Neurology, Stanford University School of Medicine, CA (G.W.A.); Remedy Pharmaceuticals, Inc, New York, NY (S.J.); and Departments of Neurosurgery (J.M.S.) and Neurology (B.J.S.), University of Maryland School of Medicine, Baltimore.
authors.forename: Kevin N
authors.initials: KN
authors.lastname: Sheth
authors.forename: W Taylor
authors.initials: WT
authors.lastname: Kimberly
authors.forename: Jordan J
authors.initials: JJ
authors.lastname: Elm
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Kent
authors.forename: Pitchaiah
authors.initials: P
authors.lastname: Mandava
authors.forename: Albert J
authors.initials: AJ
authors.lastname: Yoo
authors.forename: Götz
authors.initials: G
authors.lastname: Thomalla
authors.forename: Bruce
authors.initials: B
authors.lastname: Campbell
authors.forename: Geoffrey A
authors.initials: GA
authors.lastname: Donnan
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Davis
authors.forename: Gregory W
authors.initials: GW
authors.lastname: Albers
authors.forename: Sven
authors.initials: S
authors.lastname: Jacobson
authors.forename: J Marc
authors.initials: JM
authors.lastname: Simard
authors.forename: Barney J
authors.initials: BJ
authors.lastname: Stern
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001786:Blood Glucose / Q000378:metabolism; D001929:Brain Edema / Q000188:drug therapy / Q000209:etiology; D002545:Brain Ischemia / Q000188:drug therapy*; D015897:Comorbidity; D005260:Female; D005343:Fibrinolytic Agents / Q000627:therapeutic use; D005905:Glyburide / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D007275:Injections, Intravenous; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D061214:Patient Safety; D010865:Pilot Projects; D011446:Prospective Studies; D020521:Stroke / Q000188:drug therapy*; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use; D016896:Treatment Outcome; D044465:White People; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D005343:Fibrinolytic Agents; D007004:Hypoglycemic Agents; D010959:Tissue Plasminogen Activator; D005905:Glyburide
keywords: acute treatment; brain swelling; cerebral edema; glyburide; hemorrhagic transformation; ischemic stroke