Pilot study of intravenous glyburide in patients with a large ischemic stroke.

Abstract

BACKGROUND AND PURPOSE:

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.

CLINICAL TRIAL REGISTRATION:

URL: http://www.clinicaltrials.gov. Unique identifier: NCT01268683.

• Authors: Kevin N Sheth, W Taylor Kimberly, Jordan J Elm, Thomas A Kent, Pitchaiah Mandava, Albert J Yoo, Götz Thomalla, Bruce Campbell, Geoffrey A Donnan, Stephen M Davis, Gregory W Albers, Sven Jacobson, J Marc Simard, Barney J Stern
• Journal: Stroke (Stroke) Vol. 45 Issue 1 Pg. 281-3 (Jan 2014) ISSN: 1524-4628 [Electronic] United States
• PMID: 24193798 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

• Blood Glucose
• Fibrinolytic Agents
• Hypoglycemic Agents
• Tissue Plasminogen Activator
• Glyburide

Topics

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Blood Glucose (metabolism)
• Brain Edema (drug therapy, etiology)
• Brain Ischemia (drug therapy)
• Comorbidity
• Female
• Fibrinolytic Agents (therapeutic use)
• Glyburide (administration & dosage, adverse effects, therapeutic use)
• Humans
• Hypoglycemia (chemically induced)
• Hypoglycemic Agents (administration & dosage, adverse effects, therapeutic use)
• Injections, Intravenous
• Magnetic Resonance Imaging
• Male
• Middle Aged
• Patient Safety
• Pilot Projects
• Prospective Studies
• Stroke (drug therapy)
• Tissue Plasminogen Activator (therapeutic use)
• Treatment Outcome
• White People
• Young Adult