Glyburide Advantage in Malignant Edema and Stroke - Remedy Pharmaceuticals


Trial ID: NCT01794182


This is a randomized, multi-center, prospective, double blind study. The primary objective is to assess the efficacy and safety of glyburide (RP-1127) compared to placebo in participants with a severe anterior circulation ischemic stroke who are likely to develop malignant edema.This objective will be addressed by comparing the proportion of glyburide treated particpants and placebo treated participants with a Day 90 modified Rankin Scale (mRS) ≤ 4 without decompressive craniectomy (DC). The secondary objective is to assess the efficacy of RP-1127 compared to placebo in participants with a severe anterior circulation ischemic stroke who were likely to develop malignant edema.

Official Title

A Randomized, Multi-Center, Prospective, Double Blind, Phase II Trial of RP- 1127 (Glyburide for Injection) in Patients With a Severe Anterior Circulation Ischemic Stroke Who Are Likely to Develop Malignant Edema

Stanford Investigator(s)

Gregory W. Albers, MD
Gregory W. Albers, MD

Coyote Foundation Professor and Professor, by courtesy, of Neurosurgery


Key Inclusion Criteria:

   - A clinical diagnosis of acute ischemic stroke in the MCA territory (PCA and/or ACA
   territory involvement in addition to primary MCA territory stroke is acceptable).

   - Prior to stroke, no disability, or no significant disability despite symptoms (able to
   carry out all usual duties and activities).

   - A baseline DWI lesion between 82 and 300 cm3 on MRI.

   - Patients treated with IV rtPA should meet established criteria for IV rtPA
   administration in the 0-3 and 3-4.5 hr time periods at the time of rtPA administration
   (if rtPA is administered in the 3-4.5 hr time window, the NIHSS must be ≤ 25 at the
   time of rtPA administration).

   - The time to the start of infusion of Study Drug must be ≤ 10 hours after time of
   symptom onset, if known, or the time last seen well [termed "time last known at
   neurologic baseline" (TLK@B)].

   - Provision of written informed consent by a legally authorized representative according
   to institutional guidelines and national regulations.

Key Exclusion Criteria:

   - Commitment to decompressive craniectomy (DC) prior to enrollment, or following
   enrollment and prior to start of Study Drug.

   - Treatment with intra-arterial (IA) rtPA or by mechanical means for clot disruption.

   - Patients unable to tolerate MRI scanning, e.g. those with pacemakers or automatic

   - 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.

   - Clinical signs of herniation, e.g. one or two dilated, fixed pupils; unconsciousness
   (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.

   - Hemorrhage (other than small petechial hemorrhages) on CT/MRI, or CT/MRI evidence of
   anteroseptal/pineal shift greater ≥2 mm prior to enrollment that is due to cerebral

   - Severe renal disorder from the patient's history (e.g. dialysis) or eGFR of < 30
   mL/min/1.73 m2.

   - Severe liver disease or ALT >3 times normal, or bilirubin >2 times normal.

   - Blood glucose <55 mg/dL at enrollment or immediately prior to administration of Study
   Drug, or a clinically significant history of hypoglycemia.

   - Acute ST elevation myocardial infarction, and/or acute decompensated HF, and/or
   QTc>520 ms, and/or known history of cardiac arrest (PEA, VT, VF, asystole), and/or
   admission for an ACS, MI, or coronary intervention (PCI or coronary artery surgery)
   within the past 3 months.

   - Known sulfonylurea treatment within 7 days. Sulfonylureas include glyburide
   /glibenclamide (Diabeta, Glynase); glyburide plus metformin (Glucovance); glimepiride
   (Amaryl); repaglinide (Prandin); netaglinide (Starlix); glipizide (Glucotrol,
   GlibeneseR, MinodiabR); gliclazide (DiamicronR); tolbutamide (Orinase, Tolinase);
   glibornuride (Glutril).

   - Known allergy to sulfa or specific allergy to sulfonylurea drugs.

   - Known G6PD enzyme deficiency.

   - Pregnant women. Women must be either post-menopausal (as confirmed by the LAR),
   permanently sterilized or, if ≤ 50 years old must have a negative test for pregnancy
   obtained before enrollment.

   - Breast-feeding women who do not agree (or their LAR does not agree) to stop breast-
   feeding during Study Drug infusion and for 7 days following the end of Study Drug

   - Patients already enrolled in a non-observation-only stroke study, or with
   life-expectancy <3 months not related to current stroke, or those unlikely to be
   compliant with follow up.

   - Patients currently receiving an investigational drug.

   - Patients in whom a peripheral IV line cannot be placed.

   - Mentally incompetent (prior to qualifying stroke) patients and wards of the state.

   - Patients who, in the opinion of the investigator, are not suitable for the study
   (reason to be documented).

NOTE: Other protocol defined inclusion/exclusion criteria may apply


drug: Glyburide for Injection

drug: Placebo


Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Stephanie Kemp