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Glyburide Advantage in Malignant Edema and Stroke - Remedy Pharmaceuticals (GAMES-RP)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01794182
Recruitment Status : Unknown
Verified May 2015 by Remedy Pharmaceuticals, Inc..
Recruitment status was:  Active, not recruiting
First Posted : February 18, 2013
Last Update Posted : June 2, 2015
Information provided by (Responsible Party):
Remedy Pharmaceuticals, Inc.

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

Condition or disease Intervention/treatment Phase
Ischemic Stroke Malignant Edema Drug: RP-1127 (Glyburide for Injection) Phase 2

Detailed Description:

The study population consists of subjects with a clinical diagnosis of acute severe anterior circulation ischemic stroke, a baseline diffusion weighted image (DWI) lesion between 82 and 300 cm3, age 18-80 years, and time from symptom onset to start of study infusion of ≤10 hours. The study will enroll both patients that do not receive IV rtPA and those that receive IV rtPA within 4.5 hours of stroke.

Enrollment will be randomized controlling for site, age ≤60 (yes/no), and IV rtPA treatment at baseline (yes/no). Subjects will be randomized equally between RP-1127 and placebo.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 83 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
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
Study Start Date : May 2013
Estimated Primary Completion Date : August 2015
Estimated Study Completion Date : April 2016

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Anthrax Edema
Drug Information available for: Glyburide

Arm Intervention/treatment
Placebo Comparator: Matching Placebo
Subjects will receive matching placebo.
Experimental: RP-1127 (Glyburide for Injection)
Subjects will receive the active agent, RP-1127 (Glyburide for Injection)
Drug: RP-1127 (Glyburide for Injection)
Glyburide (5-chloro-N-(4-[N-(cyclohexylcarbamoyl) sulfamoyl]phenethyl)-2- methoxybenzamide) is an anti-diabetic medication in a class of medications known as sulfonylureas. RP-1127 is a formulation of glyburide designed for intravenous administration.
Other Names:
  • glibenclamide
  • glybenclamide

Primary Outcome Measures :
  1. The proportion of patients with a modified Rankin Scale (mRS) at Day 90 ≤ 4 without decompressive craniectomy [ Time Frame: 90 Days ]
  2. Safety of RP-1127 in subjects with a severe anterior circulation ischemic stroke who are likely to develop malignant edema. [ Time Frame: 90 Days ]
    Addressed by comparing the frequency and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs)in the RP-1127 and placebo groups, with a specific focus on all cause mortality, cardiac mortality, and cardiac-related and blood glucose-related AEs/SAEs.

Secondary Outcome Measures :
  1. Proportion of subjects undergoing DC or dead within 14 days [ Time Frame: 14 days ]
  2. The change between baseline and 72-96 hours in ipsilateral hemispheric swelling measured by MRI [ Time Frame: 96 hours ]
  3. The change between baseline and 72-96 hours in lesional swelling measured by MRI [ Time Frame: 96 hours ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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)].
  • Age ≥18 years and ≤80 years.
  • Provision of written informed consent by a legally authorized representative according to institutional guidelines and national regulations.

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 defibrillators.
  • 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 edema.
  • 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 infusion.
  • 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).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01794182

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Sponsors and Collaborators
Remedy Pharmaceuticals, Inc.
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Principal Investigator: Kevin N Sheth, MD Yale University
Principal Investigator: W. Taylor Kimberly, MD, PhD Massachusetts General Hospital
Publications automatically indexed to this study by Identifier (NCT Number):

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Responsible Party: Remedy Pharmaceuticals, Inc. Identifier: NCT01794182    
Other Study ID Numbers: RPI 203
First Posted: February 18, 2013    Key Record Dates
Last Update Posted: June 2, 2015
Last Verified: May 2015
Additional relevant MeSH terms:
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Gas Gangrene
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Bacillaceae Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Clostridium Infections
Hypoglycemic Agents
Physiological Effects of Drugs