Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization effort.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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.
 
ClinicalTrials.gov Identifier: NCT01794182
Recruitment Status : Completed
First Posted : February 18, 2013
Last Update Posted : June 22, 2021
Sponsor:
Information provided by (Responsible Party):
Biogen

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Ischemic Stroke Malignant Edema Drug: Glyburide for Injection Drug: Placebo Phase 2

Detailed Description:

The study population consists of participants 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 participants that do not receive intravenous (IV) recombinant tissue plasminogen activator (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). Participants will be randomized equally between glyburide and placebo.

This study was previously posted by Remedy Pharmaceuticals, Inc. and has since been acquired by Biogen.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 86 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
Actual Study Start Date : June 13, 2013
Actual Primary Completion Date : April 4, 2016
Actual Study Completion Date : April 4, 2016

Resource links provided by the National Library of Medicine

Drug Information available for: Glyburide

Arm Intervention/treatment
Placebo Comparator: Matching Placebo
Participants received a bolus dose of matching placebo over 2 minutes, followed by a continuous matching placebo infusion for 72 hours.
Drug: Placebo
Administered as specified in the treatment arm.

Experimental: Glyburide for Injection
Participants received a 0.13 mg bolus dose of glyburide over 2 minutes, followed by a 0.16 mg/hr continuous infusion for 6 hours and than a 0.11 mg/hr for 66 hours for a total dosing period of 72 hours.
Drug: Glyburide for Injection
Administered as specified in the treatment arm.
Other Names:
  • RP-1127
  • glibenclamide
  • glybenclamide




Primary Outcome Measures :
  1. Percentage of Participants with a Modified Rankin Scale (mRS) score of ≤ 4 Without Decompressive Craniectomy (DC) [ Time Frame: Day 90 ]
    The mRS scale runs from 0-6, the scoring is as follows: 0 - No symptoms, 1 - No significant disability, 2 - Slight disability, 3 - Moderate disability, 4 - Moderately severe disability, 5 - Severe disability, 6 - Dead

  2. Number of Participants with Adverse Events and Serious Adverse Events [ Time Frame: Up to 1 Year ]
    An adverse event (AE) is any symptom, sign, illness or experience that develops or worsens in severity during the course of the study. A serious adverse event is any AE that is fatal, life-threatening, requires or prolongs hospital stay, results in persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event


Secondary Outcome Measures :
  1. Percentage of Participants Undergoing DC or Dead [ Time Frame: Baseline and Day 14 ]
  2. Change from Baseline in Ipsilateral Hemispheric Swelling [ Time Frame: Baseline up to 72-96 Hours ]
    To be assessed using Magnetic Resonance Imaging (MRI).

  3. Change from Baseline in Lesional Swelling [ Time Frame: Baseline up to 72-96 Hours ]
    To be assessed using MRI.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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

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 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).

NOTE: Other protocol defined inclusion/exclusion criteria may apply


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 ClinicalTrials.gov identifier (NCT number): NCT01794182


Locations
Show Show 17 study locations
Sponsors and Collaborators
Biogen
Investigators
Layout table for investigator information
Study Director: Medical Director Biogen
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Layout table for additonal information
Responsible Party: Biogen
ClinicalTrials.gov Identifier: NCT01794182    
Other Study ID Numbers: 252LH203
RPI 203 ( Other Identifier: Remedy Pharmaceuticals, Inc. )
First Posted: February 18, 2013    Key Record Dates
Last Update Posted: June 22, 2021
Last Verified: June 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Anthrax
Gas Gangrene
Stroke
Ischemic Stroke
Edema
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Bacillaceae Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Bacterial Infections and Mycoses
Infections
Clostridium Infections
Glyburide
Hypoglycemic Agents
Physiological Effects of Drugs