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Glyburide (RP-1127) for Traumatic Brain Injury (TBI)

This study is currently recruiting participants.
Verified January 2013 by Remedy Pharmaceuticals, Inc.
Sponsor:
Collaborators:
U.S. Army Medical Research and Materiel Command
INTRuST, Post-Traumatic Stress Disorder - Traumatic Brain Injury Clinical Consortium
Information provided by (Responsible Party):
Remedy Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT01454154
First received: October 11, 2011
Last updated: January 21, 2013
Last verified: January 2013
History of Changes
  Purpose

This is a randomized, double-blind, placebo-controlled, multi-institutional study of IV RP-1127 (Glyburide for Injection) begun within 10 hours of complicated mild, moderate or severe traumatic brain injury (TBI).


Condition Intervention Phase
Traumatic Brain Injury
 Drug: Glyburide
Drug: Placebo
 Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized Clinical Trial of Glyburide (RP-1127) for TBI

Resource links provided by NLM:

Drug Information available for: Glyburide
U.S. FDA Resources

Further study details as provided by Remedy Pharmaceuticals, Inc.:

Primary Outcome Measures:
  • Change in Edema from Baseline [ Time Frame: 72 hr ] [ Designated as safety issue: No ]
    Edema [ADC (apparent diffusion coefficient) (mm2/sec); Volume (mm3); FW (free water) (normalized units); ADC_t (apparent diffusion coefficient, tissue) (mm2/sec)] will be assessed by imaging.

  • Change in Hemorrhage from Baseline [ Time Frame: 72 hr ] [ Designated as safety issue: No ]
    Hemorrhage [Hemorrhagic Burden Index (no units); Number of hemorrhagic lesions; Size of hemorrhagic lesions] will be assessed by imaging.

  • Safety i.e. the incidence of mortality, adverse events, and serious adverse events [ Time Frame: Through 180 Days ] [ Designated as safety issue: Yes ]
    Safety will be assessed by a review of the incidence of mortality, adverse events, and serious adverse events, as well as by analysis of relevant laboratory data, blood glucose, and ECG's.


Estimated Enrollment: 100
Study Start Date: November 2011
Estimated Study Completion Date: September 2014
Estimated Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Glyburide
RP-1127 (Glyburide for Injection)
 Drug: Glyburide
RP-1127 (Glyburide for Injection) delivered as an approximately 2 minute loading dose followed by 72 hours of continuous infusion.
Other Names:
  • glyburide
  • glibenclamide
Placebo Comparator: Placebo
Placebo
 Drug: Placebo
Placebo delivered as an approximately 2 minute loading dose followed by 72 hours of continuous infusion.

Detailed Description:

The primary efficacy objective of this study is to assess whether patients with severe, moderate, or complicated mild TBI administered RP-1127 will show a decrease in MRI-defined edema and/or hemorrhage, compared to patients administered placebo.

The primary safety objective is to assess the safety and tolerability of RP-1127 compared to placebo in patients with severe, moderate, or complicated mild TBI.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Documented closed head TBI
  2. Clearly defined time of injury no more than 10 hours before administration of study drug/placebo
  3. GCS 4-14. The GCS will be obtained free of the effects of sedating and/or paralytic drug. Complicated mild must have GCS 13-14 and one or more of the following: Intraparenchymal clots or contusions in aggregate > 10cc; Midline shift > 5mm; IVH, SDH, EDH seen on more than one CT scan slice.
  4. Age 18-75 years
  5. Patients in whom a dedicated peripheral IV line can be placed for study drug administration
  6. Written consent obtained from legally authorized representative (LAR)

Exclusion Criteria:

  1. No documented TBI or time of impact not certain
  2. Penetrating brain injury
  3. Spinal column instability and/or spinal cord injury with neurodeficit
  4. Concomitant severe non survivable injury
  5. Pregnant, or a positive pregnancy test
  6. Women who intend to breastfeed during Study Days 1-4.
  7. Blood glucose <50mg/dL
  8. Severe renal disorder from the patient's history (e.g. dialysis) or serum creatinine of > 2.5 mg/dL
  9. Severe liver disease or total bilirubin >1.5 times upper limit of normal
  10. INR>1.4
  11. Systolic BP<90 mm Hg not responsive to fluid resuscitation
  12. Blood alcohol > 250mg/dL
  13. Inability to have MRI (pacemaker, non-MR compatible pressure monitor, etc.)
  14. Hospitalization for brain injury, psychiatric or neurological disease within previous 3 years
  15. Emergent or urgent surgical operation anticipated (in OR, bedside procedures excluded) that would prevent dosing with study drug within 8 hours of injury.
  16. Known use of Coumadin (warfarin), Plavix (clopidogrel), Effient (prasugrel) or Pletal (cilostazol), heparin, low molecular weight heparin, heparinoids, or abciximab or similar antiplatelet agents in the previous 72 hours (Note that patients later found to have taken these medications will not be automatically excluded from the study.)
  17. Use of sulfonylurea drugs within the prior 30 days
  18. Treatment with another investigational drug within the prior 30 days
  19. Allergy to sulfonylurea drugs
  20. Known diagnosis of G6PD enzyme deficiency
  21. PaO2 < 60 mm Hg on admission (for patients in whom blood gases are drawn per standard of care)
  22. Non-English speaking legally authorized representative and subjects (University of Maryland only)
  23. Prisoners or others who may be unable to make a truly voluntary and uncoerced decision whether or not to participate in the study
  24. Any other clinical condition which in the opinion of the investigator makes the patient unsuitable for inclusion into the study
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01454154

Contacts
Contact: Howard Eisenberg, MD (410) 328-3514 heisenberg@smail.umaryland.edu

Locations
United States, California
University of California, San Diego Recruiting
San Diego, California, United States, 92103
Contact: Vishal Bansal, MD     619-543-7096     v3bansal@ucsd.edu    
United States, Maryland
University of Maryland Medical Center, Shock Trauma Center Recruiting
Baltimore, Maryland, United States, 21201
Contact: Howard Eisenberg, MD     410-328-3514     heisenberg@smail.umaryland.edu    
Sponsors and Collaborators
Remedy Pharmaceuticals, Inc.
U.S. Army Medical Research and Materiel Command
INTRuST, Post-Traumatic Stress Disorder - Traumatic Brain Injury Clinical Consortium
Investigators
Principal Investigator: Howard Eisenberg, MD University of Maryland
  More Information

No publications provided

Responsible Party: Remedy Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT01454154     History of Changes
Other Study ID Numbers: RPI 202, INTRuST-GLY
Study First Received: October 11, 2011
Last Updated: January 21, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Remedy Pharmaceuticals, Inc.:
TBI
Traumatic Brain Injury

Additional relevant MeSH terms:
Brain Injuries
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Craniocerebral Trauma
Trauma, Nervous System
 Wounds and Injuries
Glyburide
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on May 23, 2013