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

NCT ID: NCT01454154

Last Updated: 2024-11-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 29 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-12-17
• Study Completion Date: 2015-02-20

Brief Summary

The primary objectives of this study are to assess whether participants with traumatic brain injury (TBI) administered glyburide begun within 10 hours of injury will show a decrease in magnetic resonance imaging (MRI)-defined edema and/or hemorrhage, compared to placebo and to assess the safety and tolerability of glyburide compared to placebo in participants with TBI. The secondary objectives include analyzing brain cell loss, computerized tomography (CT) scan /MRI abnormalities, reduction of mortality and or improvement of function or physiology, incidence of decompression craniectomy, incidence of neuroworsening, and to assess the steady state concentrations of glyburide in TBI participants.

Conditions

Traumatic Brain Injury

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Glyburide

Glyburide delivered by injection as an approximately 2 minute loading dose followed by 72 hours of continuous infusion.

Group Type: EXPERIMENTAL

Glyburide

Intervention Type: DRUG

Administered as specified in the Treatment Arm.

Placebo

Matching placebo delivered by injection as an approximately 2 minute loading dose followed by 72 hours of continuous infusion.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Administered as specified in the Treatment Arm.

Interventions

Glyburide

Administered as specified in the Treatment Arm.

Intervention Type: DRUG

Placebo

Administered as specified in the Treatment Arm.

Intervention Type: DRUG

Other Intervention Names

RP-1127; glibenclamide; glybenclamide

Eligibility 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

U.S. Army Medical Research and Development Command

FED

Sponsor Role: collaborator

INTRuST, Post-Traumatic Stress Disorder - Traumatic Brain Injury Clinical Consortium

OTHER

Sponsor Role: collaborator

Remedy Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Remedy Pharmaceuticals

Locations

University of California, San Diego

San Diego, California, United States

University of Maryland Medical Center, Shock Trauma Center

Baltimore, Maryland, United States

UPMC Presbyterian Hospital

Pittsburgh, Pennsylvania, United States

VCU Medical Center

Richmond, Virginia, United States

Countries

United States

Other Identifiers

INTRuST-GLY

Identifier Type: OTHER

Identifier Source: secondary_id

RPI 202

Identifier Type: -

Identifier Source: org_study_id