Clinical trial NCT01454154: Glyburide (RP-1127) for Traumatic Brain Injury (TBI)
Official title: A Randomized Clinical Trial of Glyburide (RP-1127) for TBI
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Traumatic Brain Injury
Lead sponsor: Remedy Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
Collaborators: name: U.S. Army Medical Research and Development Command
name: INTRuST, Post-Traumatic Stress Disorder - Traumatic Brain Injury Clinical Consortium
First posted: 2011-10-18
Enrollment: 29
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Change from Baseline in Edema
timeFrame: Baseline, Day 3, Day 90, and Day 180
measure: Change from Baseline in Hemorrhage
timeFrame: Baseline, Day 3, Day 90, and Day 180
measure: Number of Participants with Adverse Events and Serious Adverse Events
timeFrame: Up to 180 Days
Secondary outcomes:
measure: Change from Baseline in Brain Volume
timeFrame: Baseline, Day 3, Day 90, and Day 180
measure: Number of Participants with Abnormalities Associated with Brain Swelling
timeFrame: Baseline, Day 3, Day 90, and Day 180
measure: Change from Baseline in Glasgow Coma Scale (GCS)
timeFrame: Baseline up to Day 7
measure: Change from Baseline in Intracranial Pressure (ICP)
timeFrame: Baseline up to Day 7
measure: Change from Day 30 in Extended Glasgow Outcome Scale (GOS-E)
timeFrame: Day 30, Day 60, Day 90, and Day 180
measure: Number of Participants Requiring Decompression Craniectomy
timeFrame: Baseline up to Day 7
measure: Number of Participants Experiencing Neuroworsening
timeFrame: Baseline up to Day 7
measure: PK Parameter: Steady State Concentration of Glyburide
timeFrame: Baseline and 36 hours
measure: Number of All-Cause and Neurological Mortalities
timeFrame: Up to Day 180
Other outcomes:
Locations:
city: San Diego
country: United States
facility: University of California, San Diego
state: California
city: Baltimore
country: United States
facility: University of Maryland Medical Center, Shock Trauma Center
state: Maryland
city: Pittsburgh
country: United States
facility: UPMC Presbyterian Hospital
state: Pennsylvania
city: Richmond
country: United States
facility: VCU Medical Center
state: Virginia
Study officials:
affiliation: Remedy Pharmaceuticals
name: Medical Director
role: STUDY_DIRECTOR
References: