A Randomized Clinical Trial of Glyburide (RP-1127) for TBI
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 29
- 试验地点
- 4
- 主要终点
- Change from Baseline in Hemorrhage
研究概览
简要总结
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.
详细描述
This study was previously posted by Remedy Pharmaceuticals, Inc. and has since been acquired by Biogen.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Documented closed head TBI
- •Clearly defined time of injury no more than 10 hours before administration of study drug/placebo
- •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.
- •Age 18-75 years
- •Patients in whom a dedicated peripheral IV line can be placed for study drug administration
- •Written consent obtained from legally authorized representative (LAR)
排除标准
- •No documented TBI or time of impact not certain
- •Penetrating brain injury
- •Spinal column instability and/or spinal cord injury with neurodeficit
- •Concomitant severe non survivable injury
- •Pregnant, or a positive pregnancy test
- •Women who intend to breastfeed during Study Days 1-
- •Blood glucose <50mg/dL
- •Severe renal disorder from the patient's history (e.g. dialysis) or serum creatinine of > 2.5 mg/dL
- •Severe liver disease or total bilirubin >1.5 times upper limit of normal
- •Systolic BP<90 mm Hg not responsive to fluid resuscitation
- •Blood alcohol > 250mg/dL
- •Inability to have MRI (pacemaker, non-MR compatible pressure monitor, etc.)
- •Hospitalization for brain injury, psychiatric or neurological disease within previous 3 years
- •Emergent or urgent surgical operation anticipated (in OR, bedside procedures excluded) that would prevent dosing with study drug within 8 hours of injury.
- •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.)
- •Use of sulfonylurea drugs within the prior 30 days
- •Treatment with another investigational drug within the prior 30 days
- •Allergy to sulfonylurea drugs
- •Known diagnosis of G6PD enzyme deficiency
- •PaO2 < 60 mm Hg on admission (for patients in whom blood gases are drawn per standard of care)
- •Non-English speaking legally authorized representative and subjects (University of Maryland only)
- •Prisoners or others who may be unable to make a truly voluntary and uncoerced decision whether or not to participate in the study
- •Any other clinical condition which in the opinion of the investigator makes the patient unsuitable for inclusion into the study
研究组 & 干预措施
Glyburide
Glyburide delivered by injection as an approximately 2 minute loading dose followed by 72 hours of continuous infusion.
干预措施: Glyburide (Drug)
Placebo
Matching placebo delivered by injection as an approximately 2 minute loading dose followed by 72 hours of continuous infusion.
干预措施: Placebo (Drug)
结局指标
主要结局
Change from Baseline in Hemorrhage
时间窗: Baseline, Day 3, Day 90, and Day 180
To be assessed using MRI.
Change from Baseline in Edema
时间窗: Baseline, Day 3, Day 90, and Day 180
To be assessed using Magnetic Resonance Imaging (MRI).
Number of Participants with Adverse Events and Serious Adverse Events
时间窗: Up to 180 Days
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
次要结局
- Change from Baseline in Glasgow Coma Scale (GCS)(Baseline up to Day 7)
- Number of Participants with Abnormalities Associated with Brain Swelling(Baseline, Day 3, Day 90, and Day 180)
- Number of All-Cause and Neurological Mortalities(Up to Day 180)
- Change from Baseline in Intracranial Pressure (ICP)(Baseline up to Day 7)
- Change from Baseline in Brain Volume(Baseline, Day 3, Day 90, and Day 180)
- Change from Day 30 in Extended Glasgow Outcome Scale (GOS-E)(Day 30, Day 60, Day 90, and Day 180)
- Number of Participants Requiring Decompression Craniectomy(Baseline up to Day 7)
- Number of Participants Experiencing Neuroworsening(Baseline up to Day 7)
- PK Parameter: Steady State Concentration of Glyburide(Baseline and 36 hours)