Multi-Arm Multi-Stage Adaptive Platform Trial (APT) for the Acute Treatment of Traumatic Brain Injury
试验速览
- 阶段
- 2 期
- 状态
- Enrolling By Invitation
- 入组人数
- 672
- 试验地点
- 18
- 主要终点
- Change in Glasgow Outcome Scale-Extended (GOSE 2-Way)
研究概览
简要总结
The purpose of this study is to determine if experimental drug treatment improves recovery after TBI as compared to a control (placebo) group. Changes in recovery will be measured throughout the study. The study drugs listed below are approved by the U.S. Food and Drug Administration (FDA) but are being used "off-label" in this study. This means that the drugs are not currently approved to treat TBI.
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 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adults (18-65 years of age, inclusive)
- •Presents to a participating enrollment site and is able to receive first dose within 24 hours of non-penetrating head injury warranting clinical evaluation with a non-contrast head CT based on American College of Emergency Physicians (ACEP) Centers for Disease Control and Prevention (CDC) clinical policy for TBI imaging.
- •Closest, prior to Randomization Glasgow Coma Scale (GCS) score of 9 to 15
- •Acute trauma-related neuroimaging abnormality (subarachnoid hemorrhage, contusion, subdural hematoma, petechial hemorrhage, intraventricular hemorrhage) on cranial CT (CT+)
- •Initial Glial Fibrillary Acidic Protein (GFAP) blood level >100 pg/ml ≤ 15,000 pg/ml determined using a for Research Use Only (RUO) assay(s) or an Investigation Use Only (IUO) assay(s)
- •Persons of childbearing potential (i.e., those not postmenopausal or surgically sterile) may participate provided that they are using adequate birth control methods for the duration of investigational product administration (see manual of procedures for adequate birth control methods)
- •Participants able to undergo Magnetic Resonance Imaging (MRI) scans, no contraindications
- •Participants or legally authorized representative (LAR) willing and able to provide informed consent
- •Participants or LAR able to read, speak, and understand English or Spanish (participating site dependent, where available), including the informed consent form (ICF)
- •Willingness and ability to comply with all study procedures, treatment, and follow-up
排除标准
- •Isolated epidural hematoma
- •Pre-existing conditions including disabling developmental, neurologic, psychiatric, medical disorder that continues to produce functional disability up to the time of injury; or imminent death based on clinical judgement
- •Current enrollment in another interventional study
- •Currently pregnant or currently breastfeeding or planning on becoming pregnant in the next 6 months
- •Current incarceration or in custody
- •Currently prescribed one of the investigational products (or other drugs in the same class) prior to injury; or contra-indicated or as listed in the appendices
- •Hypersensitivity or intolerance to investigational products or the investigational products' respective classes
- •Renal dysfunction (Creatinine Clearance (CrCl) or estimated Glomerular Filtration Rate (eGFR) (<60 mL/minute/1.73 m2)
- •Acute liver disease or hepatic dysfunction (ALT/AST >3 times upper limit of normal lab value)
- •Hemodynamic instability, per participating site physician investigator clinical judgment
- •Inability to swallow investigational product capsule
- •Unable or unwilling to consume animal byproducts, has a gelatin allergy, and/or religious beliefs that do not permit consuming gelatin
- •Intolerance to small amounts of lactose (less than ½ teaspoonful) daily
- •Low likelihood of follow up or study compliance, or any other reason, in the opinion of the participating site investigator, the participants should not participate in the study
研究组 & 干预措施
Intervention 1: Atorvastatin calcium (ATOR)
By Mouth (PO) Twice a day (BID) 80 mg/day, with no loading dose, for 28 days
干预措施: Atorvastatin Calcium (Drug)
Intervention 2: Minocycline hydrochloride (MINO)
By Mouth (PO) Twice a day (BID) 200 mg loading dose on Day 1, then 100 mg twice daily for 6 days, then placebo twice daily for 21 days
干预措施: Minocycline Hydrochloride (Drug)
Intervention 3: Candesartan cilexetil (CAND)
By Mouth (PO) Twice a day (BID) 8 mg once on Day 1, then 16 mg daily for 27 days
干预措施: Candesartan Cilexetil (Drug)
Matching Placebo
By Mouth (PO) Twice a day (BID) 2 capsules 2x/day
干预措施: Placebo (Drug)
结局指标
主要结局
Change in Glasgow Outcome Scale-Extended (GOSE 2-Way)
时间窗: 2 weeks to 3 months postinjury
Functional impairment due only to the TBI will be measured using the GOSE Scale-Extended (GOSE 2-Ways). The score ranges from 1-8, with higher scores indicating better recovery. Change will be measured from Week 2 to Month 3 postinjury and compared to placebo.
次要结局
- Imaging biomarkers(2 weeks to 3 months postinjury)
- Post-TBI cognitive outcome (BTACT)(Day 3 to Week 4 postinjury)
- Post-TBI symptom outcome (Rivermead)(Day 3 to Week 4)
- Change in Blood-based biomarkers (Neurofilament light chain)(Week 2)
- Blood-based biomarker (GFAP)(Week 2)