A Randomized Control Trial of Baricitinib Administration in Patients With Moderate and Severe Traumatic Intracerebral Hemorrhage/Contusions
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 100
- 试验地点
- 1
- 主要终点
- Clinical improvement
研究概览
简要总结
The purpose of the present study is to study the effect of baricitinib administration on outcome of participants with moderate and severe traumatic intracerebral hemorrhage/contusions. A multi-center randomized control trial will be conducted. Participants with a radiological diagnosis of traumatic intracerebral hemorrhage/contusions and an initial GCS score of 5-12 will be screened and enrolled in the first 24 hours after traumatic brain injury.
详细描述
Traumatic brain injury (TBI) remains one of the biggest public health problems and represents a major cause of death or severe disability in young people and adults. Previous studies have confirmed that an infammatory response occurs directly after TBI, which contribute to the development of cerebral edema and swelling, a breakdown of the blood-brain barrier, and delayed neuronal cell death, thus application of agents with anti-infammatory actions may be promising to improve the functional outcomes for TBI patients. Activated Janus kinases (JAKs) play pivotal roles in intracellular signaling from cell-surface receptors for multiple cytokines implicated in the pathologic processes of TBI, selective JAK1 and JAK2 inhibitors (AG490 and abroctinib) have been shown to reduce the brain edema and improve neurological function for TBI rodents. Baricitinib, an orally available small molecule, provides reversible inhibition of JAK1 and JAK2 and has shown clinical efficacy in studies involving patients with rheumatoid arthritis, COVID-19 and alopecia areata, and was very safe for patients. Therefore, in the current study, a multicenter randomized control trial will be conducted to study the therapeutic efficacy of baricitinib for patients with moderate and severe traumatic intracerebral hemorrhage/contusions, comparing with the standard treatment only.The patients with the GCS scores of 5-12 will be enrolled according to the inclusive and exclusive criteria. The primary outcome is the Glasgow Outcome Scale at 180 days after brain trauma. And the secondary outcome including In-hospital mortality rate, and mortality rate at 90 days, 180 days after brain trauma; Glasgow Coma Scale at discharge; The Glasgow Outcome Scale at 90 days after brain trauma; The levels of serum inflammatory factors TNF-α、IFN-γ、IL-1β、IL-6、IL-8 at 2 to 7 days after brain trauma; Volume of edema around intracerebral hemorrhage/contusions at 2 to 7 days after brain trauma;The mean value of intracranial pressure at 2 to 7 days after brain trauma and The incidence of in-hospital pneumonia.
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
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 18 years older and younger than 80 years old.
- •Definite history of traumatic brain injury.
- •Admission within≤24 hours after the traumatic brain injury.
- •CT scans demonstrate intracerebral hemorrhage/contusions with and without extracerebral hemorrhage (epi- and sub- dural hemorrhage)
- •GCS score of 5 or greater and no more than 12 at time of enrollment.
- •Closed head injury.
- •Admission without infections
- •Signed and dated informed consent by the subject, legally authorized representative, or surrogate obtained.
排除标准
- •Time of head injury cannot be reliably assessed.
- •Subjects is considered a candidate for immediate surgical intervention because of severe extracranial injury.
- •Open head injury.
- •Pregnancy or parturition within previous 30 days or active lactation.
- •Use of Janus kinase inhibitors (baricinitib,abroctinib, AG490 and etc.)
- •Pre-traumatic dementia or disability.
- •With severe liver, kidney disease, or malignancy, life expectancy is less than 14 days.
- •Severe pulmonary infection.
- •Severe or acute heart failure.
- •Severe infections within previous 30 days.
- •History of myocardial infarction.
- •Known sensitivity to baricinitib.
- •Severe decreases in neutrophil, lymphocyte and platelet counts, severe decrease in hemoglobin.
- •Severe liver and kidney dysfunction.
- •Currently participating in other interventional clinical trials.
研究组 & 干预措施
Baricitinib group
Besides receiving standard treatment and care, baricitinib will be administrated orally (or crushed for nasogastric tube delivery) and given daily at the dosage of 4mg, for consecutive 14 days after patients' brain injury.
干预措施: Baricitinib 4 MG (Drug)
Control group
Participants will receive standard treatment and care according to the current management guidelines for traumatic brain injury, e.g. the guideline made by U.S. Brain Trauma Foundation (BTF)
干预措施: Standard treatment (Other)
结局指标
主要结局
Clinical improvement
时间窗: up to 180 days
Glasgow Outcome Scale at 180 days after brain trauma
次要结局
- Mortality rate(up to 180 days)
- Coma severity(up to 2 weeks)
- Glasgow Outcome Scale(up to 90 days)
- Serum inflammatory factors(up to 7 days)
- Volume of edema around intracerebral hemorrhage/contusions(up to 7 days)
- Intracranial pressure(up to 7 days)
- The incidence of pneumonia(up to 2 weeks)