Clinical Study to Evaluate the Efficacy of Febuxostat in the Treatment of Conservatively Managed Intracranial Hemorrhage Patients
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 46
- 试验地点
- 1
- 主要终点
- Change from baseline in glasgow coma scale
研究概览
简要总结
To assess the effect of Febuxostat on clinical outcomes and biomarkers of oxidative stress and inflammation in patients with conservatively managed intracranial hemorrhage.
详细描述
Intracranial hemorrhage (ICH) is a severe neurological condition characterized by bleeding within the intracranial vault, including the brain parenchyma and surrounding meningeal spaces .
It is associated with high mortality and significant morbidity, often leading to severe neurological dysfunctions . ICH can be classified into various subtypes based on the anatomical location of bleeding, including intraparenchymal hemorrhage (IPH), subarachnoid hemorrhage (SAH), subdural hematoma (SDH), epidural hematoma (EDH), and intraventricular hemorrhage (IVH) .
The pathophysiology of ICH involves both primary and secondary brain injuries. Primary brain injury results from direct mechanical damage caused by the hematoma, while secondary brain injury (SBI) is driven by oxidative stress, neuroinflammation, and disruption of the blood-brain barrier (BBB). Oxidative stress, in particular, plays a significant role in ICH progression, as the overproduction of reactive oxygen species (ROS) leads to cellular apoptosis, lipid peroxidation, and neuronal damage. Inflammatory responses further exacerbate brain injury, contributing to cognitive dysfunction and neurodegeneration .
Uric acid (UA), the end product of purine metabolism, is catalyzed by xanthine oxidase (XO) and has been implicated in cerebrovascular diseases due to its pro-oxidant properties. Hyperuricemia is associated with an increased risk of coronary heart disease, ischemic stroke, diabetes, hypertension, chronic kidney disease, and gout. Moreover, elevated UA levels may worsen ICH prognosis, leading to higher mortality and more severe symptoms.
Xanthine oxidase plays a crucial role in ROS production during the conversion of hypoxanthine to xanthine and UA, generating hydrogen peroxide (H₂O₂) and superoxide anion (O₂-), both of which contribute to oxidative stress and vascular damage. These oxidative molecules increase microvascular permeability and can further propagate secondary brain injury in ICH .
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 (Participant)
盲法说明
This is a single-blind study where the participants (patients) are blinded to the treatment assigned. Medications and standard care are administered while ensuring that the participant remains unaware of whether they are receiving Febuxostat or standard therapy alone
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •• Age ≥ 18 years old.
- •Diagnosed with intracranial hemorrhage confirmed by CT scan.
- •Managed conservatively regarding clinical guidelines.
- •Able to provide informed consent or have a legal representative provide consent.
排除标准
- •• Patients with a history of previous brain surgery or significant neurological disorders.
- •Severe comorbidities (e.g., uncontrolled diabetes, severe cardiac disease).
- •Allergy or contraindication to febuxostat.
- •Pregnant or breastfeeding women.
- •Patients requiring surgical intervention for hematoma evacuation.
- •Renal impairment with SCr > 4
- •Liver impairment with INR > 5
- •Significant deterioration ( GCS < 8 )
研究组 & 干预措施
Interventional group
Patients will receive Febuxostat 40 mg once daily in addition to the standard traditional therapy of conservatively managed intracranial hemorrhage for three
干预措施: Febuxostat 40 mg (Drug)
结局指标
主要结局
Change from baseline in glasgow coma scale
时间窗: Baseline,1week,1monthand 3 months
The GCS is used to assess the patient's level of consciousness based on eye, verbal, and motor responses, with a total score ranging from 3 (severe impairment) to 15 (normal). Higher scores indicate better clinical outcomes
次要结局
- Change from baseline in inflammatory and neuroinjury biomarkers(Baseline and 3 months)
- Radiological assessment via non-contrast computed tomography (NCCT)(Baseline and 3 months)
- Change from baseline in C-reactive protein (CRP) level at 3 months(Baseline and 3 months)
- Change from baseline in Erythrocyte sedimentation rate (ESR) at 3 months.(Baseline and 3 months)
- Change from baseline in Serum Interleukin-1 beta (IL-1β) at 3 months.(Baseline and 3 months)
- Change from baseline in Serum S100B protein at 3 months.(Baseline and 3 months)
研究者
Merihan Elhadidi Elhadidi
Clinical pharmacist
Tanta University