Intracranial Hemorrhage
Conditions
Keywords
Intracranial hemorrhage
Brief summary
To assess the effect of Febuxostat on clinical outcomes and biomarkers of oxidative stress and inflammation in patients with conservatively managed intracranial hemorrhage.
Detailed description
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 . A powerful non-purine selective xanthine oxidase inhibitor (XOI), Febuxostat was approved by the FDA in 2009 for the treatment hyperuricemia in gout patients. According to recent research, Feb has neuroprotective effects on cerebral ischemia-reperfusion in rats and is beneficial against cardiac ischemia-reperfusion injury. In animal studies, Feb helped neurocognitive performance in mice following a brain hemorrhage. Feb was more likely to be involved in neuroprotection following cerebral hemorrhage by influencing inflammation-related pathways, based on analysis of genes after hemorrhage. Feb could attenuate the activation of the NLRP3 inflammasome, a crucial inflammatory molecule in neuroinflammation, and lower the level of inflammatory factors following cerebral hemorrhage. Feb also lowered neuronal degeneration and neuronal death in brain tissues. The protective benefits of Feb were discovered following secondary injury in cerebral hemorrhage using bioinformatics and pharmacological approaches. While preclinical research in animal models is promising, transferring these findings into clinical applications is essential to assess the neuroprotective effect of Feb in patients with intracranial hemorrhage, human model.
Interventions
DRUGFebuxostat 40 mg
Participants in this arm will receive Febuxostat at a dose of 40 mg orally once daily for a duration of three months, administered in addition to the standard traditional therapy for conservatively managed intracranial hemorrhage
DRUGStandard medical treatment
Participants in this arm will receive only the standard traditional medical guidelines and therapy for conservatively managed intracranial hemorrhage for a duration of three months
Sponsors
Tanta University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Masking description
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
Intervention model description
A randomized, controlled, parallel-group, single-blind clinical trial. Eligible participants are assigned in a 1:1 ratio to either the active interventional group (receiving Febuxostat 40 mg once daily plus standard traditional therapy) or the positive control group (receiving standard traditional therapy only) for a total duration of 3 months
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* • 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.
Exclusion criteria
* • 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 )
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline in glasgow coma scale | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Radiological assessment via non-contrast computed tomography (NCCT) | Baseline and 3 months | NCCT imaging will be used to evaluate hematoma stability, resolution, expansion, or complications (such as perihematomal edema, mass effect, or midline shift) in intracranial hemorrhage patients. |
| Change from baseline in C-reactive protein (CRP) level at 3 months | Baseline and 3 months | Blood samples will be analyzed to measure the change in levels of specific inflammatory biomarkers to evaluate the effect of Febuxostat on neuroinflammation and oxidative stress. The biomarkers include: C-reactive protein (CRP) level ( mg/l) |
| Change from baseline in Erythrocyte sedimentation rate (ESR) at 3 months. | Baseline and 3 months | Blood samples will be analyzed to measure the change in levels of specific inflammatory biomarkers to evaluate the effect of Febuxostat on neuroinflammation and oxidative stress. The biomarkers include: Erythrocyte sedimentation rate (ESR) (mm/hr) |
| Change from baseline in Serum Interleukin-1 beta (IL-1β) at 3 months. | Baseline and 3 months | Blood samples will be analyzed to measure the change in levels of specific inflammatory biomarkers to evaluate the effect of Febuxostat on neuroinflammation and oxidative stress. The biomarkers include: Interleukin-1 beta (IL-1β) (pg/mL). |
| Change from baseline in Serum S100B protein at 3 months. | Baseline and 3 months | Blood samples will be analyzed to measure the change in levels of specific inflammatory biomarkers to evaluate the effect of Febuxostat on neuroinflammation and oxidative stress. The biomarkers include: Serum S100B protein (pg/mL). |
Countries
Egypt
Contacts
CONTACTMertihan E Elhadidi
Outcome results
None listed