Baricitinib for Moderate and Severe Traumatic Intracerebral Hemorrhage/Contusions

Phase 2

Recruiting

• Conditions: Traumatic Brain Injury
• Interventions: Other: Standard treatment; Drug: Baricitinib 4 MG

• Registration Number: NCT06065046
• Lead Sponsor: Tang-Du Hospital

Brief Summary

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.

Detailed Description

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.

Study Timeline

• Study First Submitted: 2023-07-04
• Study First Submitted QC: 2023-09-26
• Study First Posted: 2023-10-03
• Study Start: 2023-11-24
• Status Verified: 2025-06
• Last Update Submitted: 2025-06-01
• Last Update Posted: 2025-06-04
• Primary Completion: 2026-06-30
• Study Completion: 2026-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 100

Inclusion Criteria

1. Age 18 years older and younger than 80 years old.
2. Definite history of traumatic brain injury.
3. Admission within≤24 hours after the traumatic brain injury.
4. CT scans demonstrate intracerebral hemorrhage/contusions with and without extracerebral hemorrhage (epi- and sub- dural hemorrhage)
5. GCS score of 5 or greater and no more than 12 at time of enrollment.
6. Closed head injury.
7. Admission without infections
8. Signed and dated informed consent by the subject, legally authorized representative, or surrogate obtained.

Exclusion Criteria

1. Time of head injury cannot be reliably assessed.
2. Subjects is considered a candidate for immediate surgical intervention because of severe extracranial injury.
3. Open head injury.
4. Pregnancy or parturition within previous 30 days or active lactation.
5. Use of Janus kinase inhibitors (baricinitib,abroctinib, AG490 and etc.)
6. Pre-traumatic dementia or disability.
7. With severe liver, kidney disease, or malignancy, life expectancy is less than 14 days.
8. Severe pulmonary infection.
9. Severe or acute heart failure.
10. Severe infections within previous 30 days.
11. History of myocardial infarction.
12. Known sensitivity to baricinitib.
13. Severe decreases in neutrophil, lymphocyte and platelet counts, severe decrease in hemoglobin.
14. Severe liver and kidney dysfunction.
15. Currently participating in other interventional clinical trials.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Control group	Standard treatment	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)
Baricitinib group	Baricitinib 4 MG	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.

Primary Outcome Measures

Name	Time	Method
Clinical improvement	up to 180 days	Glasgow Outcome Scale at 180 days after brain trauma

Secondary Outcome Measures

Name	Time	Method
Glasgow Outcome Scale	up to 90 days	The Glasgow Outcome Scale at 90 days after brain trauma
Serum inflammatory factors	up to 7 days	The levels of serum inflammatory factors TNF-α、IFN-γ、IL-1β、IL-6、IL-8 at 2 to 7days after brain trauma
Volume of edema around intracerebral hemorrhage/contusions	up to 7 days	Volume of edema around intracerebral hemorrhage/contusions at 2 to 7days after brain trauma
Intracranial pressure	up to 7 days	The mean value of intracranial pressure at 2 to 7 days after brain trauma
The incidence of pneumonia	up to 2 weeks	The incidence of in-hospital pneumonia
Mortality rate	up to 180 days	In-hospital mortality rate, and mortality rate at 90 days, 180 days after brain trauma
Coma severity	up to 2 weeks	Glasgow Coma Scale at baseline, and at discharge

Trial Locations

Locations (1)

Tandu Hospital, Fourth Military Medical University; 🇨🇳 Xi'an, Shaanxi, China