Baricitinib for Moderate and Severe Traumatic Intracerebral Hemorrhage/Contusions

Sponsor

Tang-Du Hospital (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT06065046

Collaborator

(none)

100

Enrollment

Location

Arms

Anticipated Duration (Months)

3.8

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Traumatic Brain Injury	Drug: Baricitinib 4 MG Other: Standard treatment	Phase 2

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 90 days, 180 days after brain trauma. And the secondary outcome including In-hospital mortality rate, and mortality rate at 60 days, 180 days after brain trauma; Glasgow Coma Scale at discharge;The rate of patients undergo the decompressive craniectomy because of the intracranial hypertension refractory to medical treatment;Volume of edema around intracerebral hemorrhage/contusions at 3 days, 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 Design

Study Type:

Interventional

Anticipated Enrollment :

100 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

A Randomized Control Trial of Baricitinib Administration in Patients With Moderate and Severe Traumatic Intracerebral Hemorrhage/Contusions

Anticipated Study Start Date :

Oct 1, 2023

Anticipated Primary Completion Date :

Jul 1, 2025

Anticipated Study Completion Date :

Dec 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Sham Comparator: 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)	Other: Standard treatment Patients will receive standard treatment and care according to the current management guidelines for traumatic brain injury. Other Names: Blank control
Experimental: 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.	Drug: Baricitinib 4 MG Baricitinib with be be administrated orally (or crushed for nasogastric tube delivery) and given daily at the dosage of 4mg for consecutive 14 days Other Names: Baricitinib

Arm

Intervention/Treatment

Sham Comparator: 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)

Other: Standard treatment

Patients will receive standard treatment and care according to the current management guidelines for traumatic brain injury.

Other Names:

Blank control

Experimental: 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.

Drug: Baricitinib 4 MG

Baricitinib with be be administrated orally (or crushed for nasogastric tube delivery) and given daily at the dosage of 4mg for consecutive 14 days

Other Names:

Baricitinib

Outcome Measures

Primary Outcome Measures

Clinical improvement [up to 180 days]
Glasgow Outcome Scale at 90 days, 180 days after brain trauma

Secondary Outcome Measures

Mortality rate [up to 180 days]
In-hospital mortality rate, and mortality rate at 60 days, 180 days after brain trauma
Coma severity [up to 2 weeks]
Glasgow Coma Scale at baseline, and at discharge
The rate of in-hospital secondary decompressive craniectomy [up to 2 weeks]
The rate of patients undergo the decompressive craniectomy because of the intracranial hypertension refractory to medical treatment
Volume of edema around intracerebral hemorrhage/contusions [up to 7 days]
Volume of edema around intracerebral hemorrhage/contusions at 3 days, 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
The MMSE scores [up to 180 days]
Mini-Mental State Examination (MMSE) scores at 60 days, 180 days after brain trauma
The MoCA scores [up to 180 days]
Montreal Cognitive Assessment (MoCA) scores at 60 days, 180 days after brain trauma

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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.

Exclusion Criteria:

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.