Baricitinib for Moderate and Severe Traumatic Intracerebral Hemorrhage/Contusions

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

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.

Study Overview

• Status: Recruiting
• Conditions: Traumatic Brain Injury
• Intervention / Treatment: Other: Standard treatment; Drug: Baricitinib 4 MG

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 Type: Interventional
• Enrollment (Estimated): 100
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Shunnan Ge, M.D,Ph.D; Phone Number: +8618165295569; Email: gesn8561@fmmu.edu.cn

Study Locations

• China
  • Shaanxi
    • Xi'an, Shaanxi, China, 710038
      • Recruiting
      • Tandu Hospital, Fourth Military Medical University
      • Contact: Shunnan Ge, M.D Ph.D; Phone Number: +86 18165295569; Email: gesn8561@fmmu.edu.cn
      • Principal Investigator: Yan Qu, M.D,Ph.D
      • Sub-Investigator: Shunnan Ge, M.D,Ph.D

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical improvement	Glasgow Outcome Scale at 180 days after brain trauma	up to 180 days

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Tang-Du Hospital
• Collaborators: Second Affiliated Hospital of Xi'an Jiaotong University; Weinan Central Hospital; First People's Hospital of Xianyang; GEM Flower Xian Changqing Staff Hospital; The First Hospital of Yulin; Qianxian People's Hospital; Chongqing Hospital of PAP; Xidian Group Hospital; Chongqing University Central Hospital & Chongqing Emergency Medical Center; The People's Hospital of Jiaozuo City; The 987th Hospital of the Joint Logistics Support Force of the People's Liberation Army of China; Baoji Fengxiang District Hospital
• Investigators: Study Chair: Yan Qu, M.D,Ph.D, Tang-Du Hospital; Study Director: Shunnan Ge, M.D,Ph.D, Tang-Du Hospital

Publications and helpful links

General Publications

• Taylor PC, Keystone EC, van der Heijde D, Weinblatt ME, Del Carmen Morales L, Reyes Gonzaga J, Yakushin S, Ishii T, Emoto K, Beattie S, Arora V, Gaich C, Rooney T, Schlichting D, Macias WL, de Bono S, Tanaka Y. Baricitinib versus Placebo or Adalimumab in Rheumatoid Arthritis. N Engl J Med. 2017 Feb 16;376(7):652-662. doi: 10.1056/NEJMoa1608345.
• Begemann M, Leon M, van der Horn HJ, van der Naalt J, Sommer I. Drugs with anti-inflammatory effects to improve outcome of traumatic brain injury: a meta-analysis. Sci Rep. 2020 Sep 30;10(1):16179. doi: 10.1038/s41598-020-73227-5.
• Jorgensen SCJ, Tse CLY, Burry L, Dresser LD. Baricitinib: A Review of Pharmacology, Safety, and Emerging Clinical Experience in COVID-19. Pharmacotherapy. 2020 Aug;40(8):843-856. doi: 10.1002/phar.2438. Epub 2020 Jul 27.
• DU AL, Ji TL, Yang B, Cao JF, Zhang XG, Li Y, Pan S, Zhang B, Hu ZB, Zeng XW. Neuroprotective effect of AG490 in experimental traumatic brain injury of rats. Chin Med J (Engl). 2013;126(15):2934-7.
• Li T, Li L, Peng R, Hao H, Zhang H, Gao Y, Wang C, Li F, Liu X, Chen F, Zhang S, Zhang J. Abrocitinib Attenuates Microglia-Mediated Neuroinflammation after Traumatic Brain Injury via Inhibiting the JAK1/STAT1/NF-kappaB Pathway. Cells. 2022 Nov 13;11(22):3588. doi: 10.3390/cells11223588.
• Messenger A, Harries M. Baricitinib in Alopecia Areata. N Engl J Med. 2022 May 5;386(18):1751-1752. doi: 10.1056/NEJMe2203440. No abstract available.
• Marconi VC, Ramanan AV, de Bono S, Kartman CE, Krishnan V, Liao R, Piruzeli MLB, Goldman JD, Alatorre-Alexander J, de Cassia Pellegrini R, Estrada V, Som M, Cardoso A, Chakladar S, Crowe B, Reis P, Zhang X, Adams DH, Ely EW; COV-BARRIER Study Group. Efficacy and safety of baricitinib for the treatment of hospitalised adults with COVID-19 (COV-BARRIER): a randomised, double-blind, parallel-group, placebo-controlled phase 3 trial. Lancet Respir Med. 2021 Dec;9(12):1407-1418. doi: 10.1016/S2213-2600(21)00331-3. Epub 2021 Sep 1.

Study record dates

Study Major Dates

• Study Start (Actual): November 24, 2023
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: July 4, 2023
• First Submitted That Met QC Criteria: September 26, 2023
• First Posted (Actual): October 3, 2023

Study Record Updates

• Last Update Posted (Actual): April 13, 2026
• Last Update Submitted That Met QC Criteria: April 7, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: baricitinib; Janus kinase inhibitor; traumatic intracerebral Hemorrhage; traumatic intracerebral Contusions; neuro-inflammatory responses
• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Wounds and Injuries; Craniocerebral Trauma; Trauma, Nervous System; Intracranial Hemorrhages; Intracranial Hemorrhage, Traumatic; Brain Injuries; Cerebral Hemorrhage; Brain Hemorrhage, Traumatic; Brain Injuries, Traumatic; Cerebral Hemorrhage, Traumatic; baricitinib
• Other Study ID Numbers: TDSJWK-TBI-Baritinib

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No