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Baricitinib for Moderate and Severe Traumatic Intracerebral Hemorrhage/Contusions

Primary Purpose

Traumatic Brain Injury

Status
Not yet recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Baricitinib 4 MG
Standard treatment
Sponsored by
Tang-Du Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Traumatic Brain Injury focused on measuring traumatic intracerebral Hemorrhage, traumatic intracerebral Contusions, baricitinib, Janus kinase inhibitor, neuro-inflammatory responses

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept 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.

Sites / Locations

  • Tandu Hospital, Fourth Military Medical University

Arms of the Study

Arm 1

Arm 2

Arm Type

Sham Comparator

Experimental

Arm Label

Control group

Baricitinib group

Arm Description

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)

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.

Outcomes

Primary Outcome Measures

Clinical improvement
Glasgow Outcome Scale at 90 days, 180 days after brain trauma

Secondary Outcome Measures

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

Full Information

First Posted
July 4, 2023
Last Updated
September 26, 2023
Sponsor
Tang-Du Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT06065046
Brief Title
Baricitinib for Moderate and Severe Traumatic Intracerebral Hemorrhage/Contusions
Official Title
A Randomized Control Trial of Baricitinib Administration in Patients With Moderate and Severe Traumatic Intracerebral Hemorrhage/Contusions
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
October 2023 (Anticipated)
Primary Completion Date
July 2025 (Anticipated)
Study Completion Date
December 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Tang-Du Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Traumatic Brain Injury
Keywords
traumatic intracerebral Hemorrhage, traumatic intracerebral Contusions, baricitinib, Janus kinase inhibitor, neuro-inflammatory responses

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
Outcomes Assessor
Allocation
Randomized
Enrollment
100 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Control group
Arm Type
Sham Comparator
Arm Description
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)
Arm Title
Baricitinib group
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Baricitinib 4 MG
Other Intervention Name(s)
Baricitinib
Intervention Description
Baricitinib with be be administrated orally (or crushed for nasogastric tube delivery) and given daily at the dosage of 4mg for consecutive 14 days
Intervention Type
Other
Intervention Name(s)
Standard treatment
Other Intervention Name(s)
Blank control
Intervention Description
Patients will receive standard treatment and care according to the current management guidelines for traumatic brain injury.
Primary Outcome Measure Information:
Title
Clinical improvement
Description
Glasgow Outcome Scale at 90 days, 180 days after brain trauma
Time Frame
up to 180 days
Secondary Outcome Measure Information:
Title
Mortality rate
Description
In-hospital mortality rate, and mortality rate at 60 days, 180 days after brain trauma
Time Frame
up to 180 days
Title
Coma severity
Description
Glasgow Coma Scale at baseline, and at discharge
Time Frame
up to 2 weeks
Title
The rate of in-hospital secondary decompressive craniectomy
Description
The rate of patients undergo the decompressive craniectomy because of the intracranial hypertension refractory to medical treatment
Time Frame
up to 2 weeks
Title
Volume of edema around intracerebral hemorrhage/contusions
Description
Volume of edema around intracerebral hemorrhage/contusions at 3 days, 7days after brain trauma
Time Frame
up to 7 days
Title
Intracranial pressure
Description
The mean value of intracranial pressure at 2 to 7 days after brain trauma
Time Frame
up to 7 days
Title
The incidence of pneumonia
Description
The incidence of in-hospital pneumonia
Time Frame
up to 2 weeks
Title
The MMSE scores
Description
Mini-Mental State Examination (MMSE) scores at 60 days, 180 days after brain trauma
Time Frame
up to 180 days
Title
The MoCA scores
Description
Montreal Cognitive Assessment (MoCA) scores at 60 days, 180 days after brain trauma
Time Frame
up to 180 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Shunnan Ge, M.D,Ph.D
Phone
+8618165295569
Email
gesn8561@fmmu.edu.cn
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Yan Qu, M.D,Ph.D
Organizational Affiliation
Tang-Du Hospital
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Shunnan Ge, M.D,Ph.D
Organizational Affiliation
Tang-Du Hospital
Official's Role
Study Director
Facility Information:
Facility Name
Tandu Hospital, Fourth Military Medical University
City
Xi'an
State/Province
Shaanxi
ZIP/Postal Code
710038
Country
China
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Shunnan Ge, M.D Ph.D
Phone
+86 18165295569
Email
gesn8561@fmmu.edu.cn
First Name & Middle Initial & Last Name & Degree
Yan Qu, M.D,Ph.D
First Name & Middle Initial & Last Name & Degree
Shunnan Ge, M.D,Ph.D

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
32999392
Citation
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.
Results Reference
background
PubMed Identifier
32542785
Citation
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.
Results Reference
background
PubMed Identifier
28199814
Citation
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.
Results Reference
background
PubMed Identifier
23924471
Citation
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.
Results Reference
background
PubMed Identifier
36429017
Citation
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.
Results Reference
background
PubMed Identifier
35507486
Citation
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.
Results Reference
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PubMed Identifier
34480861
Citation
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. Erratum In: Lancet Respir Med. 2021 Oct;9(10):e102.
Results Reference
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Baricitinib for Moderate and Severe Traumatic Intracerebral Hemorrhage/Contusions

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