Baricitinib for Respiratory Injury in Patients With Intracerebral Hemorrhage (BRIGHT)

Efficacy and Safety Study of Baricitinib for Respiratory Injury in Patients With Intracerebral Hemorrhage

This study is an investigator-initiated, prospective, randomized, open-label, blind end-point (PROBE) phase-2 clinical trial, to preliminarily evaluate the efficacy and safety of baritinib for the treatment of acute lung injury (ALI) after spontaneous intracerebral hemorrhage (ICH). Approximately 100 patients from different geographic sites across China will be recruited and randomized to 2 parallel arms in a 1:1 ratio to the intervention arm or control arm. The study will compare early additional baritinib 4-mg once daily (QD) administration to control arm with standardized treatments (background therapy), as novel agents for ALI in aimed subjects in immunological approach; and provide cortical evidence for further phase-3 clinical trials. The trial will be across up to approximately 15-month scope (12-month enrollment period and 3-month follow-up period). One independent Data and Safety Monitoring Board (DSMB) will actively monitor interim data in all stages to make recommendations about early study closure or changes to study protocol.

Study Overview

• Status: Completed
• Conditions: Intracerebral Hemorrhage; Acute Lung Injury(ALI)
• Intervention / Treatment: Drug: Baritinib

• Study Type: Interventional
• Enrollment (Actual): 110
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Chongqing
    • Chongqing, Chongqing, China, 400038
      • The Southwest Hospital of Army Medical University
  • Fujian
    • Fuzhou, Fujian, China, 350003
      • First Affiliated Hospital of Fujian Medical University
  • Jiangxi
    • Ganzhou, Jiangxi, China, 341000
      • First Affiliated Hospital of Gannan Medical University
    • Ganzhou, Jiangxi, China, 341000
      • Ganzhou People's Hospital
  • Shandong
    • Liaocheng, Shandong, China
      • Liaocheng People's Hospital, Liaocheng Brain Hospital
  • Tianjin
    • Tianjin, Tianjin, China
      • Tianjin Huanhu Hospital

Participation Criteria

Eligibility Criteria

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

Description

• Inclusion criteria

  1. Participant (or legally authorized representative) who gives informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in the protocol;
  2. Are male or female patients from 18 years of age (inclusive), at the time of enrollment;
  3. Have acute, spontaneous, primary, supratentorial intracerebral hemorrhage (ICH), confirmed by head CT scan, at the time of enrollment;
  4. Complicated with acute lung injury (ALI), confirmed by chest CT scan, at the time of enrollment.

• Exclusion criteria

  1. Have cerebellar or brainstem ICH;
  2. Have secondary ICH due to known or suspected structural abnormality in the brain, i.e., trauma, aneurysm, arteriovenous malformation, tumor;
  3. Have severe cerebral comorbidities, i.e., historical severe stroke, hydrocephalus, epilepsy;
  4. Have known advanced dementia or significant pre-stroke disability (modified Rankin Scale score of > 1);
  5. Have comorbidities might result in ALI, i.e., interstitial lung disease, chronic obstructive pulmonary disease, lung tumor, asthma, chronic respiratory failure, chronic heart failure;
  6. Have severe immunosuppression, defined as neutropenia (absolute neutrophil count < 1.0×10^9 cells/L) or lymphopenia (absolute lymphocyte count < 0.2×10^9 cells/L);
  7. Have chronic autoimmune disease, i.e., neuromyelitis optica spectrum disorders, multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus;

  8. Have ever received attenuated live vaccination or immunological treatments (see below) within 4 weeks prior to the enrollment, or intend to receive measures above;

     • Cytotoxic treatments: cyclophosphamide, methotrexate, sulfasalazine, leflunomide, etc.;
     • Biological treatments: adalimumab, infliximab, etanercept (TNF-α inhibitors), tocilizumab (anti-IL-6), secukinumab (anti-IL-17), etc.;
     • Baricitinib and other JAK inhibitors: tofacitinib, abrocitinib, etc.;
     • Other treatments: convalescent plasma or intravenous immunoglobulin (IVIg), corticosteroids with dosage over alternative purpose, etc.;
     • Note: Non-steroid anti-inflammatory drugs (NSAID) are allowed;
  9. Have current or historical infections within 2 weeks prior to the enrollment, i.e., pneumonia, SARS-CoV-2 infections, current active tuberculosis; or have ever received antibiotics within 2 weeks prior to the enrollment;
  10. Have contraindications for baricitinib, i.e., severe anemia (hemoglobulin < 80g/L), decompensated kidney disease (eGFR < 30mL/min/1.73m^2), or severe liver injury with alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 5 times ULN;
  11. Have a current diagnosis of active malignancy, history of deep vein thrombosis (DVT) and/or pulmonary embolism (PE) within 12 weeks prior to the enrollment or have a history of recurrent DVT/PE (≥ 2 times in total), which could constitute a risk when taking baricitinib in the opinion of the investigator;
  12. Are unlikely to finish the whole course of baricitinib administration in the opinion of the investigator (anticipated death or discharge);
  13. Are pregnant, or intend to become pregnant or breastfeed during the study;
  14. Are recruited for any other clinical trials;
  15. Are unsuitable for inclusion in the study in the opinion of the investigator.

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
No Intervention: Standard care; Standardized treatment for respiratory protection and/or ALI after ICH according to the related guidelines.
Experimental: Standard care plus Baricitinib; Besides standardized treatment (background therapy) for respiratory protection and/or ALI after ICH according to the related guidelines, participants will receive additional baritinib administration.	Drug: Baritinib; Participants will receive additional baritinib administration with 4-mg dosage once daily (QD) for consecutive 14 days after randomization (adjusted dosage of 2-mg QD for participants with eGFR between 30-60 mL/min/1.73m^2).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The score shift on the radiologic scoring system for lung injury involvement from baseline to day 14 after randomization	This radiologic scoring system for lung injury involvement was assessed with the chest CT scan, ranging from 0 to 10. The lower score indicated less lung injury while the higher represented more.	From baseline to day 14 after randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The modified Rankin Scale (mRS) score at day 90 after randomization	The mRS ranged from 0 to 6 and usually was adopted for neurological assessment. The lower score indicated favorable outcome while the higher represented worse or even death.	At day 90 after randomization
Time from randomization to the day of at least 1-point improvement on the National Institute of Allergy and Infectious Disease Ordinal Scale (NIAID-OS)	The NIAID-OS was for respiratory assessment, ranging from 1 to 8 in the original version. In this trial, the NIAID-OS was measured ranging from 3 to 8 (inclusive). The lower score indicated mild symptoms while the higher represented more critical or even death.	From randomization to the presence of clinical end-point (NIAID-OS improvement ≥ 1 point, discharge, or death) or the end of observation (up to 90 days after randomization), whichever comes first
Peripheral blood interleukin-6 (IL-6) level at day 14 after randomization		At day 14 after randomization
Peripheral blood interleukin-8 (IL-8) level at day 14 after randomization		At day 14 after randomization
Peripheral blood C-reactive protein (CRP) level at day 14 after randomization		At day 14 after randomization

Collaborators and Investigators

• Sponsor: De-zhi Kang
• Collaborators: Fujian Medical University; Tianjin Medical University General Hospital
• Investigators: Principal Investigator: De-zhi Kang, M.D., First Affiliated Hospital of Fujian Medical University; Study Director: Ying Fu, Ph.D., First Affiliated Hospital of Fujian Medical University

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2025
• Primary Completion (Actual): August 18, 2025
• Study Completion (Actual): August 18, 2025

Study Registration Dates

• First Submitted: December 10, 2024
• First Submitted That Met QC Criteria: December 16, 2024
• First Posted (Actual): December 17, 2024

Study Record Updates

• Last Update Posted (Actual): August 22, 2025
• Last Update Submitted That Met QC Criteria: August 21, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: Baricitinib; Acute Lung Injury; Intracerebral Hemorrhage
• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Intracranial Hemorrhages; Thoracic Injuries; Wounds and Injuries; Hemorrhage; Cerebral Hemorrhage; Lung Injury; Acute Lung Injury
• Other Study ID Numbers: MRCTA, ECFAH of FMU [2024] 556

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes