Clinical trial NCT06737705: Baricitinib for Respiratory Injury in Patients With Intracerebral Hemorrhage
Official title: Efficacy and Safety Study of Baricitinib for Respiratory Injury in Patients With Intracerebral Hemorrhage
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Intracerebral Hemorrhage
Acute Lung Injury(ALI)
Keywords: Intracerebral Hemorrhage
Acute Lung Injury
Baricitinib
Lead sponsor: First Affiliated Hospital of Fujian Medical University
Sponsor class: OTHER
Collaborators: name: Fujian Medical University
name: Tianjin Medical University General Hospital
First posted: 2024-12-17
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: * 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.

Primary outcomes:
measure: The score shift on the radiologic scoring system for lung injury involvement from baseline to day 14 after randomization
timeFrame: From baseline to day 14 after randomization
Secondary outcomes:
measure: The modified Rankin Scale (mRS) score at day 90 after randomization
timeFrame: At day 90 after randomization
measure: 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)
timeFrame: 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
measure: Peripheral blood interleukin-6 (IL-6) level at day 14 after randomization
timeFrame: At day 14 after randomization
measure: Peripheral blood interleukin-8 (IL-8) level at day 14 after randomization
timeFrame: At day 14 after randomization
measure: Peripheral blood C-reactive protein (CRP) level at day 14 after randomization
timeFrame: At day 14 after randomization
Other outcomes:
Locations:
city: Chongqing
country: China
facility: The Southwest Hospital of Army Medical University
state: Chongqing
city: Fuzhou
country: China
facility: First Affiliated Hospital of Fujian Medical University
state: Fujian
city: Ganzhou
country: China
facility: First Affiliated Hospital of Gannan Medical University
state: Jiangxi
city: Ganzhou
country: China
facility: Ganzhou People's Hospital
state: Jiangxi
city: Liaocheng
country: China
facility: Liaocheng People's Hospital, Liaocheng Brain Hospital
state: Shandong
city: Tianjin
country: China
facility: Tianjin Medical University General Hospital
state: Tianjin
city: Tianjin
country: China
facility: Tianjin Huanhu Hospital
state: Tianjin
Study officials:
affiliation: First Affiliated Hospital of Fujian Medical University
name: De-zhi Kang, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: First Affiliated Hospital of Fujian Medical University
name: Ying Fu, Ph.D.
role: STUDY_DIRECTOR
References: