Efficacy and Safety Study of Baricitinib for Patients With Intracerebral Hemorrhage
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 110
- 试验地点
- 6
- 主要终点
- The score shift on the radiologic scoring system for lung injury involvement from baseline to day 14 after randomization
研究概览
简要总结
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 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 ICH 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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Inclusion criteria
- •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;
- •Are male or female patients from 18 years of age (inclusive), at the time of enrollment;
- •Have acute, spontaneous, primary, supratentorial intracerebral hemorrhage (ICH), confirmed by head CT scan, at the time of enrollment;
排除标准
- •Have cerebellar or brainstem ICH;
- •Have secondary ICH due to known or suspected structural abnormality in the brain, i.e., trauma, aneurysm, arteriovenous malformation, tumor;
- •Have severe cerebral comorbidities, i.e., historical severe stroke, hydrocephalus, epilepsy;
- •Have known advanced dementia or significant pre-stroke disability (modified Rankin Scale score of > 1);
- •Have comorbidities might result in pulmonary or cardiac disorders, i.e., interstitial lung disease, chronic obstructive pulmonary disease, lung tumor, asthma, chronic respiratory failure, chronic heart failure;
- •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);
- •Have chronic autoimmune disease, i.e., neuromyelitis optica spectrum disorders, multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus;
- •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;
- •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;
- •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;
- •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;
- •Are unlikely to finish the whole course of baricitinib administration in the opinion of the investigator (anticipated death or discharge);
- •Are pregnant, or intend to become pregnant or breastfeed during the study;
- •Are recruited for any other clinical trials;
- •Are unsuitable for inclusion in the study in the opinion of the investigator.
研究组 & 干预措施
Standard care plus Baricitinib
Besides standardized treatment (background therapy) for ICH according to the related guidelines, participants will receive additional baritinib administration.
干预措施: Baritinib (Drug)
结局指标
主要结局
The score shift on the radiologic scoring system for lung injury involvement from baseline to day 14 after randomization
时间窗: 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.
次要结局
- The modified Rankin Scale (mRS) score at day 90 after randomization(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)(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)
研究者
De-zhi Kang
Prof.
First Affiliated Hospital of Fujian Medical University