Intracerebral Hemorrhage
Conditions
Keywords
Intracerebral Hemorrhage, Baricitinib
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 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.
Interventions
DRUGBaritinib
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).
Sponsors
De-zhi Kang
Fujian Medical University
Tianjin Medical University General Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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; *
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 pulmonary or cardiac disorders, 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Favorable neurological outcome defined by modified Rankin Scale (mRS) score of 0-2 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Favorable neurological outcome defined by mRS score of 0-3 | At day 90 after randomization | — |
| Shift analysis in the mRS score | At day 90 after randomization | — |
| Peripheral blood lymphocyte count | At days 7 and 14 after randomization | A key measure for immunosuppression. |
| New or exacerbated infection event | At days 7 and 14 after randomization | Infection is a clinical event, defined as an infection which is new or significantly exacerbated after randomization, adjudicated according to the modified CDC diagnostic criteria. |
| Hemorrhage progression event | At days 7 and 14 after randomization | Hemorrhage progression is a clinical event, including hematoma expansion or postoperative cerebral rebleeding after randomization, adjudicated with criteria of the hemorrhage growth \> 6 mL or 33%, and postoperative growth ≥ 5mL or significant morphological difference in CT scans. |
| Recurrent stroke event | At day 90 after randomization | A recurrent stroke is defined as an acute disturbance of focal neurologic function resulting in death or symptoms lasting more than 24 hours, including both ischemic and hemorrhagic stroke (excluding the index hemorrhage). |
| Mortality (death event) | At day 90 after randomization | Mortality (death event) accounted for all-cause and is verified with medical certification or social identification system. |
| Hierarchical composite event, including recurrent stroke and death | At day 90 after randomization | The hierarchical composite includes aforementioned long-term neurological events of recurrent stroke and death, which death was prioritized over recurrent stroke. |
| Peripheral blood exploratory biomarkers | At days 7 and 14 after randomization | Exploratory biomarkers for evaluating immunosuppression, expressed as changes from baseline |
| Serious adverse event (SAE) occurrence | At day 90 after randomization | Local-reported SAE is adjudicated if it meets the criteria according to ICH GCP E6 (R2) guideline. |
Countries
China
Contacts
PRINCIPAL_INVESTIGATORDe-zhi Kang, M.D.
First Affiliated Hospital of Fujian Medical University
STUDY_DIRECTORYing Fu, Ph.D.
First Affiliated Hospital of Fujian Medical University
Outcome results
None listed