Baricitinib for the Lung Injury Following Spontaneous SAH

Phase 2Not Yet RecruitingNCT06439615

Tang-Du Hospital100 enrolled

Overview

The present study is a randomized, parallel control, and double-blind trial designed to assess the efficacy of baricitinib in reducing the occurrence of pulmonary complications in patients with spontaneous subarachnoid hemorrhage (SAH). The research protocol incorporates an adaptive design, allowing for modifications to key elements such as the sample size enrolled during interim analysis.

Subarachnoid hemorrhage (SAH) is an acute cerebrovascular disorder resulting from the rupture of intracranial vessels, primarily caused by factors such as the rupture of intracranial aneurysms (accounting for approximately 75%-80% of SAH cases), arteriovenous malformations, and abnormal vasculature. Pulmonary complications, including pneumonia and acute respiratory distress syndrome (ARDS), frequently manifest in a significant number of subarachnoid hemorrhage (SAH) patients, significantly impacting their prognosis. The pathogenesis of these complications can be partially attributed to an exaggerated inflammatory response during the acute phase following SAH. The incidence of cerebrovascular spasm and mortality rates significantly increase in SAH patients with pulmonary complications, thereby resulting in a poorer long-term prognosis. However, the current strategy for preventing or managing pulmonary complications after SAH is not sufficiently effective. The JAK-STAT signaling pathway, a pivotal stress-induced inflammatory cascade triggered subsequent to SAH, is characterized by its rapid response to external stimuli. Baricitinib, a JAK inhibitor developed by Eli Lilly Company, exerts significant anti-inflammatory effects in diverse pathological processes and finds extensive application in patients with rheumatoid arthritis, COVID-19, and alopecia areata. However, it remains uncertain whether early administration of baricitinib can mitigate the incidence of secondary pulmonary complications and enhance the prognosis of SAH by suppressing the exaggerated inflammatory response during the acute phase following SAH. The current multicenter clinical trial is designed as a randomized, parallel control, and double-blind study to assess the efficacy of baricitinib in reducing pulmonary complications among patients with SAH. SAH Patients admitted to participating clinical centers with a Hunt-Hess score of Ⅲ-Ⅳ will undergo continuous screening based on predefined selection criteria. The enrolled subjects will be randomly allocated into an experimental group and a control group, receiving either Baricitinib (4mg/day for 3 days) in addition to conventional treatment or placebo in addition to conventional treatment, respectively. The primary outcome is the incidence of pneumonia within 14 days after SAH. While the secondary outcome including the incidence of ARDS and other pulmonary complications within 14 days, the incidence of serious adverse events within 14 days, the proportion of patients requiring assisted ventilation measures within 14 days, the mortality rate within 14/30/90 days, as well as the neurological outcome at 30/90 days.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

DOUBLE

Enrollment

100

Conditions

Spontaneous Subarachnoid Hemorrhage

Interventions

Baricitinib 4 MGDRUG

Baricitinib will be administered orally (or crushed for nasogastric tube delivery) at a daily dosage of 4mg for three consecutive days following SAH.

Standard treatmentOTHER

Participants will receive standard treatment and care according to the current management guidelines for subarachnoid hemorrhage.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 80 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Age ≥18 and ≤80 years old; 2. Diagnosed with spontaneous subarachnoid hemorrhage through imaging or lumbar puncture; 3. Hunt-Hess score of Ⅲ-Ⅳ; 4. Acute onset, admitted to the hospital within 24 hours of onset Exclusion Criteria: 1. Presence of lung diseases before initiation of study treatment such as chronic obstructive emphysema, bronchiectasis, lung cancer, tuberculosis, or a history of lung surgery; 2. Presence of autoimmune diseases, immune system dysfunction, or blood system dysfunction (absolute lymphocyte count (ALC) less than 0.5×109 cells/L, absolute neutrophil count (ANC) less than 1×109 cells/L, or hemoglobin value less than 8 g/dL) before the onset of the disease; 3. Secondary SAH (such as traumatic SAH), or combined craniocerebral trauma, intraparenchymal hemorrhage, or peripheral organ trauma; 4. Evidence of fever or infection already present at the time of admission; 5. History of previous craniocerebral surgery, previous cerebral hemorrhage, craniocerebral injury, cerebral infarction, intracranial tumor, or presence of neurological dysfunction before the onset of the disease; 6. Presence of contraindications for baricitinib treatment, including severe liver damage, renal dysfunction (creatinine clearance rate \<30ml/min), hypercholesterolemia, or known drug allergies; 7. Taking JAK inhibitors or other immunosuppressive drugs before the onset of the disease; 8. Expected survival time less than 2 weeks; 9. Females who are pregnant or breastfeeding; 10. Currently participating in other interventional clinical studies; 11. Patients who refuse to sign the consent form or refuse to accept follow-up.

Outcomes

Primary Outcomes

The incidence of pneumonia

Proportion of patients who occur pneumonia within 14 days

Time frame: up to 14 days

Secondary Outcomes

The incidence of ARDS

The incidence of ARDS within 14 days following SAH.

Time frame: up to 14 days

The incidence of other pulmonary complications

The incidence of additional pulmonary complications, such as pulmonary edema, pulmonary embolism, and pleural effusion among patients within 14 days following SAH.

Time frame: up to 14 days

The incidence of assisted ventilation measures

The proportion of patients requiring assisted ventilation measures within 14 days following SAH.

Time frame: up to 14 days

The incidence of Systemic Inflammatory Response Syndrome(SIRS)

The incidence of SIRS within 14 days following SAH.

Time frame: up to 14 days

Mortality rate

The mortality rate within 14 days / 30 days / 90 days.

Time frame: up to 90 days

The incidence of serious adverse events (SAE)

The incidence of SAE within 14 days following SAH.

Time frame: up to 14 days

The neurological functional outcome

The neurological functional scores evaluated by Modified Rankin Scale and Glasgow Outcome Scale at 30 days and 90 days after SAH.

Central Contacts

Haixiao Liu, PhD MD

CONTACT

+86-02984778359 lhxiao@fmmu.edu.cn

Shunnan Ge, PhD MD

CONTACT

+86-02984778359 gesn8561@fmmu.edu.cn

Data from ClinicalTrials.gov

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