Baricitinib for the Lung Injury Following Spontaneous SAH (BLISS)

May 28, 2024 updated by: Tang-Du Hospital

The Treatment Effect of Baricitinib for the Secondary Pulmonary Complications Following Spontaneous Subarachnoid Hemorrhage

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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

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

Enrollment (Estimated)

100

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Sham Comparator: Control group
Participants will receive standard treatment and care according to the current management guidelines for SAH.
Other: Standard treatment
Participants will receive standard treatment and care according to the current management guidelines for subarachnoid hemorrhage.
Experimental: Baricitinib group
In addition to receiving standard treatment and care, baricitinib will be administrated orally (or crushed for nasogastric tube delivery) at a daily dosage of 4mg for three consecutive days following SAH.
Other: Standard treatment
Participants will receive standard treatment and care according to the current management guidelines for subarachnoid hemorrhage.
Drug: Baricitinib 4 MG
Baricitinib will be administered orally (or crushed for nasogastric tube delivery) at a daily dosage of 4mg for three consecutive days following SAH.
Other Names:
  • JAK Inhibitor

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The incidence of pneumonia
Time Frame: up to 14 days
Proportion of patients who occur pneumonia within 14 days
up to 14 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The incidence of ARDS
Time Frame: up to 14 days
The incidence of ARDS within 14 days following SAH.
up to 14 days
The incidence of other pulmonary complications
Time Frame: up to 14 days
The incidence of additional pulmonary complications, such as pulmonary edema, pulmonary embolism, and pleural effusion among patients within 14 days following SAH.
up to 14 days
The incidence of assisted ventilation measures
Time Frame: up to 14 days
The proportion of patients requiring assisted ventilation measures within 14 days following SAH.
up to 14 days
The incidence of Systemic Inflammatory Response Syndrome(SIRS)
Time Frame: up to 14 days
The incidence of SIRS within 14 days following SAH.
up to 14 days
Mortality rate
Time Frame: up to 90 days
The mortality rate within 14 days / 30 days / 90 days.
up to 90 days
The incidence of serious adverse events (SAE)
Time Frame: up to 14 days
The incidence of SAE within 14 days following SAH.
up to 14 days
The neurological functional outcome
Time Frame: up to 90 days
The neurological functional scores evaluated by Modified Rankin Scale and Glasgow Outcome Scale at 30 days and 90 days after SAH.
up to 90 days
The cognitive impairment after SAH
Time Frame: up to 90 days
The Mini-Mental Status Exam (MMSE) scores at 90 days after SAH.
up to 90 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Tang-Du Hospital

Investigators

  • Principal Investigator: Yan Qu, PhD MD, Department of Neurosurgery, Tangdu Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

August 1, 2024

Primary Completion (Estimated)

December 31, 2026

Study Completion (Estimated)

June 30, 2027

Study Registration Dates

First Submitted

May 28, 2024

First Submitted That Met QC Criteria

May 28, 2024

First Posted (Actual)

June 3, 2024

Study Record Updates

Last Update Posted (Actual)

June 3, 2024

Last Update Submitted That Met QC Criteria

May 28, 2024

Last Verified

May 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • BAR-SAH

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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