Baricitinib for the Lung Injury Following Spontaneous SAH

NCT06439615 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: BAR-SAH
• Study Type: interventional
• Target: 100
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Spontaneous Subarachnoid Hemorrhage

Keywords

Spontaneous subarachnoid hemorrhage; Baricitinib; Inflammation; Complications; Acute respiratory distress syndrome; Pneumonia; Outcome

Outcome Measures

Primary Outcomes (1)

• The incidence of pneumonia

  Proportion of patients who occur pneumonia within 14 days

  up to 14 days

Secondary Outcomes (8)

• The incidence of ARDS

  up to 14 days

• The incidence of other pulmonary complications

  up to 14 days

• The incidence of assisted ventilation measures

  up to 14 days

• The incidence of Systemic Inflammatory Response Syndrome(SIRS)

  up to 14 days

• Mortality rate

  up to 90 days

Study Arms (2)

Control group

SHAM COMPARATOR

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

Other: Standard treatment

Baricitinib group

EXPERIMENTAL

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.

Drug: Baricitinib 4 MG; Other: Standard treatment

Interventions

Baricitinib 4 MG DRUG

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

Also known as: JAK Inhibitor

Baricitinib group

Standard treatment OTHER

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

Baricitinib group; Control group

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 and ≤80 years old;
• Diagnosed with spontaneous subarachnoid hemorrhage through imaging or lumbar puncture;
• Hunt-Hess score of Ⅲ-Ⅳ;
• Acute onset, admitted to the hospital within 24 hours of onset

You may not qualify if:

• Presence of lung diseases before initiation of study treatment such as chronic obstructive emphysema, bronchiectasis, lung cancer, tuberculosis, or a history of lung surgery;
• 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;
• Secondary SAH (such as traumatic SAH), or combined craniocerebral trauma, intraparenchymal hemorrhage, or peripheral organ trauma;
• Evidence of fever or infection already present at the time of admission;
• 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;
• Presence of contraindications for baricitinib treatment, including severe liver damage, renal dysfunction (creatinine clearance rate \<30ml/min), hypercholesterolemia, or known drug allergies;
• Taking JAK inhibitors or other immunosuppressive drugs before the onset of the disease;
• Expected survival time less than 2 weeks;
• Females who are pregnant or breastfeeding;
• Currently participating in other interventional clinical studies;
• Patients who refuse to sign the consent form or refuse to accept follow-up.

Sponsors & Collaborators

• Tang-Du Hospital: lead

Related Publications (8)

• Robba C, Busl KM, Claassen J, Diringer MN, Helbok R, Park S, Rabinstein A, Treggiari M, Vergouwen MDI, Citerio G. Contemporary management of aneurysmal subarachnoid haemorrhage. An update for the intensivist. Intensive Care Med. 2024 May;50(5):646-664. doi: 10.1007/s00134-024-07387-7. Epub 2024 Apr 10.

  PMID: 38598130 BACKGROUND

• Chai CZ, Ho UC, Kuo LT. Systemic Inflammation after Aneurysmal Subarachnoid Hemorrhage. Int J Mol Sci. 2023 Jun 30;24(13):10943. doi: 10.3390/ijms241310943.

  PMID: 37446118 BACKGROUND

• Kahn JM, Caldwell EC, Deem S, Newell DW, Heckbert SR, Rubenfeld GD. Acute lung injury in patients with subarachnoid hemorrhage: incidence, risk factors, and outcome. Crit Care Med. 2006 Jan;34(1):196-202. doi: 10.1097/01.ccm.0000194540.44020.8e.

  PMID: 16374174 BACKGROUND

• Macmillan CS, Grant IS, Andrews PJ. Pulmonary and cardiac sequelae of subarachnoid haemorrhage: time for active management? Intensive Care Med. 2002 Aug;28(8):1012-23. doi: 10.1007/s00134-002-1382-7. Epub 2002 Jul 6.

  PMID: 12185419 BACKGROUND

• RECOVERY Collaborative Group. Baricitinib in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial and updated meta-analysis. Lancet. 2022 Jul 30;400(10349):359-368. doi: 10.1016/S0140-6736(22)01109-6.

  PMID: 35908569 BACKGROUND

• Taylor PC, Laedermann C, Alten R, Feist E, Choy E, Haladyj E, De La Torre I, Richette P, Finckh A, Tanaka Y. A JAK Inhibitor for Treatment of Rheumatoid Arthritis: The Baricitinib Experience. J Clin Med. 2023 Jul 6;12(13):4527. doi: 10.3390/jcm12134527.

  PMID: 37445562 BACKGROUND

• Ely EW, Ramanan AV, Kartman CE, de Bono S, Liao R, Piruzeli MLB, Goldman JD, Saraiva JFK, Chakladar S, Marconi VC; COV-BARRIER Study Group. Efficacy and safety of baricitinib plus standard of care for the treatment of critically ill hospitalised adults with COVID-19 on invasive mechanical ventilation or extracorporeal membrane oxygenation: an exploratory, randomised, placebo-controlled trial. Lancet Respir Med. 2022 Apr;10(4):327-336. doi: 10.1016/S2213-2600(22)00006-6. Epub 2022 Feb 3.

  PMID: 35123660 BACKGROUND

• Taylor PC, Keystone EC, van der Heijde D, Weinblatt ME, Del Carmen Morales L, Reyes Gonzaga J, Yakushin S, Ishii T, Emoto K, Beattie S, Arora V, Gaich C, Rooney T, Schlichting D, Macias WL, de Bono S, Tanaka Y. Baricitinib versus Placebo or Adalimumab in Rheumatoid Arthritis. N Engl J Med. 2017 Feb 16;376(7):652-662. doi: 10.1056/NEJMoa1608345.

  PMID: 28199814 BACKGROUND

MeSH Terms

Conditions

Subarachnoid Hemorrhage; Inflammation; Respiratory Distress Syndrome; Pneumonia

Interventions

baricitinib; Janus Kinase Inhibitors

Condition Hierarchy (Ancestors)

Intracranial Hemorrhages; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Lung Diseases; Respiratory Tract Diseases; Respiration Disorders; Respiratory Tract Infections; Infections

Intervention Hierarchy (Ancestors)

Protein Kinase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses

Study Officials

• Yan Qu, PhD MD

  Department of Neurosurgery, Tangdu Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Haixiao Liu, PhD MD

CONTACT

+86-02984778359; lhxiao@fmmu.edu.cn

Shunnan Ge, PhD MD

CONTACT

+86-02984778359; gesn8561@fmmu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 28, 2024
• First Posted: June 3, 2024
• Study Start: August 1, 2024
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): June 30, 2027
• Last Updated: June 3, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share