Mecobalamin Combined With Ceftriaxone Sodium in the Treatment of Sepsis Liver Injury

NCT06220929 | Unknown Phase 4

• 1 other identifier: CPan
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

The previous research of our research group shows that during the course of sepsis, the pyroptosis mediated by the caspase-4/GSDMD pathway in immune cells, induced by pathogens, is the main cause of immune collapse in sepsis patients. The preliminary study of this project further reveals that sepsis combined with intrahepatic cholestasis subsequently induces a rapid hepatocyte pyroptosis mediated by the Apaf-1 pyroptosome/caspase-3/GSDME signaling pathway. The interaction of these two processes triggers liver organ failure, suggesting GSDMD/GSDME as targets for the treatment of liver damage/liver failure in sepsis . Based on high-throughput drug screening and validation in in vivo and in vitro models, it was found that the combination of the old drug mecobalamin with ceftriaxone sodium, or with thiamine, used therapeutically, can block both of these cell pyroptosis pathways. Compared with corticosteroid drugs like dexamethasone and liver-protecting drugs, they have superior effects. Patients were randomly divided into intervention and control groups, with both groups receiving standard treatment and care for sepsis (decided by the attending physician). On this basis, the following treatments were administered: Control group (n=20): intravenous saline drip/oral placebo tablets; Intervention group (n=20): intravenous drip of ceftriaxone sodium 1g per dose, twice daily (continuously for 14 days), mecobalamin injection 1mg per dose, once daily (on days 1, 2, 3, 5, 7, 9, 11, 13), with a half-hour interval between medications. From day 15 to 28, take mecobalamin tablets orally, 1mg per dose, three times a day.

Conditions

Sepsis; Liver Dysfunction

Outcome Measures

Primary Outcomes (2)

• total bilirubin

  Total bilirubin reduced to 17.1 μmol/L

  28 days or when patient is discharged/dead

• bile acids

  Bile acids \<10 μmol/L

  28 days or when patient is discharged/dead

Study Arms (2)

Control group

SHAM COMPARATOR

Patients were randomly divided into intervention and control groups, with both groups receiving standard treatment and care for sepsis (decided by the attending physician). On this basis, the following treatments were administered: Control group (n=20): intravenous saline drip/oral placebo tablets.

Drug: Saline; Drug: Placebo

Intervention group

EXPERIMENTAL

Patients were randomly divided into intervention and control groups, with both groups receiving standard treatment and care for sepsis (decided by the attending physician). On this basis, the following treatments were administered: Intervention group (n=20): intravenous drip of ceftriaxone sodium 1g per dose, twice daily (continuously for 14 days), mecobalamin injection 1mg per dose, once daily (on days 1, 2, 3, 5, 7, 9, 11, 13), with a half-hour interval between medications. From day 15 to 28, take mecobalamin tablets orally, 1mg per dose, three times a day.

Drug: Mecobalamin; Drug: Ceftriaxone Sodium

Interventions

Ceftriaxone Sodium DRUG

Ceftriaxone sodium all intravenous formulations

Intervention group

Saline DRUG

The saline used in the control group was the same as the saline used in the experimental group to dispense the drug

Control group

Mecobalamin DRUG

The drug Mecobalamin in the intervention group was divided into intravenous and oral formulations, with the intravenous formulation being used for the first 14 days of the experiment and the oral formulation for the second 14 days.

Intervention group

Placebo DRUG

Placebo and Mecobalamin tablets look and smell the same.

Control group

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Mild to moderate sepsis as defined by the △SOFA score;
• Admission to ICU \<24 hours;
• Serum total bile acid concentration TBA ≥10μmol/L, total bilirubin concentration TBiL ≥17.1 μmol/L;
• Patients with suspected or confirmed infection as the main cause.-

You may not qualify if:

• Age \>85 years or \<18 years;
• Patients contraindicated for mecobalamin treatment, allergic to ceftriaxone sodium, or other contraindications;
• Existence of a potential disease with a life expectancy of \<1 year;
• Patients with non-infectious causes such as burns, trauma, chemical poisoning;
• Withdrawal of life support or anticipated life-threatening condition within 48 hours;
• History of autoimmune diseases, tumors, hepatobiliary diseases, diabetes, metabolic genetic diseases;
• Vitamin B deficiency, malnutrition history;
• Re-admission to ICU within one year;
• Relatives or guardians unwilling to participate in the study;
• Pregnancy.-

Sponsors & Collaborators

• Sichuan Provincial People's Hospital: lead

Study Sites (1)

Sichuan Provincial People's Hospital

Chengdu, Sichuan, China

Location

Related Publications (4)

• Lelubre C, Vincent JL. Mechanisms and treatment of organ failure in sepsis. Nat Rev Nephrol. 2018 Jul;14(7):417-427. doi: 10.1038/s41581-018-0005-7.

  PMID: 29691495 BACKGROUND

• He XL, Chen JY, Feng YL, Song P, Wong YK, Xie LL, Wang C, Zhang Q, Bai YM, Gao P, Luo P, Liu Q, Liao FL, Li ZJ, Jiang Y, Wang JG. Single-cell RNA sequencing deciphers the mechanism of sepsis-induced liver injury and the therapeutic effects of artesunate. Acta Pharmacol Sin. 2023 Sep;44(9):1801-1814. doi: 10.1038/s41401-023-01065-y. Epub 2023 Apr 11.

  PMID: 37041228 BACKGROUND

• Jiao C, Zhang H, Li H, Fu X, Lin Y, Cao C, Liu S, Liu Y, Li P. Caspase-3/GSDME mediated pyroptosis: A potential pathway for sepsis. Int Immunopharmacol. 2023 Nov;124(Pt B):111022. doi: 10.1016/j.intimp.2023.111022. Epub 2023 Oct 12.

  PMID: 37837715 BACKGROUND

• Pan C, Chen L, Lu C, Zhang W, Xia JA, Sklar MC, Du B, Brochard L, Qiu H. Lung Recruitability in COVID-19-associated Acute Respiratory Distress Syndrome: A Single-Center Observational Study. Am J Respir Crit Care Med. 2020 May 15;201(10):1294-1297. doi: 10.1164/rccm.202003-0527LE. No abstract available.

  PMID: 32200645 BACKGROUND

MeSH Terms

Conditions

Sepsis; Liver Diseases

Interventions

mecobalamin; Ceftriaxone; Sodium Chloride

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Cefotaxime; Cephacetrile; Cephalosporins; beta-Lactams; Lactams; Amides; Organic Chemicals; Thiazines; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Chun Pan, ph.D

  Sichuan Provincial People's Hospital

  STUDY DIRECTOR

Central Study Contacts

Sen Lu

CONTACT

13890741506; shenjun592021@163.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal investigater

Study Record Dates

• First Submitted: January 13, 2024
• First Posted: January 24, 2024
• Study Start: January 15, 2024
• Primary Completion: December 31, 2024
• Study Completion: January 1, 2025
• Last Updated: January 24, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)