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

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

Interventions

DRUG

Mecobalamin

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.

DRUG

Ceftriaxone Sodium

Ceftriaxone sodium all intravenous formulations

DRUG

Saline

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

DRUG

Placebo

Placebo and Mecobalamin tablets look and smell the same.

Sponsors & Collaborators

• Sichuan Provincial People's Hospital

  lead OTHER

Principal Investigators

• Chun Pan, ph.D · Sichuan Provincial People's Hospital

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

85 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2024-01-15

Primary Completion

2024-12-31

Completion

2025-01-01

Countries

• China

Study Locations