Prophylactic Antibiotics in Admitted Cirrhotics

Phase 4

Completed

• Conditions: Cirrhosis, Liver
• Interventions: Drug: Normal saline; Drug: Ceftriaxone

• Registration Number: NCT04218695
• Lead Sponsor: Beth Israel Deaconess Medical Center

Brief Summary

In this pilot study, the investigators aim to assess feasibility of subject identification and data collection, including specimen processing, as well as the rate of enrollment for a future, larger study of the effect of empiric antibiotics for all patients with advanced cirrhosis admitted to the hospital without an existing indication for new antibiotic use. Specifically, the investigators will assess the incidence of infection after the time of enrollment and associated outcomes. Subjects will be randomly assigned to receive antibiotics vs placebo.

Detailed Description

Cirrhosis is associated with a state of immune-compromise and progressive decompensation, acute on chronic liver failure (ACLF), and death are often caused by bacterial infections. Different sub-groups of patients with cirrhosis at increased risk, i.e. active upper gastrointestinal hemorrhage, low protein ascites, history of spontaneous bacterial peritonitis (SBP), are known to benefit from prophylactic antibiotics. The investigators hypothesize that hospitalized patients with advanced cirrhosis are also at increased risk and thus may benefit from preventive treatment. Subjects will be randomly assigned to receive an antibiotic vs placebo.

Study Timeline

• Study First Submitted: 2020-01-02
• Study First Submitted QC: 2020-01-03
• Study First Posted: 2020-01-06
• Study Start: 2020-08-24
• Primary Completion: 2021-05-31
• Study Completion: 2021-08-28
• Results First Submitted: 2022-08-08
• Results First Submitted QC: 2022-08-08
• Results First Posted: 2022-08-31
• Status Verified: 2023-02
• Last Update Submitted: 2023-02-06
• Last Update Posted: 2023-03-03

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 32

Inclusion Criteria

• MELD-Na >= 18
• Cirrhosis as defined by liver biopsy or a composite assessment of available results from imaging, elastography, prior records, and laboratory studies

Exclusion Criteria

• Inability to obtain consent (from subject or next of kin/legal authorized representative (LAR)
• Allergy to cephalosporins
• Pregnancy (due to limited prospective data regarding safety of ceftriaxone)
• Existing indication for new antibiotics, e.g. upper gastrointestinal hemorrhage or apparent infection
• Use of major immunosuppressive medications (e.g. prednisone 20 mg/day or greater, immunosuppression for solid organ transplant)
• H/o recurrent C difficile infection within the past year (>2) or requiring fecal microbiota transplant (FMT)
• Enrollment in the study protocol during a previous admission

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Normal saline	Normal saline (50cc) once daily for up to one week or until end of hospitalization
Treatment	Ceftriaxone	1 gram intravenous ceftriaxone once daily for up to one week or until end of hospitalization

Primary Outcome Measures

Name	Time	Method
Infections	For 7 days or until end of hospital stay	Incident bacterial infection after enrollment

Secondary Outcome Measures

Name	Time	Method
Length of Stay	Up to 30 days	Days in hospital after randomization
Mortality	Up to 30 days	In-hospital
30-day Mortality	Up to 30-days	Includes f/u after discharge

Trial Locations

Locations (1)

Beth Israel Deaconess Medical Center; 🇺🇸 Boston, Massachusetts, United States