Prophylactic Antibiotics in Admitted Cirrhotics

A Pilot Study of the Effect of Prophylactic Antibiotics on Hospitalized Patients With Advanced Cirrhosis

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.

Study Overview

• Status: Completed
• Conditions: Cirrhosis, Liver
• Intervention / Treatment: Drug: Ceftriaxone; Drug: Normal saline

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 Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment; 1 gram intravenous ceftriaxone once daily for up to one week or until end of hospitalization	Drug: Ceftriaxone; Antibiotic; Other Names: Rocephin
Placebo Comparator: Placebo; Normal saline (50cc) once daily for up to one week or until end of hospitalization	Drug: Normal saline; 50cc intravenous once daily; Other Names: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Infections	Incident bacterial infection after enrollment	For 7 days or until end of hospital stay

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Length of Stay	Days in hospital after randomization	Up to 30 days
Mortality	In-hospital	Up to 30 days
30-day Mortality	Includes f/u after discharge	Up to 30-days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incident C Difficile Colitis	Positive stool toxin/PCR with new onset diarrhea	30 days
Incident ACLF	(by NACSELD) or change in CLIF-C ACLF score	During hospital admission up to 30 days
Incident Variceal Hemorrhage	Incident variceal hemorrhage	During hospital admission up to 30 days
Increase in MELD-Na	>2 pts	Upon discharge (or at 30 days)
Fungal Infection	Incident fungal infection (by culture data or requirement for new anti-fungal medication)	During hospital admission up to 30 days
Biomarker of Infection	Procalcitonin	Once at time of randomization
Biomarker of Infection	C-reactive protein	Once at time of randomization

Collaborators and Investigators

• Sponsor: Beth Israel Deaconess Medical Center
• Collaborators: American Association for the Study of Liver Diseases Foundation
• Investigators: Principal Investigator: Zachary P Fricker, MD, Beth Israel Deaconess Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): August 24, 2020
• Primary Completion (Actual): May 31, 2021
• Study Completion (Actual): August 28, 2021

Study Registration Dates

• First Submitted: January 2, 2020
• First Submitted That Met QC Criteria: January 3, 2020
• First Posted (Actual): January 6, 2020

Study Record Updates

• Last Update Posted (Actual): March 3, 2023
• Last Update Submitted That Met QC Criteria: February 6, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Liver Diseases; Fibrosis; Liver Cirrhosis; Anti-Infective Agents; Anti-Bacterial Agents; Ceftriaxone
• Other Study ID Numbers: 2020P000050; BIDMC-ABX-pilot-19 (Other Identifier: Beth Israel Deaconess Medical Center)

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