Prophylactic Antibiotics in Admitted Cirrhotics

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Cirrhosis, Liver

Intervention / Treatment
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* Drug: Ceftriaxone
* Drug: Normal saline


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

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

What is the study measuring?
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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 |