Clinical trial NCT04218695
Conditions: Cirrhosis, Liver
Sponsor: Beth Israel Deaconess Medical Center
Start date: 2020-08-24; Completion date: 2021-08-28
Enrollment: 32 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

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.

Arms: arm 1: 1 gram intravenous ceftriaxone once daily for up to one week or until end of hospitalization arm 2: Normal saline (50cc) once daily for up to one week or until end of hospitalization
Interventions: intervention 1: Ceftriaxone intervention 2: Normal saline
Intervention descriptions: intervention 1: Antibiotic intervention 2: 50cc intravenous once daily

Protocol documents:
Prot_SAP_000.pdf: 
NCT Number:  
NCT04218695 
Official Title: 
A Pilot Study of the Effect of Prophylactic Antibiotics on Hospitalized 
Patients With Advanced Cirrhosis 
Document Type: 
Protocol with SAP 
Document Date: 
2/24/2021 


(CCI) Committee on Clinical Investigations 
Page 1 of 11 
 
Study Description – Part B 
CCI Form:  9-2015 
 
PI Revision Date:  2/24/2021  
 
PART B 
STUDY DESCRIPTION 
 
TITLE OF PROTOCOL 
A pilot study of the effect of prophylactic antibiotics on 
hospitalized patients with advanced cirrhosis   
Principal Investigator 
Zachary Fricker, MD  
 
B1. 
PURPOSE OF PROTOCOL 
 
In this pilot study, we aim to assess feasibility of subject identification and data 
collection, including specimen processing, as well as the rate of enrollment for a future, larger 
randomized, placebo controlled trial of the effect of prophylactic antibiotics for all patients 
with advanced cirrhosis admitted to the hospital without an existing indication for new 
antibiotic use. Specifically, we will assess the incidence of infection after the time of 
enrollment and associated outcomes. 
 
 
B2. 
SIGNIFICANCE AND BACKGROUND FOR THE STUDY 
Advanced chronic liver disease/cirrhosis creates a state of relative immune-
compromise, and, indeed, infections are a key precipitant of clinical decline in patients with 
cirrhosis. Specifically, infections of any kind are a common cause of acute on chronic liver 
failure (ACLF) and complicate 20-40% of hospital admissions of patients with cirrhosis. 
Although other pathogens are also important, the vast majority of infections in patients with 
cirrhosis are of bacterial origin. In other high-risk hospitalized patient populations, early 
initiation of antibiotics has been shown to reduce the need for intensive care unit (ICU) 
admission and short-term mortality. Unfortunately, the presentation of infection in patients 
with cirrhosis is protean and may be subtle. Diagnosis may be delayed by the absence of 
classic signs of infection such as fever and absolute leukocytosis. Vital diagnostic studies, 
such as paracentesis or other culture (blood, urine, or sputum) may be delayed or may not 
yield results until days after presentation. Delaying antibiotics until such studies result is 
inadvisable in patients with infection; however, empiric administration of antibiotics to all 
patients with cirrhosis admitted to the hospital would result in waste and increased risk of 
antibiotic resistance, Clostridium difficile infection, and other adverse effects. Sub-groups of 
patients with cirrhosis are already known to benefit from empiric/prophylactic antibiotics 
including those with acute upper gastrointestinal hemorrhage and those with increased risk of 
spontaneous bacterial peritonitis. The risk of infection increases with more advanced 
cirrhosis, as marked by higher Model for End-stage Liver Disease – Sodium (MELD-Na).  
There are also biomarkers of systemic infection that, although not specific, may be 
used to identify patients more likely to have an active infection and thus allow more targeted 
use of empiric antibiotics. Specifically, increase in serum C-reactive protein (CRP, >25 mg/L) 
and Procalcitonin (>0.5 ng/mL) are associated with acute bacterial infection.  
These factors may permit identification of patients who would benefit from 
prophylactic/empiric antibiotics. There has not, however, been investigation of the effect of 
prophylactic antibiotics on hospitalized patients with advanced cirrhosis beyond the sub-
populations described above.  
 


(CCI) Committee on Clinical Investigations 
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Study Description – Part B 
CCI Form:  9-2015 
 
PI Revision Date:  2/24/2021  
 
 
B3. 
DESCRIPTION OF RESEARCH PROTOCOL 
A. 
Study Design – Overview, Methods, Procedures 
 
This is a blinded, randomized, placebo-controlled pilot trial to determine feasibility of 
subject identification, rate of enrollment, and data collection, including specimen processing, 
for a future, larger randomized trial 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, we will assess the incidence of infection after the time of enrollment and 
associated outcomes. Patients will be randomized to receive either ceftriaxone or placebo 
(normal saline). Study drug will be delivered in masked vials for daily IV administration. 
Case finding and Screening: Eligible patients will be identified in the emergency 
department or by admitting physicians upon their initial medical assessment or by study 
personnel via daily review of the inpatient hepatology ward and consultative service census. 
Study personnel will screen each potential subject by review of medical record for potential 
eligibility.  
Consent: If a patient meets basic eligibility criteria, a study investigator will meet with 
the potential subject/LAR to review the study protocol and obtain informed consent. 
Screening measures will be completed following consent and the balance of the baseline 
measures will be completed.   
Extended Screening/Baseline: Evaluation for undiagnosed infection will be 
completed following consent and prior to randomization including: chest x-ray, venous blood 
culture, urine culture- all, if not already performed via routine care. These studies may be 
deferred if they have been done within 7 days of enrollment and there has been no change in 
clinical status. Subjects with infection identified upon enrollment will be excluded from further 
participation and have further treatment directed by their standard clinical providers.  
Each subject’s medical record will be reviewed to determine the presence or absence 
of diuretic-resistant ascites (defined by history of TIPS, large volume paracentesis within the 
past 3 months despite diuretics, or intolerance of diuretics).  
Each subject’s medical record will be reviewed to determine the calculated baseline 
CLIF-C ACLF score (Chronic Liver Failure Consortium (CLIF-C) Acute on Chronic Liver 
Failure). This will be computed using data (laboratory and physical examination) collected as 
part of standard of care. These data points include: 
 bilirubin,  
 creatinine,  
 INR,  
 West Haven grade of encephalopathy,  
 mean arterial pressure, and  
 peripheral oxygen saturation (SpO2).  
A peripheral or central venous blood sample will be taken after consent is obtained. 
Approximately thirty milliliters (2 tablespoons) of whole blood will be collected.  We will 
measure serum procalcitonin and C-reactive protein for the research study and store 
remaining specimen for potential future testing.   


(CCI) Committee on Clinical Investigations 
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Study Description – Part B 
CCI Form:  9-2015 
 
PI Revision Date:  2/24/2021  
 
Patients will be excluded if there is a clinical indication for new treatment with antibiotics, e.g. 
upper gastrointestinal hemorrhage or apparent infection, Standard of care treatment will 
never be delayed.  
Randomization: Each subject will be randomized to receive antibiotic treatment 
(ceftriaxone) or placebo (normal saline).  Randomization will be blinded to patients, study 
investigators, and study staff. Only the BIDMC Research pharmacist will know treatment 
assignment. Randomization will be stratified by the presence of either serum creatinine >= 
2.0 mg/dL and/or diuretic-refractory ascites.  
Study Intervention: The research pharmacy staff will provide antibiotic or placebo in 
the form of masked vials of intravenous solution. This will consist of either 1 gr ceftriaxone or 
an equal volume of normal saline (approximately 100 mL). This administration will begin as 
soon as possible after enrollment and will be repeated once daily. If a subject is prescribed 
an equivalent intravenous antibiotic during the hospitalization (i.e., ceftriaxone, 
piperacillin/tazobactam, or a carbapenem), the study-treatment (ceftriaxone/placebo) will be 
withheld on those days. If the clinically prescribed antibiotic is subsequently discontinued 
prior to discharge, the study-treatment/placebo may be resumed. Study treatment will be 
discontinued on study treatment day 7, or at the time of discharge or liver transplantation, if 
such events occur earlier than treatment day 7.  
Monitoring during Study Intervention:  Monitoring during study treatment will utilize 
routine vital sign monitoring and standard care labs conducted as indicated (typically daily) 
during the patient’s in patient stay. Standard care monitoring may also include radiographic 
or microbiology studies (e.g. culture) or special procedures such as therapeutic or diagnostic 
paracentesis at the discretion of the inpatient care team. No additional monitoring will be 
required per the study protocol. Standard care monitoring/labs that will be of interests include 
vital signs (e.g. blood pressure, mean arterial pressure, and oxygen saturation), CBC with 
WBC differential, bilirubin, INR, serum creatinine, sodium, albumin.  
 
Incidental Findings:  In the event that a clinically significant incidental finding is 
discovered during a research procedure, findings will be immediately reported to the 
attending on service for treatment or referral; results will be in OMR.  These would be also be 
available to the in-patients care team via OMR.  Examples of incidental findings include 
previously un-identified lung findings on chest x-ray, such as infection, pulmonary nodule, 
fracture, etc.   
 
Safety Monitoring: The PI is ultimately responsible for protecting the rights, safety, 
and welfare of subjects enrolled into the trial. Study intervention will last for 7 days during the 
patient’s inpatient stay for conditions related to the diagnosis of advanced cirrhosis/end stage 
liver disease.  Safety monitoring will be conducted daily during the intervention phase; post-
intervention procedures will continue daily during the patient’s admission and on day 30 post 
end of intervention.  The PI and/or a co-physician investigator will review all safety 
parameters including clinical safety laboratory assessments.  Clinical laboratory values that 
fall outside of the pre-specified safety ranges will be brought to the PIs attention the day the 
reports are final to assess clinical significance.   
 
Patients in the trial will be under the care of the in-patient liver service and these medical 
staff will be responsible for care of the patient throughout the admission.  
 
The study PI will review data of all non-serious adverse events after randomization of 
the first 5 subjects, and every additional 10 subjects thereafter until the study is complete. 


(CCI) Committee on Clinical Investigations 
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Study Description – Part B 
CCI Form:  9-2015 
 
PI Revision Date:  2/24/2021  
 
 
Monitoring for AE: Subjects will be monitored for the occurrence of adverse events 
during their participation in the study. Reporting procedures will comply with BIDMC IRB 
policies; US Federal Regulations (21CFR 312), and ICH Guideline E-6: Guidelines for Good 
Clinical Practice. 
 
Adverse events will be coded and graded according to the NIH/NCI Common 
Terminology Criteria for Adverse Events version 4.03 (June 2010).  All adverse events will be 
classified on seriousness (mild, moderate, serious), expectedness (expected, non-expected), 
and relatedness to trial (not related, possibly related, related).   
 
End of treatment: The study intervention will continue for 7 consecutive days (unless 
interrupted by equivalent antibiotic treatment for a new clinical indication). If the study 
intervention is interrupted the study intervention may be restarted following completion of the 
open label antibiotic treatment to complete the 7 days of study intervention.  
Follow-up Procedures:  Monitoring will continue until 30 days post-intervention.  
End of study: Subject data will be recorded for up to 30 days post-intervention. 
 
Data/Tissue Repository:  A data and bio-specimen repository will be created to 
permit future research on this topic. De-identified data for each subject will be stored in a 
restricted access, password-protected folder on the BIDMC network drive. This access will 
be limited to study personnel.  A master-code which links patient medical record number to 
the coded study subject ID will be stored in a separate location and available only to the PI 
and study personnel, as required for data entry. A blood specimen will also be collected from 
each subject upon enrollment for storage such that additional testing may be completed if 
preliminary results or subsequent knowledge suggest that another biomarker might have 
added prognostic significance. These specimens will be stored in a locked unit in the Liver 
Research Center (LMOB4) and coded with study ID only. Further testing on these specimens 
will not become part of the medical record.  
 
B. 
Statistical Considerations 
 
Sample Size Justification:  We estimate there will be a small prevalence of occult 
infection among patients who are believed to be eligible after initial screening is completed. 
Patients with identified infection at the time of enrollment will not be randomized and instead be 
treated as per standard of care at the discretion of the medical staff. We estimate there may be 
5-10 such patients who are thus enrolled but not randomized.    
 
We aim to randomize a total of 40 subjects, assigned to active intervention vs. placebo; 
hence as many as 50 may be screened / consented to determine eligibility. This is a pilot study 
intended to assess feasibility of patient identification, administration of required testing and 
enrollment processing, and the rate thereof. The magnitude of observed effect will permit 
sample size estimation for a larger, more definitive study which we hope to complete 
subsequently. It is unknown how many subjects will need to be screened to complete this 
planned enrollment. We will also obtain information on the dropout rate and/or rate of use of 
therapeutic antibiotics which may alter enrollment goals for a future study.  
 
Data Analysis:  As stated elsewhere, the proposed study is a pilot study, not intended to 
provide definitive results. However, there are multiple outcomes of interest that will be recorded 
in order to permit planning of a future study.  
 
The primary outcome is incident bacterial infection identified after randomization 


(CCI) Committee on Clinical Investigations 
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Study Description – Part B 
CCI Form:  9-2015 
 
PI Revision Date:  2/24/2021  
 
screening (as defined below). 
 
Secondary outcomes include: 
1. In-hospital mortality;  
2. 30-day mortality; 
3. Incident acute on chronic liver failure (ACLF) defined as two or more of:  
 Grade 3-4 hepatic encephalopathy, 
 Need for renal replacement therapy, 
 Need for mechanical ventilation, 
 Need for vasopressors, or mean arterial pressure (MAP) <60 mmHg, or decrement of 
>40 mmHg in systolic blood pressure after volume resuscitation. 
4. Change in calculated CLIF-C ACLF score; 
5. Length of stay (LOS) after randomization; 
6. Intensive Care Unit (ICU) transfer after randomization; 
7. C difficile infection (positive stool polymerase chain reaction (PCR) or toxin-assay in the 
setting of diarrhea); 
8. Increment in MELD-Na >= 3 points between randomization and discharge; 
9. Acute kidney injury (increase in creatinine >= 0.3 mg/dL in 48 hr or >50% from baseline 
(within previous 3 months) occurring after randomization; 
10. Variceal hemorrhage. 
 
Covariates recorded/measured 
 Procalcitonin at enrollment 
 C-reactive protein at enrollment 
 Other antibiotic use in-hospital (type and duration) 
 Fungal infections (by positive culture) or use of systemic anti-fungal medications. 
 
We will monitor daily for the incidence of the outcomes above via review of the 
medical record and discussions with the inpatient providers (when necessary). For any 
subject with a positive culture result, the site, organism, and antibiotic susceptibility will be 
recorded when available.  
 
Infection definitions  
 Bacteremia (positive blood culture not felt to be a skin flora contaminate)  
 Spontaneous bacterial peritonitis (ascites PMN count >250/ L or positive ascites culture 
in the setting of new abdominal pain, or unexplained leukocytosis, fever, hypotension, 
fever, acute kidney injury, or exacerbation of hepatic encephalopathy, i.e., increase in 
West Have grade)  
 Pneumonia: Pulmonary infiltrate on chest x-ray (CXR) or computed tomography (CT) in 
the presence of A) respiratory symptom(s) (cough, pleuritic pain, or dyspnea) or B) 
auscultation findings, abnormal body temperature (>38C or< 36C), or newly abnormal 
leukocyte count >10,000/microL or < 4,000/microL (if baseline leukocyte count > 
4,500/microL).    
 Skin or Soft Tissue Infection (SSTI): Superficial erythema, warmth, or fluctuance in the 


(CCI) Committee on Clinical Investigations 
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Study Description – Part B 
CCI Form:  9-2015 
 
PI Revision Date:  2/24/2021  
 
skin/soft tissues felt to be secondary to infection by the inpatient team, excluding mild 
superficial thrombophlebitis from IV catheter insertion 
 UTI: Urine leukocytes > 10/hpf, bacteruria, positive urine culture, urinary leukocyte 
esterase or nitrite in the presence of symptoms/signs of infection (dysuria, unexplained 
increased urinary frequency, fever, or leukocytosis) 
 Other infections as identified by the primary medical team 
 
 
For purposes of analysis, deidentified subject clinical data documenting the metrics 
above will be stored in a password protected file within the BIDMC network. Analysis will be 
conducted at BIDMC using R-studio software. There are no additional statistical consultants 
currently affiliated with this study. Descriptive statistics will include the incidence of the primary 
and secondary categorical outcomes in each arm with comparison via Chi-square test or 
Fisher’s exact test for rare events. As noted elsewhere, we do not anticipate this study will 
provide sufficient statistical power to demonstrate statistically significant differences between 
groups, but we will need to have an idea of the magnitude of effect prior to planning such a 
study and hope to obtain this information here.  
 
C. 
Subject Selection 
Potential subjects will be identified by attending hepatologists on the ward/consultation 
service during the course of clinical care and/or by study personnel via daily review of these 
patient lists in OMR. Patients meeting eligibility criteria below will be reviewed and 
approached to discuss the study, if appropriate.  
Inclusion Criteria:  
 Age >= 18  
 Cirrhosis, as defined by liver biopsy (completed as standard care) or a composite 
assessment of available results from imaging or elastography, prior records, and 
laboratory studies 
 MELD-Na >= 18 (Model for End Stage Liver Disease-Sodium, incorporating 
components of serum sodium, bilirubin, International Normalized Ratio (INR), and 
creatinine  
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) 
 Presence of ascites amenable to paracentesis without paracentesis performed as 
SOC for exclusion of infection 
 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)  
 History of recurrent C.difficile infection within the past year (>2 episodes) or requiring 
prior fecal microbiota transplant (FMT) 
 Enrollment in the study protocol during a previous admission 
 
 
There are no specific limitations regarding gender or racial distribution of the planned 
population studied and as such, our intended sample will reflect a subset of these patients 


(CCI) Committee on Clinical Investigations 
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Study Description – Part B 
CCI Form:  9-2015 
 
PI Revision Date:  2/24/2021  
 
without selection based on either parameter. The only exception to this is pregnant women will 
be excluded due to theoretical risk of adverse effect of ceftriaxone exposure (Pregnancy 
category B). Please note that is exceptionally rare to encounter a pregnant patient with this 
degree of chronic liver illness. 
 
There are no specific requirements for contraception during this short study conducted with 
patients admitted to the hospital.  
 
B4. 
POSSIBLE BENEFITS 
Subjects may receive benefit via reduction in the risk or severity of infection during the 
admission. There may also be reduction in length of hospital stay or other complications such 
as indirect benefits such as rate of ICU transfer, variceal hemorrhage, or death. These will be 
identified in comparison to similar outcomes among subjects receiving placebo, noting, as 
above, that this is a pilot study, not intended to confirm such a benefit.  
The benefit to society would be validating the design of a larger trial which could confirm 
such benefits and thus improve medical care and metrics important to patients, such as length 
of stay and mortality.  
 
B5. 
POSSIBLE RISKS AND ANALYSIS OF RISK/BENEFIT RATIO 
 
Risks of participation in the study include reaction to the antibiotic used in the trial: 
Ceftriaxone is commonly used to treat patients with end stage liver disease, and subjects may 
be prescribed ceftriaxone as routine care even if they do not participate in this trial.   
 
Regardless of which treatment the subject is assigned, the study medication will be 
administered intravenously (IV), peripherally or via central venous catheter if one is already in 
place for routine care.    
 
 
Side effects rarely observed in patients receiving any type of fluid intravenously 
include fever, infection at the site of IV insertion, blood clot in the vein, or inflammation of the 
vein extending from the site of injection, IV fluid leakage into the tissue around the IV 
insertion, and fluid overload.  
 
Subjects randomized to receive ceftriaxone, may experience side effects that have 
been observed in prior clinical trials.     
 The most common side effects (>10%) observed in clinical trials of ceftriaxone include 
skin tightness, thickening of the skin, and a warm sensation around the site of the 
injection when ceftriaxone was administered as an intermuscular injection.   
 Less common side effects ( <10%) included pain and tenderness at the injection site 
when the drug is given as an intermuscular injection; skin rash, diarrhea, eosinophilia 
(excess of inflammatory/allergic blood cells), thrombocytopenia (excess of 
platelets/blood clotting-cells), leukopenia (low level of white/infection-fighting blood 
cells), increased serum transaminases (liver blood tests which may suggest liver 
injury) and increased blood urea nitrogen (a marker of kidney function).  
 Allergic reaction to the study drug which can vary in severity from asymptomatic rash, to 
pruritic (itchy) rash, to hives, to anaphylaxis (a life threatening allergic reaction). 
 Indirect adverse effect of the study drug: development of antibiotic resistance, 


(CCI) Committee on Clinical Investigations 
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Study Description – Part B 
CCI Form:  9-2015 
 
PI Revision Date:  2/24/2021  
 
opportunistic infection- C difficile colitis or fungal infection. Diagnostic uncertainty related 
to treatment of subsequent infections. 
 
Subjects randomized to receive placebo, will receive approximately 100 mL (less than 
7 tablespoons) of normal saline. There are no additional side effects expected beyond those 
listed above. 
 
Blood draw and receiving medication intravenously:  The risks and discomforts of 
drawing blood from a vein include the possibility of pain or bruising at the site of the blood 
draw, occasional feeling of lightheadedness, and rarely, infection or blood clotting at the site 
of the blood draw. 
 
Some participants may need one or all of the following tests for the study:  
 
Chest X-Ray/Radiation Risk:   
 
Some patients may get a chest x-ray to rule out infection at screening if one has not 
been completed as standard care. Radiation exposure from a single chest x-ray will deliver 
approximately 0.2 milliSieverts, a measure of radiation exposure. For comparison, the 
average person in the United States receives a radiation exposure of 3.2 milliSieverts per 
year from natural background and exposures we encounter in our everyday life. One possible 
effect from this additional radiation exposure is an increase in the risk of cancer. The 
estimated increase in the cancer risk due to this radiation exposure is 0.002%. 
 
 
Other Tests, Imaging Studies, and Procedures: Based on the severity of your 
condition or if your disease worsens, you may be asked to undergo other diagnostic tests, 
imaging studies (e.g., ultrasound), and procedures as a standard of care for your condition.  
There may be risks associated with these tests, imaging studies, and procedures.  Your 
doctor will explain the risks associated with each test/study/procedure and you may be asked 
to sign a separate informed consent form depending on the test/study/procedure being 
performed. 
 
Loss of confidentiality: There is the potential for loss of confidentiality by 
participating in this study.  Every effort will be made to protect the confidentiality of your 
identifiable information.   
 
We feel that the potential benefit to this patient population of this type of treatment 
outweighs these risks. We have attempted to minimize risk by exclusion of subjects deemed to 
be at greater risk of adverse reaction (e.g. history of allergy to cephalosporins or recurrent 
clostridium difficile infection), permitted non-study clinical teams to provide treatment without 
limitation, and minimized the number of subjects exposed to the intervention. The potential 
benefit to future patients could include reduced admission length or mortality rate.  
 


(CCI) Committee on Clinical Investigations 
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Study Description – Part B 
CCI Form:  9-2015 
 
PI Revision Date:  2/24/2021  
 
B6. 
RECRUITMENT AND CONSENT PROCEDURES 
 
Recruitment: Study participants will be identified from among the ranks of patients 
admitted to the BIDMC (Emergency Department and/or Liver Service) with end stage liver 
disease and advanced cirrhosis. 
 
The PI and physician co-Investigators will identify patients admitted to their Service 
(Liver / Transplant Services) who meet preliminary eligibility criteria.  Thereafter, a physician 
investigator will meet with the potential participant to introduce the study.  If the patient does 
not have capacity to consent, the Investigator will identify the patient’s Health Care Proxy / 
Legally Authorized Representative (LAR) to introduce the study.   
           Due to the COVID-19 global pandemic and hospital wide visitor restriction policies, 
informed consent will be conducted remotely via telephone with the patient’s LAR when 
necessary.  
 
Once the potential participant/LAR indicates willingness to consider enrollment, the 
physician investigator will explain the study in clear, easy-to-understand language; review study 
purpose and goals, study treatment, procedures (including randomization), burdens and 
benefits, and schedules.  Any questions from a potential participant/LAR regarding the study will 
be answered by the study investigator. 
 
Consent: Consent procedures will be completed for patients in a private setting beyond 
the ear shot of others. The physician investigator will review all study procedures, and risks 
and benefits will be discussed.  The patient/LAR will be given ample time to ask questions and 
all questions will be answered. If the patient/LAR wishes to discuss participation with others, 
arrangements will be made to facilitate/expedite these discussions as time from subject 
identification to treatment is of importance.     
 
Patients/LAR willing to consent to participation will be required to sign and date the 
BIDMC CCI approved consent; the Investigator completing consent procedures will also sign 
and date the consent document. The original consent will be maintained in the subject’s 
research record, a copy will be placed in the subject’s medical record, and a copy of the signed 
consent will be given to the subject.  
           When conducting consent remotely, a consent document will be emailed to the patient’s 
LAR. Once the investigator and LAR both have a hard copy of the consent document in front of 
them, the consent document will be reviewed according to the same standards as outline 
above. If the LAR is willing to consent to study participation, they will sign the consent 
document and email or fax return a picture of the consent document signature page to study 
staff. The signature page signed by the LAR will be filed in the patient’s research record 
alongside the consent document signed by the Investigator. A copy of both signed documents 
will be emailed to the LAR for their records.  
 
If informed consent is obtained from a LAR, capacity for consent will be documented in 
the medical record. Once the subject’s condition improves such that s/he regains capacity, 
informed consent for continued study participation will be obtained from the subject at that 
time. A separate ICF will be used to complete this consent. 
Subject Protection:  We do not 
believe potential participants are vulnerable to coercion or undue influence. Patients admitted 
to the hospital with advanced chronic liver disease frequently present with hepatic 
encephalopathy.  To exclude these patients would exclude a substantial group for whom the 
study is specifically intended to help.  When investigators encounter a patient who does not 
have capacity to consent, the LAR will be identified and approached to obtain consent on 


(CCI) Committee on Clinical Investigations 
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Study Description – Part B 
CCI Form:  9-2015 
 
PI Revision Date:  2/24/2021  
 
behalf of the potential subject. At such time as the patient regains capacity, the investigator will 
complete consent procedures directly with the subject. 
 
We will not enroll prisoners into the study.  
 
B7. 
STUDY LOCATION 
 
Privacy: Consent procedures will be completed in a private hospital setting, beyond 
earshot of others by study investigators during the patient’s hospital admission, e.g. private 
exam room, in-patient hospital room, etc.   
 
Study procedures will be completed in various hospital settings, outpatient clinic or on 
the telephone. Patient privacy will be maintained in accordance with hospital policy and 
procedures. Medical record reviews will be completed by study staff at workstations in 
BIDMC research and clinical staff offices. Information collected will be limited to the minimum 
amount of data necessary to accomplish the research purposes.  
 
All investigators and study staff are trained in HIPAA guidelines and requirements as 
well as Human Subjects Protections best practices. Only the investigators and study staff 
have access to data that identifies subjects by name. Subjects are assigned a unique study 
identifier and all subject records will be void of subject identifiers.   
 
Only investigators listed will be able to connect individual subject information with 
research data. Data will be kept on a password protected database on a firewall-protected, 
BIDMC password protected computer in a restricted access location. 
 
Physical Setting: Study investigators will interact with potential subjects during a 
hospitalization and following outpatient clinic visits in the Liver Center or Transplant Center. 
Subjects may be contact by phone in the event they do not return to the Center for a follow 
up visits prior to Day 30 post study treatment.  
 


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Study Description – Part B 
CCI Form:  9-2015 
 
PI Revision Date:  2/24/2021  
 
B8. 
DATA SECURITY 
 
Study staff is trained in human subject protections regulation including hospital 
mandated CITI and HIPAA standards.  Access to clinical medical records used for the trial is 
strictly limited in accordance with hospital policies.  Data abstracted from medical records will 
be managed in compliance with clinical research best practices; both hard copy and 
electronic data collected for the investigation will be stored in restricted access files in the 
Division’s Clinical Research Offices and in electronic files and folders behind hospital 
firewalls. Data included in analytic files will be de-identified and the key linking data to patient 
identity will be maintained by the investigators in a separated restricted access location. 
 
B9 
Multi-Site Studies 
 
Is the BIDMC the coordinating site?       
 Yes    
 No Not applicable 
Is the BIDMC PI the lead investigator of the multi-site study?     
 Yes    
 No Not applicable 
 
B10 
Dissemination of Research Results 
 
In this pilot study to determine feasibility of case finding, rate of enrollment, data 
capture, and specimen collection and processing 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. There will be no subject specific outcomes to 
present to participants. 
 
The results of this study may be published and/or presented at scientific meetings in 
accordance with customary academic, editorial, and ethical practices and requirements. 
 

ICF_001.pdf: 
NCT Number:  
NCT04218695 
Official Title: 
A Pilot Study of the Effect of Prophylactic Antibiotics on Hospitalized 
Patients With Advanced Cirrhosis 
Document Type: 
Informed Consent 
Document Date: 
1/26/2021 


[CCI] Committee on Clinical Investigations 
 
Page 1 of 18 
 
 
Informed Consent – Part D 
CCI Form: 12-2018 
PI Revision Date: 01/26/2021 
 
**FOR CCI USE ONLY** 
Approved by the Beth Israel Deaconess Medical Center  
Committee on Clinical Investigations:  
 
Consent Approval Date:   01/10/2022 
 
 
 
Protocol Number:  
2020P000050 
 
   
 
 
 
 
 
INFORMED CONSENT FORM TO TAKE PART IN A RESEARCH STUDY 
 
SUBJECT’S NAME:        
TITLE OF RESEARCH PROTOCOL: A pilot study of the effect of prophylactic antibiotics on hospitalized patients 
with advanced cirrhosis          
PRINCIPAL INVESTIGATOR:       Zachary Fricker, MD 
PROTOCOL NUMBER:  2020P000050 
 
KEY INFORMATION ______ 
 
The following is a short summary of this study to help you decide whether or not to be a part of this 
study. More detailed information is listed later on in this form.  
Why am I being invited to take part in a research study?  
We invite you to take part in a research study because you have advanced cirrhosis of the liver and 
are admitted to the hospital. Liver cirrhosis is extensive scarring of the liver that impairs liver 
function. 
What should I know about a research study?  
• 
Someone will explain this research study to you. 
• 
Whether or not you take part is up to you. 
• 
Your participation is completely voluntary. 
• 
You can choose not to take part. 
• 
You can agree to take part and later change your mind. 
• 
Your decision will not be held against you.   
 Your refusal to participate will not result in any consequences or any loss of benefits that you 
are otherwise entitled to receive. 
 You can ask all the questions you want before you decide. 
 If you choose not to take part, or if you leave the study, your decision will in no way harm your 
relationship with any member of the research team or any other individuals at Beth Israel 
Deaconess Medical Center. 
 
Why is this research being done?  
 
COMMITTEE ON CLINICAL INVESTIGATIONS 
APPROVAL EXPIRATION DATE 
 
01/09/2023


[CCI] Committee on Clinical Investigations 
Page 2 of 18 
 
SUBJECT'S NAME: 
TITLE OF RESEARCH PROTOCOL: A pilot study of the effect of 
prophylactic antibiotics on hospitalized patients with advanced 
cirrhosis   
PRINCIPAL INVESTIGATOR'S NAME: ZACHARY FRICKER, MD 
PROTOCOL #:  2020P000050 
 
 
Informed Consent – Part D 
CCI Form: 12-2018 
PI Revision Date:  1/26/2021 
 
 
 
Patients with advanced cirrhosis are at increased risk for harmful bacterial infections. Preventing 
infections might be possible with antibiotics during a hospital admission. We would like to know if this 
is true and compare the risks of antibiotic use to the benefits. We would also like to determine if any 
patient characteristics or blood tests can be used to identify patients at greater risk for infection. We 
would like to answer these questions by studying the effect of antibiotics among this group of 
patients. We are conducting this preliminary study to determine if a larger, more definitive study is 
possible.   
How long will the research last and what will I need to do?  
We expect that you will be in this research study for 7-days (during which you may receive 
antibiotics) and at no longer than 30 days (we may contact you via phone to determine your status 
after hospital discharge).   
We will collect and store a blood sample (approximately 1 tablespoon) for potential future testing, 
based on the study results, which are unknown at this time. We will store this sample indefinitely.  
You will be asked to undergo testing (blood and urine testing and a chest x-ray) to see if you have an 
infection, if not already done. You will provide blood samples for two extra blood tests for research, 
and you will be randomly assigned to receive an antibiotic or placebo (inactive fluid).  
More detailed information about the study procedures can be found under “DESCRIPTION OF 
STUDY DETAILS”. 
 
 
Is there any way being in this study could be harmful to me?  
The most common risks of participating in this study include injury that might occur during testing to 
determine if you have an infection, if required, (such as bleeding from a needle puncture site, 
causing an infection), or side effect from the study medication (antibiotic), such as allergic reaction, 
diarrheal infection, or the development of antibiotic –resistant infection.  
More detailed information about the risks can be found under “RISKS AND DISCOMFORTS”.   
Will being in this study help me in any way?  
We cannot promise any benefits to you or others from your taking part in this research. However, 
possible benefits to others include improvements in medical care for future hospitalized patients with 
cirrhosis which may reduce the risk of infection or the unnecessary use of antibiotics.   
What happens if I do not want to be in this research? 
Participation in research is completely voluntary. You can decide to participate or not to participate. 
Your alternative to participating in this research study is to not participate. 
 
COMMITTEE ON CLINICAL INVESTIGATIONS 
APPROVAL EXPIRATION DATE 
 
01/09/2023


[CCI] Committee on Clinical Investigations 
Page 3 of 18 
 
SUBJECT'S NAME: 
TITLE OF RESEARCH PROTOCOL: A pilot study of the effect of 
prophylactic antibiotics on hospitalized patients with advanced 
cirrhosis   
PRINCIPAL INVESTIGATOR'S NAME: ZACHARY FRICKER, MD 
PROTOCOL #:  2020P000050 
 
 
Informed Consent – Part D 
CCI Form: 12-2018 
PI Revision Date:  1/26/2021 
 
 
 
 
DETAILED INFORMATION SECTION__________________________________________________ 
Please read this consent form carefully and ask the investigators or study staff to explain any words or 
information that you do not clearly understand.  Once you read this consent form and understand what 
your participation in this study will involve, you will be asked to sign this form if you wish to take part.  
You will be given a signed copy of the form to keep for your records. 
 
DISCLOSURE OF SPECIAL INTERESTS OF BIDMC AND INVESTIGATORS 
This study is being conducted by Zachary Fricker, MD and is funded by the American Association for 
the Study of Liver Diseases Foundation. The funding agency in this study (American Association for 
the Study of Liver Diseases Foundation) is paying Beth Israel Deaconess Medical Center (BIDMC) to 
perform this research.  Neither BIDMC nor Dr. Fricker has any additional interests in this research 
project.  
 
WHOM TO CONTACT IF YOU HAVE QUESTIONS OR PROBLEMS 
If you have any questions, concerns or complaints about this research or experience any problems, 
you should contact the Principal Investigator Zachery Fricker at [617] 632-1070.  
 
PURPOSE 
We are interested in learning the risks and benefits of providing antibiotics to patients with advanced 
cirrhosis who are hospitalized. This pilot study is being conducted to determine if a larger, future study 
would be possible. These future studies would assess whether antibiotic medication can be used to 
reduce infections that develop in hospitalized patients. We would also like to see whether antibiotic 
medication affects outcomes, such as length of hospital stay, worsening of laboratory tests, or death. 
We would also like to assess if patients most likely to benefit from antibiotic treatment can be identified 
using blood tests.  
 
The treatment proposed is a new use of a commonly used antibiotic medication (Ceftriaxone). It is 
unknown if using this medication in patients without known infection will be beneficial. Ceftriaxone is an 
FDA approved antibiotic for the treatment or prevention of infections that are proven or strongly 
suspected to be caused by bacteria. It has not been specifically approved by the FDA for the 
prevention of infection in your condition, however, many doctors in the community commonly 
prescribe ceftriaxone to treat bacterial infections or prevent bacterial infections in patients with 
cirrhosis and bleeding from the esophagus, stomach, or intestine. 
 
STUDY PARTICIPANTS 
You have been asked to be in the study because you have cirrhosis and are admitted to the hospital.  
 
 
COMMITTEE ON CLINICAL INVESTIGATIONS 
APPROVAL EXPIRATION DATE 
 
01/09/2023


[CCI] Committee on Clinical Investigations 
Page 4 of 18 
 
SUBJECT'S NAME: 
TITLE OF RESEARCH PROTOCOL: A pilot study of the effect of 
prophylactic antibiotics on hospitalized patients with advanced 
cirrhosis   
PRINCIPAL INVESTIGATOR'S NAME: ZACHARY FRICKER, MD 
PROTOCOL #:  2020P000050 
 
 
Informed Consent – Part D 
CCI Form: 12-2018 
PI Revision Date:  1/26/2021 
 
 
 
Approximately 50 people will take part in this study at Beth Israel Deaconess Medical Center.  BIDMC 
is the only site to conduct this study. 
 
DESCRIPTION OF STUDY DETAILS 
If you agree to be in this study, you may take the study drug (or placebo) for as long as one week and 
your medical record may be reviewed by study staff throughout your hospital admission and then for 
up to one month after enrollment.  
 
After you sign the consent form, the following things will happen: 
 
1. Screening Procedures:  Screening procedures are tests and procedures that are required to 
determine if you are eligible to take part in the research study.  Most all of these procedures 
will already be completed for your standard care and we will obtain the results from your 
medical record.  If not, they may be required for this research study:  
 Urine culture (you will be asked to urinate into a collection container, this sample will be 
tested for bacteria; requires about 1 tablespoon of urine), and  
 Blood cultures (you will have blood drawn from a vein to test for bacteria; requires about 1 
tablespoon of blood).  
 Chest x-ray (you would be asked to stand still and briefly hold your breath while a 
radiology technician performs an x-ray),  
 Study blood tests: Approximately 2 tablespoons of blood will be drawn to complete study 
blood test including serum procalcitonin which helps to diagnosis types of infections, and 
C-reactive protein which helps to identify presence of inflammation and to monitor 
response to treatment for an inflammatory disorder; and a specimen will be stored for 
future research.  
 Clinical lab tests results from routine care: including but not limited to complete blood 
count with differential (a measurement of the types of blood cells and their relative 
proportion in the blood which can indicate infection may be present), blood clotting tests 
(measurement of the bloods ability to clot), serum creatinine (an estimate of kidney 
function), bilirubin (an estimate of liver function), sodium (a normal chemical in the blood), 
albumin (a normal protein in the blood), and pregnancy test results for women who can 
become pregnant.   
 
2. Randomization Procedures:  If there is no sign of infection based on the screening tests 
above, you will be randomly assigned to receive one of two study treatments. 
 
It is not clear at this time which of the treatments in this study would be better for you.  For 
this reason, the treatment plan offered to you will be picked by chance [like the flip of a coin].  
 
COMMITTEE ON CLINICAL INVESTIGATIONS 
APPROVAL EXPIRATION DATE 
 
01/09/2023


[CCI] Committee on Clinical Investigations 
Page 5 of 18 
 
SUBJECT'S NAME: 
TITLE OF RESEARCH PROTOCOL: A pilot study of the effect of 
prophylactic antibiotics on hospitalized patients with advanced 
cirrhosis   
PRINCIPAL INVESTIGATOR'S NAME: ZACHARY FRICKER, MD 
PROTOCOL #:  2020P000050 
 
 
Informed Consent – Part D 
CCI Form: 12-2018 
PI Revision Date:  1/26/2021 
 
 
 
You will not be able to choose which treatment you receive.  The chances of receiving either 
of the treatments are approximately equal. After the randomization, you will be assigned to 
one of the following groups: 
A) Antibiotic (ceftriaxone)  
B) Placebo (normal saline fluid) 
Placebo:  Depending upon the group to which you are assigned, you may receive a placebo 
instead of the antibiotic ceftriaxone.  A placebo is an inactive intravenous fluid (salt and 
water) that looks like the study drug, but a placebo contains no active medication.  Placebos 
are used to help determine if the results of the study are truly from the study drug.  You will 
not know whether you will be receiving the study drug or the placebo.  However, this 
information can be learned in case of an emergency. 
 
Double-blind study:  Neither you nor your physician will know which intervention you are 
receiving.  However this information can be learned in case of an emergency. 
 
3. Research Procedures:  If you qualify to take part in this research study, you will undergo 
these research procedures:  You will randomly be assigned to receive either the study 
antibiotic (ceftriaxone) or the placebo once daily for up to 7 days. The study drug will be 
administered to you intravenously (IV), through a tube inserted into your arm or through a 
central venous line if you already have one placed.  We will record laboratory values and vital 
signs (e.g. heart rate, blood pressure) in a database for later review. If your physicians feel 
that you require antibiotics for any period of time, you may receive these as you normally 
would. We may or may not administer the study medication during this time, depending on the 
type of antibiotic your doctors feel you require.  
 
4. Monitoring/Follow-Up Procedures.  Procedures performed to evaluate the effectiveness and 
safety of the research procedures are called “monitoring” or “follow-up” procedures.  For this 
research study, the monitoring/follow-up procedures are listed in the table below. Most of 
these procedures are completed as a part of your standard care. We will get the results of 
those procedures and tests from your medical records.  If no medical records are available at 
30-days after you leave the hospital, a research coordinator from our team will call you to 
follow-up with you directly to see how you have been feeling since your discharge.  
 
Study Visit / Timeline 
Screening 
Day 1 
Days 1-7 
Day 30 
Blood and urine collection   
X 
X 
X 
 
 
Blood culture to rule out infection  
X 
X 
X 
 
 
COMMITTEE ON CLINICAL INVESTIGATIONS 
APPROVAL EXPIRATION DATE 
 
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[CCI] Committee on Clinical Investigations 
Page 6 of 18 
 
SUBJECT'S NAME: 
TITLE OF RESEARCH PROTOCOL: A pilot study of the effect of 
prophylactic antibiotics on hospitalized patients with advanced 
cirrhosis   
PRINCIPAL INVESTIGATOR'S NAME: ZACHARY FRICKER, MD 
PROTOCOL #:  2020P000050 
 
 
Informed Consent – Part D 
CCI Form: 12-2018 
PI Revision Date:  1/26/2021 
 
 
 
 
Study blood tests 
X 
X 
 
 
 
Clinical lab tests  
X 
X 
X 
X 
 
Urine culture and urinalysis to rule out 
infection  
X 
X 
 
 
 
Pregnancy test for women who are able to 
become pregnant  
X 
 
 
 
Chest x-ray to rule out infection  
X 
X 
X 
 
 
 
 
 
 
Study treatment   
 
 
X 
 
Possible phone call 
 
 
 
X 
Review of your medical record 
X 
X 
X 
X 
 
Individual Research Results 
Your study doctor will disclose any clinically relevant research results to you, including findings from 
the chest x-ray, and/or blood and urine cultures, if performed. The results of the study tests will be in 
your medical record and the doctors treating you will have access to all of these results.   
Most tests done on samples in research studies are only for research and have no clear meaning for 
health care. The research testing done in this study is just a stepping stone to learning more about 
liver cirrhosis.     
 
While you should not expect to receive any results from the testing completed only for research, if 
we find that research results from your sample are of high medical importance, we may attempt to 
contact your medical provider to discuss the results. In some situations, follow up testing might be 
needed in a Clinical Laboratory Improvement Amendments (CLIA) certified clinical lab. You and your 
medical insurer may be responsible for the costs of these tests and any follow up care, including 
deductibles and co-payments. It is possible that you will never be contacted with individual research 
findings. This does not mean that you don’t have or won’t develop an important health problem.  
 
Information and Biological Samples 
Your information and biological samples will be used and shared with the researchers involved in 
this study to conduct the research.  The consent form provides information on who will have access 
to identifiable information and identifiable biological samples during the study.  We also want you to 
know that your information or biological samples may be stripped of any identifiers (for example your 
name, medical record number or date of birth) and used for future research studies or distributed to 
 
COMMITTEE ON CLINICAL INVESTIGATIONS 
APPROVAL EXPIRATION DATE 
 
01/09/2023


[CCI] Committee on Clinical Investigations 
Page 7 of 18 
 
SUBJECT'S NAME: 
TITLE OF RESEARCH PROTOCOL: A pilot study of the effect of 
prophylactic antibiotics on hospitalized patients with advanced 
cirrhosis   
PRINCIPAL INVESTIGATOR'S NAME: ZACHARY FRICKER, MD 
PROTOCOL #:  2020P000050 
 
 
Informed Consent – Part D 
CCI Form: 12-2018 
PI Revision Date:  1/26/2021 
 
 
 
another researcher for future research studies without additional informed consent.  BIDMC 
researchers or other third party researchers may use your information and samples in other scientific 
research, product testing or commercial development. It is unknown whether a product will ultimately be 
developed from the research described in this consent form or from any such work that may be 
performed by BIDMC or other third parties receiving your information or biological samples.  In signing 
this consent form, you are acknowledging and voluntarily consenting to the possibility that your 
information and biological samples may be used for commercial purposes.   For example, your samples 
and information may be used to develop a new product or medical test to be sold. BIDMC and other 
researchers may benefit if this happens. There are no plans to pay you if your samples and information 
are used for this purpose. 
 
If your identifiers are removed, we will not be able to destroy or remove your information or biological 
samples from distributed information or samples.  As part of this research program and as further 
explained in this form, samples of your tissue and/or information about your medical history may be 
provided to other researchers and/or outside collaborators.  
 
Storing of Identifiable Information and Samples for Future Use 
At the completion of this research, we would like to store any remaining sample(s) and information 
collected from or about you for this research for possible future use.  Your sample will be stored in a 
manner that allows association with your identifiers, such as your name or medical record number.  
The remaining samples and information may be stored indefinitely and may be used for future 
research of cirrhosis or infections. The research staff will have a list to know which sample is linked 
to which participant and this list will be kept confidential in a secure location. If the research 
investigator distributes your samples to other researchers or institutions, they will be labeled with a 
research code without identifiers so that you cannot be identified by the other researchers or 
institutions.  
 
If you have questions about storing samples or information, or would like to request that samples or 
information be removed from storage, please let us know.  It is not always possible to remove 
samples or information from storage or to retrieve samples or information that have/has already 
been sent to other investigators. 
 
I agree to allow my samples and information to be stored and used for future research as described 
above: (please check and initial one to indicate your choice)  
 
_____   YES  
______   NO 
 
 
RISKS AND DISCOMFORTS 
 
COMMITTEE ON CLINICAL INVESTIGATIONS 
APPROVAL EXPIRATION DATE 
 
01/09/2023


[CCI] Committee on Clinical Investigations 
Page 8 of 18 
 
SUBJECT'S NAME: 
TITLE OF RESEARCH PROTOCOL: A pilot study of the effect of 
prophylactic antibiotics on hospitalized patients with advanced 
cirrhosis   
PRINCIPAL INVESTIGATOR'S NAME: ZACHARY FRICKER, MD 
PROTOCOL #:  2020P000050 
 
 
Informed Consent – Part D 
CCI Form: 12-2018 
PI Revision Date:  1/26/2021 
 
 
 
As a result of your participation in this study, you are at risk for side effects listed in this section.  You 
should discuss these with the investigator and with your regular doctor if you choose. 
 
Regardless of which treatment you are assigned, the study medication will be administered to you 
intravenously (IV) through a sterile tube placed in a vein in your arm or in a central venous catheter if 
you already have one placed.  The medication you receive will be in an IV medication bag that is 
labeled in a manner that does not reveal the contents. Side effects rarely observed in patients 
receiving any type of fluid intravenously include fever, infection at the site of IV insertion, blood clot in 
the vein, or inflammation of the vein extending from the site of injection, IV fluid leakage into the 
tissue around the IV insertion, and fluid overload.  
If you are randomized to receive the antibiotic Ceftriaxone, you may experience side effects that 
have been observed in prior clinical trials.     
 The most common side effects (>10%) observed in clinical trials of ceftriaxone include skin 
tightness, thickening of the skin, and a warm sensation around the site of the injection when 
ceftriaxone was administered as an intramuscular injection (injection into a muscle).   
 Less common side effects ( <10%) included pain and tenderness at the injection site when 
the drug is given as an intramuscular injection; skin rash, diarrhea, eosinophilia (increase in 
the number of the white blood cells called eosinophils), thrombocytopenia (decrease in blood 
platelets; the blood cells that help blood clot), leucopenia (low level of white blood cells in the 
blood, which can interfere with the ability to fight infection), Increased in the liver enzyme, 
serum transaminases (suggesting liver injury) and allergic reactions to the drug and increased 
blood urea nitrogen (a marker of kidney function). Indirect adverse effects of ceftriaxone 
include development of antibiotic resistance, opportunistic infections which are infections that 
occur when a person is ill especially when the immune system is weak. Opportunistic 
infections may be caused by common bacteria (such as the bacteria called C-difficile) and 
fungi and often cause inflammation of the colon (colitis) and pain such as stomach pain, 
cramping and diarrhea; diagnostic uncertainty related to treatment of subsequent infections. 
If you are randomized to receive placebo, you will receive approximately 100 mL (less than 7 
tablespoons) of normal saline (salt water). There are no additional side effects expected beyond 
those listed above. 
 
Blood draw and receiving medication intravenously:  The risks and discomforts of drawing blood 
from a vein include the possibility of pain or bruising at the site of the blood draw, occasional feeling 
of lightheadedness, and rarely, infection or blood clotting at the site of the blood draw. 
 
If not already completed for standard care and treatment, you may need one or all of the following 
tests for the study:  
 
COMMITTEE ON CLINICAL INVESTIGATIONS 
APPROVAL EXPIRATION DATE 
 
01/09/2023


[CCI] Committee on Clinical Investigations 
Page 9 of 18 
 
SUBJECT'S NAME: 
TITLE OF RESEARCH PROTOCOL: A pilot study of the effect of 
prophylactic antibiotics on hospitalized patients with advanced 
cirrhosis   
PRINCIPAL INVESTIGATOR'S NAME: ZACHARY FRICKER, MD 
PROTOCOL #:  2020P000050 
 
 
Informed Consent – Part D 
CCI Form: 12-2018 
PI Revision Date:  1/26/2021 
 
 
 
 
Chest X-Ray/Radiation Risk:   
Some patients may get a chest x-ray to rule out infection at screening if one has not been completed 
as standard care. In this instance you would receive radiation exposure that is not necessary for your 
medical care.  This exposure would be in addition to any exposure you receive as part of your 
routine medical care.  
 
Radiation exposure from a single chest x-ray will deliver approximately 0.2 milliSieverts, a measure 
of radiation exposure. For comparison, the average person in the United States receives a radiation 
exposure of 3.2 milliSieverts per year from natural background and exposures we encounter in our 
everyday life. One possible effect from this additional radiation exposure is an increase in the risk of 
cancer. The estimated increase in the cancer risk due to this radiation exposure is 0.002%. 
 
If you are pregnant, you will not be able to participate in this research study. It is best to avoid 
radiation exposure to unborn children because they are more sensitive to radiation than adults. 
 
Loss of confidentiality  
There is the potential for loss of confidentiality by participating in this study.  Every effort will be 
made to protect the confidentiality of your identifiable information.   
 
CONFIDENTIALITY 
Information learned about you during this research program will be maintained confidentially by the 
research staff as described in this form.  
 
Information learned from your participation in this study and from your medical record may be 
reviewed and photocopied by the Food and Drug Administration (FDA) and/or other federal and state 
regulatory agencies, the Committee on Clinical Investigations, the Human Subjects Protection Office 
and others involved in research administration of the Beth Israel Deaconess Medical Center.  
Information resulting from this study and from your medical record may be used for research 
purposes and may be published; however, you will not be identified by name in such publications. 
 
MEDICAL RECORD 
A copy of this consent form and information collected during this research may become part of your 
medical record, if the information is relevant to the care you receive at Beth Israel Deaconess 
Medical Center.  Medical records are considered permanent records; therefore, information cannot 
be deleted from the record.  Medical records are available to health care professionals at Beth Israel 
Deaconess Medical Center and may be reviewed by staff when carrying out their responsibilities, as 
well as by external parties such as health care insurers and others in certain circumstances.   
 
COMMITTEE ON CLINICAL INVESTIGATIONS 
APPROVAL EXPIRATION DATE 
 
01/09/2023


[CCI] Committee on Clinical Investigations 
Page 10 of 18 
 
SUBJECT'S NAME: 
TITLE OF RESEARCH PROTOCOL: A pilot study of the effect of 
prophylactic antibiotics on hospitalized patients with advanced 
cirrhosis   
PRINCIPAL INVESTIGATOR'S NAME: ZACHARY FRICKER, MD 
PROTOCOL #:  2020P000050 
 
 
Informed Consent – Part D 
CCI Form: 12-2018 
PI Revision Date:  1/26/2021 
 
 
 
 
POSSIBLE BENEFITS 
It is not possible to predict whether you will benefit directly from participation in this study.  However, 
your participation may help others in the future as a result of knowledge gained from the research. 
 
OTHER AVAILABLE OPTIONS 
Taking part in this study is voluntary. Instead of being in this study, you have the following options: 
not participating and receiving routine medical care as you otherwise would.  
 
It is important to note that it is possible to get ceftriaxone even if you do not take part in the study. 
Ceftriaxone has not been approved by the FDA for the prevention of infection in your condition, 
however, many doctors in the community commonly prescribe ceftriaxone to treat bacterial infections 
or prevent bacterial infections in patients with cirrhosis and bleeding from the esophagus, stomach, 
or intestine. Please be aware that not all doctors may agree to prescribe this drug for you, and that 
not all health insurance companies will pay for the drug when it is prescribed for prevention of 
infection.  
 
This research study is not meant to diagnose or treat medical problems. Participation in this research 
study does not take the place of routine physical examinations or visits to your regular doctor. 
 
We recommend that you discuss these and other options with the investigator and your regular 
doctor so that you can make a well-informed decision about participating in this study. 
 
IF YOU DECIDE NOT TO TAKE PART IN THE STUDY 
Participation in this study is voluntary.  You have the right to decide not to take part in this study.  If 
you choose to participate, you have the right to leave the study at any time. Your decision to not 
participate will not result in any penalties or loss of benefits to you. The investigators will tell you 
about new information that may affect your willingness to stay in this study.  
 
If you decide not to participate in the study or decide to leave the study early, your decision will not 
affect your relationship with the research team or any other individual at Beth Israel Deaconess 
Medical Center.   
 
INVESTIGATORS RIGHT TO STOP THE STUDY 
The investigators have the right to end your participation in this study if they determine that you no 
longer qualify to take part, or if it would be dangerous for you to continue, or if you do not follow 
study procedures as directed by the investigators.  Beth Israel Deaconess Medical Center or the 
funding source may stop the study at any time. 
 
 
COMMITTEE ON CLINICAL INVESTIGATIONS 
APPROVAL EXPIRATION DATE 
 
01/09/2023


[CCI] Committee on Clinical Investigations 
Page 11 of 18 
 
SUBJECT'S NAME: 
TITLE OF RESEARCH PROTOCOL: A pilot study of the effect of 
prophylactic antibiotics on hospitalized patients with advanced 
cirrhosis   
PRINCIPAL INVESTIGATOR'S NAME: ZACHARY FRICKER, MD 
PROTOCOL #:  2020P000050 
 
 
Informed Consent – Part D 
CCI Form: 12-2018 
PI Revision Date:  1/26/2021 
 
 
 
COSTS AND/OR PAYMENTS TO YOU 
 
COSTS COVERED BY STUDY 
You will not be charged for diagnostic tests required only by virtue of participation in this study or the 
antibiotic or placebo that are part of this research study.  However, you and your insurance company 
will be charged for other tests, procedures or medications of this study that are considered standard 
treatment for your medical condition.  
 
CO-PAYMENT/DEDUCTIBLE STATEMENT 
You will be responsible for any co-payments or deductibles that are standard for your insurance 
coverage.   
 
PAYMENTS TO YOU: 
You will not be paid for participating in this study.  
 
COST OF RESEARCH RELATED INJURY: 
If you are injured as a direct result of your participation in this study you should contact the 
Investigator at the number provided under the section “Whom to Call if You Have Questions” in this 
form.  You will be offered the necessary care to treat your injury.  You or your insurance company 
will be billed for medical care and/or hospitalization related to this injury.  You will be responsible for 
all co-payments and deductibles required under your insurance.  BIDMC will consider 
reimbursement of injury related expenses not covered by your insurance on a case-by-case basis.  
At this time there is no plan to reimburse you for items such as lost wages or lost time from work.  By 
signing this consent form you have not given up any legal rights. 
 
OTHER IMPORTANT INFORMATION  
A description of this clinical trial will be available on www.ClinicalTrials.gov as required by U.S. 
law.  This Web site will not include information that can identify you.  At most, the Web site will 
include a summary of the results.  You can search this Web site at any time. 
 
 
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[CCI] Committee on Clinical Investigations 
Page 12 of 18 
 
SUBJECT'S NAME: 
TITLE OF RESEARCH PROTOCOL: A pilot study of the effect of 
prophylactic antibiotics on hospitalized patients with advanced 
cirrhosis   
PRINCIPAL INVESTIGATOR'S NAME: ZACHARY FRICKER, MD 
PROTOCOL #:  2020P000050 
 
 
Informed Consent – Part D 
CCI Form: 12-2018 
PI Revision Date:  1/26/2021 
 
 
 
AUTHORIZATION FOR USE AND DISCLOSURE OF YOUR PROTECTED HEALTH 
INFORMATION 
As part of this study, we will be collecting, using and sharing with others information about you.  
Please review this section carefully as it contains information about the federal privacy rules and the 
use and disclosure of your information.   
 
DESCRIPTION OF PROTECTED HEALTH INFORMATION [PHI] 
By signing this informed consent document, you are allowing the investigators and other authorized 
personnel to use and disclose health information about you.  This may include information about you 
that already exists (for example: your medical records and other sources of health information, 
demographic information, and the results of any laboratory tests  as well as any new information 
generated as part of this study.  This is your Protected Health Information. 
 
PEOPLE/GROUPS AT BIDMC WHO WILL SHARE AND USE YOUR PROTECTED HEALTH INFORMATION 
Your Protected Health Information may be shared with and used by investigators working on this 
study, including the supporting research team (such as research assistants and coordinators, 
statisticians, data managers, laboratory personnel, pharmacy personnel, and administrative 
assistants), and may also be shared with and used by other health care providers at BIDMC who 
have treated you in the past and have information relevant to the research, or who provide services 
to you in connection with the research.  Your Protected Health Information may also be shared with 
the members and staff of the Committee on Clinical Investigations of Beth Israel Deaconess Medical 
Center, which is responsible for reviewing studies for the protection of the research subjects, so that 
it can carry out its oversight responsibilities with respect to the study.  
PEOPLE/GROUPS OUTSIDE OF BIDMC TO WHOM YOUR PROTECTED HEALTH INFORMATION WILL BE 
DISCLOSED (SHARED) AND WHO MAY USE YOUR PROTECTED HEALTH INFORMATION 
We will take care to maintain confidentiality and privacy about you and your Protected Health 
Information.  We may share your Protected Health Information with the following groups so that they 
may carry out their duties related to this research study: 
 The funding source of this study (American Association for the Study of Liver Diseases 
Foundation) and, where applicable, the people and companies that the sponsor uses to 
oversee, administer, or conduct the research (for example, clinical research organizations are 
companies that are sometimes hired by research sponsors to help manage and run a clinical 
research study) 
 Other research collaborators and supporting research team members taking part in this study  
 Any external health care providers who provide services to you in connection with this 
 
COMMITTEE ON CLINICAL INVESTIGATIONS 
APPROVAL EXPIRATION DATE 
 
01/09/2023


[CCI] Committee on Clinical Investigations 
Page 13 of 18 
 
SUBJECT'S NAME: 
TITLE OF RESEARCH PROTOCOL: A pilot study of the effect of 
prophylactic antibiotics on hospitalized patients with advanced 
cirrhosis   
PRINCIPAL INVESTIGATOR'S NAME: ZACHARY FRICKER, MD 
PROTOCOL #:  2020P000050 
 
 
Informed Consent – Part D 
CCI Form: 12-2018 
PI Revision Date:  1/26/2021 
 
 
 
research 
 Laboratories not affiliated with BIDMC that are involved in conducting tests related to the 
research 
 Statisticians and other data monitors not affiliated with BIDMC 
 Your health insurance company 
 The Food and Drug Administration [FDA], the Department of Health and Human Services 
[DHHS], the National Institute of Health [NIH], the Office for Human Research Protections 
[OHRP], and other federal and state agencies that may have jurisdiction over the research 
 Hospital and Clinical Research Accrediting Agencies 
 
Those who receive your Protected Health Information during the course of the research may not be 
required by the federal privacy regulations to protect it, and they may make further disclosures to 
others and use your information without being subject to penalties under those laws.   
 
PURPOSE: WHY WE ARE USING AND SHARING YOUR PROTECTED HEALTH INFORMATION 
The reason for using and sharing your Protected Health Information is to conduct and oversee the 
current, secondary, and future research described in this Informed Consent Document.  There are 
many other reasons beyond the research for which BIDMC may use or disclose your Protected 
Health Information.  Not all of these reasons require your express written authorization.  For 
example, we will use and share your Protected Health Information to ensure that the research meets 
legal, institutional and accreditation requirements and to conduct public health activities.  The various 
ways in which BIDMC may use and disclose your protected health information without your 
authorization are explained in a document called the Notice of Privacy Practices.  If you have not 
received a copy of BIDMC’s Notice of Privacy Practices, please ask us for one and review it before 
signing this form.  In addition to signing this document, you may also be asked to sign a BIDMC 
General Agreement form acknowledging that you have received the BIDMC Notice of Privacy 
Practices.   
 
NO EXPIRATION DATE – RIGHT TO WITHDRAW AUTHORIZATION 
Your authorization for the use and disclosure of your Protected Health Information in this Study shall 
never expire.  However, you may withdraw your authorization for the use and disclosure of your 
Protected Health Information at any time provided you notify the Principal Investigator in writing.  If 
you would like to take back your authorization so that your Protected Health Information can no 
longer be used in this study, please send a letter notifying the Principal Investigator of your 
withdrawal of your authorization to  
Zachary Fricker, MD; LMOB 8th Floor, 110 Francis St; Brookline Ave., Boston, MA  02215. 
Please be aware that the investigators in this study will not be required to destroy or retrieve any of 
your Protected Health Information that has already been used or disclosed before the Principal 
 
COMMITTEE ON CLINICAL INVESTIGATIONS 
APPROVAL EXPIRATION DATE 
 
01/09/2023


[CCI] Committee on Clinical Investigations 
Page 14 of 18 
 
SUBJECT'S NAME: 
TITLE OF RESEARCH PROTOCOL: A pilot study of the effect of 
prophylactic antibiotics on hospitalized patients with advanced 
cirrhosis   
PRINCIPAL INVESTIGATOR'S NAME: ZACHARY FRICKER, MD 
PROTOCOL #:  2020P000050 
 
 
Informed Consent – Part D 
CCI Form: 12-2018 
PI Revision Date:  1/26/2021 
 
 
 
Investigator receives your letter, and they are permitted to continue to use and disclose your 
previously collected information as necessary to complete the research. 
 
 
COMMITTEE ON CLINICAL INVESTIGATIONS 
APPROVAL EXPIRATION DATE 
 
01/09/2023


[CCI] Committee on Clinical Investigations 
Page 15 of 18 
 
SUBJECT'S NAME: 
TITLE OF RESEARCH PROTOCOL: A pilot study of the effect of 
prophylactic antibiotics on hospitalized patients with advanced 
cirrhosis   
PRINCIPAL INVESTIGATOR'S NAME: ZACHARY FRICKER, MD 
PROTOCOL #:  2020P000050 
 
 
Informed Consent – Part D 
CCI Form: 12-2018 
PI Revision Date:  1/26/2021 
 
 
 
REFUSAL TO SIGN 
Your clinical treatment may not be conditioned upon whether you sign the Authorization for 
Research. However, if you choose not to sign this informed consent document and authorization for 
the use and disclosure of your Protected Health Information, you will not be allowed to take part in 
the research study. 
 
RIGHT TO ACCESS AND COPY YOUR PHI 
If you wish to review or copy your Protected Health Information as it is made part of your medical 
record, you may do so after the completion or termination of the study by sending a letter to the 
Principal Investigator requesting a copy of your Protected Health Information.  You may not be 
allowed to inspect or copy your Protected Health Information until this study is completed or 
terminated. 
 
ADDITIONAL CONTACT FOR QUESTIONS OR CONCERNS 
You may contact the Human Subjects Protection Office at [617] 975-8500 in the event that you 
would like to obtain information or to offer input about the research study.  This office is independent 
of the investigator or investigator’s research staff and can also assist with questions relating to your 
rights as a participant in research, which may include questions, concerns or complaints about your 
participation in the study. 
 
 
COMMITTEE ON CLINICAL INVESTIGATIONS 
APPROVAL EXPIRATION DATE 
 
01/09/2023


[CCI] Committee on Clinical Investigations 
Page 16 of 18 
 
SUBJECT'S NAME: 
TITLE OF RESEARCH PROTOCOL: A pilot study of the effect of 
prophylactic antibiotics on hospitalized patients with advanced 
cirrhosis   
PRINCIPAL INVESTIGATOR'S NAME: ZACHARY FRICKER, MD 
PROTOCOL #:  2020P000050 
 
 
Informed Consent – Part D 
CCI Form: 12-2018 
PI Revision Date:  1/26/2021 
 
 
 
THE FOLLOWING PARAGRAPHS CONTAIN SOME STANDARD INFORMATION WHICH 
GENERALLY APPLIES TO INDIVIDUALS PARTICIPATING IN A RESEARCH STUDY. 
 
CONSENT FORM FOR CLINICAL RESEARCH 
I have read the previous page[s] of the consent form and the investigator has explained the details of the 
study.  I understand that I am free to ask additional questions. 
 
If I wish additional information regarding this research and my rights as a research subject, or if I believe I 
have been harmed by this study, I may contact the Human Subjects Protection Office (HSPO). 
 
I am aware that this is a research project and that unforeseen side effects may occur. 
 
I understand that the Beth Israel Deaconess Medical Center has no formal program for compensating patients 
for medical injuries arising from this research.  Medical treatment will be provided for injuries at the usual 
charge to me or to my insurer unless payment is otherwise provided for in this consent form. 
 
I understand that participation in this study is voluntary and I may refuse to participate or may discontinue 
participation at any time without penalty, loss of benefits, or prejudice to the quality of care which I will receive. 
 
I acknowledge that no guarantees have been made to me regarding the results of the treatment involved in 
this study, and I consent to participate in the study and have been given a copy of this form. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Signature of Subject or Legally Authorized Representative  
Date 
(Parent if the subject is a minor) 
 
 
 
 
 
 
 
 
 
 
 
 
Relationship of Legally Authorized Representative to Subject   
 
 
The subject has been given the opportunity to read this consent form and to ask questions before signing, and 
has been given a copy. 
 
___________________________________________________________ 
SIGNATURE OF INVESTIGATOR/Co-Investigator   
DATE 
 
__________________________________________________________ 
PRINT INVESTIGATOR’S/Co-Investigator’s  
NAME 
 
A signing co-investigator must be listed on the study’s approved Research Staffing Form at the time of consent. 
 
 
 
COMMITTEE ON CLINICAL INVESTIGATIONS 
APPROVAL EXPIRATION DATE 
 
01/09/2023


[CCI] Committee on Clinical Investigations 
Page 17 of 18 
 
SUBJECT'S NAME: 
TITLE OF RESEARCH PROTOCOL: A pilot study of the effect of 
prophylactic antibiotics on hospitalized patients with advanced 
cirrhosis   
PRINCIPAL INVESTIGATOR'S NAME: ZACHARY FRICKER, MD 
PROTOCOL #:  2020P000050 
 
 
Informed Consent – Part D 
CCI Form: 12-2018 
PI Revision Date:  1/26/2021 
 
 
 
 
VERBAL CONSENT PROCEDURES WITH LEGALLY AUTHORIZED REPRESENTATIVE  
 
If consenting over the phone ask the LAR: 
Do you have any questions or concerns before you provide consent on behalf of the patient? If you would like 
some time to think about this, please let me know and we can arrange another time to talk.  
 
If LAR consents: Thank you.   
 
 
TO BE FILLED OUT BY RESEARCH STAFF  
 
LAR provided verbal consent for the patient to participate in the study  
 
LAR declined to provide consent for the patient to participate in the study  
 
 
_________________________________________________________________ 
PRINT LEGALLY AUTHORIZED REPRESENTATIVE’S NAME     
 
_________________________________________________________________ 
RELATIONSHIP OF LEGALLY AUTHORIZED REPRESENTATIVE TO SUBECT 
 
 
_________________________________________________________________ 
PRINT INVESTIGATOR’S/Co-Investigator’s NAME 
_________________________________________________________________ 
SIGNATURE OF INVESTIGATOR/Co-Investigator                              DATE 
 
 
 
Gave verbal consent form to Legally Authorized Representative: 
 
In person                                  Mail                                  Email/text                                    
 
 
 
 
 
 
 
 
 
COMMITTEE ON CLINICAL INVESTIGATIONS 
APPROVAL EXPIRATION DATE 
 
01/09/2023


[CCI] Committee on Clinical Investigations 
Page 18 of 18 
 
SUBJECT'S NAME: 
TITLE OF RESEARCH PROTOCOL: A pilot study of the effect of 
prophylactic antibiotics on hospitalized patients with advanced 
cirrhosis   
PRINCIPAL INVESTIGATOR'S NAME: ZACHARY FRICKER, MD 
PROTOCOL #:  2020P000050 
 
 
Informed Consent – Part D 
CCI Form: 12-2018 
PI Revision Date:  1/26/2021 
 
 
 
THE FOLLOWING SECTIONS ARE NOT NEEDED FOR ALL STUDIES AND SHOULD BE 
UTILIZED AS INDICATED: 
 
If the subject is able to speak and understand English but is not able to read or write  
 
I was present during the entire oral presentation of the informed consent and witnessed the subject’s agreement to 
participate in the study. 
 
Signature of Witness:  
 
Printed Name of Witness:  
 
Date:   
 
 
If the subject is able to understand English but is not physically able to read or write or see 
 
I was present during the entire oral presentation of the informed consent and witnessed the subject’s agreement to 
participate in the study. 
 
Signature of Witness:  
 
Printed Name of Witness:  
 
Date:   
 
 
 
If the subject is not English speaking and signed the translated Short Form in lieu of the English consent 
document. 
As someone who understands both English and the language spoken by the subject, I interpreted, in the subject’s 
language, the researcher’s presentation of the English consent form.  The subject was given the opportunity to ask 
questions.  
Signature of Interpreter:  
 
Printed name of Interpreter:  
 
Date:  
 
 
 
COMMITTEE ON CLINICAL INVESTIGATIONS 
APPROVAL EXPIRATION DATE 
 
01/09/2023