Clinical trial NCT03372941
Conditions: Skin Infection
Keywords: Acute bacterial skin and skin structure infections Hospital avoidance Antibiotic therapy Dalbavancin Emergency department
Sponsor: Washington University School of Medicine
Start date: 2019-03-04; Completion date: 2021-10-14
Enrollment: 11 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
More than 40% of patients presenting with acute bacterial skin and skin structure infection (ABSSSI) to the Barnes-Jewish Hospital (BJH) emergency department (ED) are admitted for intravenous antibiotics. There is growing evidence to suggest that many hospital admissions for uncomplicated ABSSSI due to Gram-positive bacteria could be avoided with an alternative treatment strategy employing newer long-acting antibiotics. Coupled with close outpatient follow-up, such an alternative hospital avoidance strategy has the potential to improve quality and value of care for patients with uncomplicated ABSSSI and optimize use of limited inpatient healthcare resources.

Detailed description:
This study seeks to establish the feasibility and acceptability of an alternative treatment strategy for uncomplicated acute bacterial skin and skin structure infection (ABSSSI) in the Barnes Jewish Hospital (BJH) Emergency Department (ED) focusing on hospital admission avoidance using single-dose, long-acting antimicrobial therapy complemented by close follow-up in the ambulatory setting. The extended half-life of these new antimicrobials (dalbavancin, oritavancin) allows for an effective treatment course of \>7 days with a single dose, which is the accepted duration for which ABSSSI is usually treated with daily doses of other intravenous or oral antimicrobials. The investigators believe that such an approach will conserve hospital resources by reducing admissions for uncomplicated ABSSSI while delivering comparable if not superior care for this disease, allowing optimal utilization of BJH inpatient beds for other serious medical conditions requiring inpatient care. The investigators believe this novel alternative approach will allow hospitals such as BJH to more cost-effectively and efficiently manage ABSSSI patients. This study will reduce the number of \>2 midnight observation admissions to BJH for ABSSSI, thereby improving inpatient capacity to care for patients requiring \>2 midnight hospital inpatient admission.

The investigators will conduct a randomized controlled trial comparing patients treated with a single-dose of intravenous dalbavancin (an antibiotic that has been FDA-approved for the treatment of ABSSSI and is currently being used in clinical practice in the U.S.) and discharged home from the ED with close ambulatory care follow-up in clinic vs. patients treated with "usual care" (hospital admission for multiple doses of intravenous vancomycin or other antibiotic directed towards Gram-positive bacteria). Clinical outcomes, healthcare utilization, hospital costs, and patient satisfaction will be evaluated.

Arms: arm 1: Patient will receive a single dose of dalbavancin administered in the BJH ED or ED observation unit for ABSSSI followed by discharge w/ close Infectious Disease outpatient clinic follow-up. arm 2: Patients will receive "usual care" (i.e., hospital admission for intravenous antibiotics - typically, vancomycin) - antibiotic and doses to be determined at the discretion of the treating clinician (both in the BJH ED and on the BJH inpatient ward).
Interventions: intervention 1: Dalbavancin
Intervention descriptions: intervention 1: Dalbavancin, a lipoglycopeptide antibiotic, has been approved by the FDA for the treatment of ABSSSI caused by Gram-positive bacteria. A single dose of dalbavancin will be administered in the Emergency Department followed by discharge with close outpatient infectious disease clinic follow-up.

Protocol documents:
Prot_SAP_000.pdf: 
 
 
 
 
 
 
______________________________________________________________________________________ 
 
1 
 
 
 
Hospital Avoidance Strategies for Treatment of Acute Bacterial 
Skin and Skin Structure Infections (ABSSSI) 
 
 
Principal Investigator:   
Stephen Y. Liang, MD, MPHS 
 
 
 
 
 
 
Version Date:  
MAY 28, 2019 
 


 
 
 
 
 
 
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2 
 
TABLE OF CONTENTS 
 
A 
INTRODUCTION ............................................................................................................................... 4 
A1 
STUDY ABSTRACT ......................................................................................................................... 4 
A2 
PRIMARY HYPOTHESIS ................................................................................................................... 4 
A3 
PURPOSE OF THE STUDY PROTOCOL .............................................................................................. 4 
B 
BACKGROUND .................................................................................................................................. 4 
B1 
PRIOR LITERATURE AND STUDIES .................................................................................................. 4 
B2 
RATIONALE FOR THIS STUDY ......................................................................................................... 5 
C 
STUDY OBJECTIVES........................................................................................................................ 5 
C1 
PRIMARY AIM ................................................................................................................................ 6 
C2 
SECONDARY AIM ....................................................................ERROR! BOOKMARK NOT DEFINED. 
C3 
RATIONALE FOR THE SELECTION OF OUTCOME MEASURES ........................................................... 6 
D 
INVESTIGATIONAL AGENT .......................................... ERROR! BOOKMARK NOT DEFINED. 
D1 
PRECLINICAL DATA ................................................................ERROR! BOOKMARK NOT DEFINED. 
D2 
CLINICAL DATA TO DATE .......................................................ERROR! BOOKMARK NOT DEFINED. 
D3 
DOSE RATIONALE AND RISK/BENEFITS ..................................ERROR! BOOKMARK NOT DEFINED. 
E 
STUDY DESIGN ................................................................................................................................. 6 
E1 
OVERVIEW OR DESIGN SUMMARY ................................................................................................. 6 
E2 
SUBJECT SELECTION AND WITHDRAWAL....................................................................................... 7 
2.a 
Inclusion Criteria ..................................................................................................................... 7 
2.a 
Exclusion Criteria ..................................................................................................................... 7 
2.b 
Ethical Considerations ............................................................................................................. 8 
2.c 
Subject Recruitment Plans and Consent Process ..................................................................... 8 
2.d 
Randomization Method and Blinding ....................................................................................... 8 
2.e 
Risks and Benefits ..................................................................................................................... 8 
2.f 
Early Withdrawal of Subjects ................................................................................................... 9 
2.g 
When and How to Withdraw Subjects ....................................................................................... 9 
2.h 
Data Collection and Follow-up for Withdrawn Subjects .......................................................... 9 
E3 
STUDY DRUG ................................................................................................................................. 9 
3.a 
Description ............................................................................................................................... 9 
3.b 
Treatment Regimen ................................................................................................................... 9 
3.c 
Method for Assigning Subjects to Treatment Groups ............................................................... 9 
3.d 
Preparation and Administration of Study Drug ........................................................................ 9 
3.e 
Subject Compliance Monitoring ..............................................................................................10 
3.f 
Prior and Concomitant Therapy ................................................ Error! Bookmark not defined. 
3.g 
Packaging .................................................................................. Error! Bookmark not defined. 
3.h 
Blinding of Study Drug ............................................................................................................10 
3.i 
Receiving, Storage, Dispensing and Return ............................................................................10 
F 
STUDY PROCEDURES ....................................................................................................................10 
F1 
SCREENING FOR ELIGIBILITY ........................................................................................................10 
F2 
SCHEDULE OF MEASUREMENTS ....................................................................................................10 
F3 
VISIT 1 ....................................................................................ERROR! BOOKMARK NOT DEFINED. 


 
 
 
 
 
 
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3 
F4 
VISIT 2 ETC. ............................................................................ERROR! BOOKMARK NOT DEFINED. 
F5 
SAFETY AND ADVERSE EVENTS ....................................................................................................11 
5.a 
Safety and Compliance Monitoring .........................................................................................11 
5.b 
Medical Monitoring .................................................................................................................11 
i 
Investigator only ..................................................................................................................................... 11 
ii 
Independent expert to monitor ................................................................. Error! Bookmark not defined. 
iii 
Institutional Data and Safety Monitoring Board ..................................................................................... 12 
iv 
Independent Data and Safety Monitoring Board ...................................... Error! Bookmark not defined. 
5.c 
Definitions of Adverse Events ..................................................................................................12 
5.d 
Classification of Events ...........................................................................................................12 
i 
Relationship ............................................................................................................................................ 12 
ii 
Severity ................................................................................................................................................... 13 
iii 
Expectedness .......................................................................................................................................... 13 
5.e 
Data Collection Procedures for Adverse Events .....................................................................13 
5.f 
Reporting Procedures ................................................................ Error! Bookmark not defined. 
5.g 
Adverse Event Reporting Period ................................................ Error! Bookmark not defined. 
5.h 
Post-study Adverse Event .......................................................... Error! Bookmark not defined. 
F6 
STUDY OUTCOME MEASUREMENTS AND ASCERTAINMENT ..........................................................14 
G 
STATISTICAL PLAN ........................................................................................................................14 
G1 
SAMPLE SIZE DETERMINATION AND POWER .................................................................................14 
G2 
INTERIM MONITORING AND EARLY STOPPING ..............................................................................15 
G3 
ANALYSIS PLAN............................................................................................................................15 
G4 
STATISTICAL METHODS ................................................................................................................15 
G5 
MISSING OUTCOME DATA ......................................................ERROR! BOOKMARK NOT DEFINED. 
G6 
UNBLINDING PROCEDURES .....................................................ERROR! BOOKMARK NOT DEFINED. 
H 
DATA HANDLING AND RECORD KEEPING .............................................................................15 
H1 
CONFIDENTIALITY AND SECURITY ................................................................................................15 
H2 
TRAINING......................................................................................................................................16 
H3 
CASE REPORT FORMS AND SOURCE DOCUMENTS ...................ERROR! BOOKMARK NOT DEFINED. 
H4 
RECORDS RETENTION .............................................................ERROR! BOOKMARK NOT DEFINED. 
H5 
PERFORMANCE MONITORING .................................................ERROR! BOOKMARK NOT DEFINED. 
I 
STUDY MONITORING, AUDITING, AND INSPECTING .............. ERROR! BOOKMARK NOT 
DEFINED. 
I1 
STUDY MONITORING PLAN .....................................................ERROR! BOOKMARK NOT DEFINED. 
I2 
AUDITING AND INSPECTING ....................................................ERROR! BOOKMARK NOT DEFINED. 
J 
STUDY ADMINISTRATION ...........................................................................................................16 
J1 
ORGANIZATION AND PARTICIPATING CENTERS ......................ERROR! BOOKMARK NOT DEFINED. 
J2 
FUNDING SOURCE AND CONFLICTS OF INTEREST ..........................................................................16 
J3 
COMMITTEES ..........................................................................ERROR! BOOKMARK NOT DEFINED. 
J4 
SUBJECT STIPENDS OR PAYMENTS ................................................................................................16 
J5 
STUDY TIMETABLE .................................................................ERROR! BOOKMARK NOT DEFINED. 
K 
PUBLICATION PLAN ......................................................................................................................16 
L 
ATTACHMENTS ................................................................ ERROR! BOOKMARK NOT DEFINED. 
L1 
TABLES ...................................................................................ERROR! BOOKMARK NOT DEFINED. 
L2 
INFORMED CONSENT DOCUMENTS...........................................ERROR! BOOKMARK NOT DEFINED. 
L3 
PATIENT EDUCATION BROCHURES...........................................ERROR! BOOKMARK NOT DEFINED. 
L4 
SPECIAL PROCEDURES PROTOCOLS .........................................ERROR! BOOKMARK NOT DEFINED. 
L5 
QUESTIONNAIRES OR SURVEYS ...............................................ERROR! BOOKMARK NOT DEFINED. 
M 
REFERENCES ...................................................................................................................................16 


 
 
 
 
 
 
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4 
 
A Introduction 
 
A1 Study Abstract 
More than 40% of patients presenting with acute bacterial skin and skin structure infection 
(ABSSSI) to the Barnes-Jewish Hospital (BJH) emergency department (ED) are admitted for 
intravenous antibiotics.  There is growing evidence to suggest that many hospital admissions for 
uncomplicated ABSSSI due to Gram-positive bacteria could be avoided with an alternative 
treatment strategy employing newer long-acting antibiotics.  Coupled with close outpatient 
follow-up, such an alternative hospital avoidance strategy has the potential to improve quality 
and value of care for patients with uncomplicated ABSSSI and optimize use of limited inpatient 
healthcare resources. 
 
A2 Primary Hypothesis 
Patients with uncomplicated ABSSSI suspected to be due to Gram-positive bacteria treated using 
an alternative strategy consisting of single-dose dalbavancin and close outpatient follow-up will 
have lower healthcare service utilization, lower healthcare-associated costs, greater patient 
satisfaction, and comparable safety compared to “usual care” (hospital admission for 
intravenous antibiotics) at BJH.  
 
A3 Purpose of the Study Protocol 
Conduct a single center, randomized controlled study to compare healthcare service utilization, 
healthcare-associated costs, patient satisfaction, patient safety, and clinical outcomes in BJH ED 
patients with uncomplicated ABSSSI  suspected to be due to Gram-positive bacteria treated with 
single-dose dalbavancin (alternative strategy) vs. hospital admission for intravenous antibiotics 
(“usual care”). 
 
B Background 
 
B1 Prior Literature and Studies 
Acute bacterial skin and skin structure infections (ABSSSI), including cellulitis, erysipelas, wound 
infections, and major cutaneous abscesses, are routinely treated in the emergency department 
(ED).  Cellulitis ranks third behind only chest pain and asthma as the most common reason 
patients seek care in the ED.  Nationwide, nearly 20% of ABSSSI patients evaluated in EDs are 
admitted to the hospital to receive intravenous antimicrobial therapy, contributing 870,000 
hospital admissions a year at a cost of more than $6 billion in charges annually [1].  While 
hospital admission is necessary for patients with life-threatening infection, significant medical 
comorbidities, or other concurrent acute illness, mounting evidence suggests that a substantial 
number of ABSSSI patients are unnecessarily admitted or are admitted for longer than 


 
 
 
 
 
 
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5 
necessary durations to receive intravenous antimicrobial therapy [2].  If we consider that the 
average national inpatient length of stay for cellulitis (the most common form of ABSSSI) is 3.97 
days at an average cost of more than $6,000 per patient, it becomes clear that the management 
of ABSSSI currently utilizes significant inpatient healthcare resources.  Decisions to admit or 
discharge a patient with ABSSSI in the ED are often based on physician preference, which may 
be influenced by patient expectations as well as the perceived likelihood of whether the patient 
will adhere to outpatient antimicrobial therapy and/or complete timely follow-up in the 
ambulatory setting.  Novel alternative treatment strategies focused on hospital admission 
avoidance taking into account these practical considerations have the potential to improve 
the quality and value of care for patients presenting to the ED with uncomplicated ABSSSI. 
 
While vancomycin is most frequently used in the ED and inpatient setting to empirically treat 
ABSSSI suspected to be caused by Gram-positive bacteria (e.g., methicillin-sensitive and -
resistant Staphylococcus aureus, Streptococcus pyogenes, Enterococcus faecalis), this antibiotic 
must be administered multiple times at regular intervals over a course of therapy through an 
intravenous catheter.  Challenges achieving and maintaining therapeutic serum drug levels 
coupled with the potential for renal toxicity and catheter-associated bloodstream infections can 
adversely impact patient care. 
 
Dalbavancin, a novel lipoglycopeptide antibiotic, has been approved by the FDA for the 
treatment of ABSSSI caused by Gram-positive bacteria.  Once-weekly intravenous dalbavancin 
has been shown to be non-inferior to twice-daily intravenous vancomycin followed by oral 
linezolid for treatment of ABSSSI over a 10-14 day course of therapy [3].  Furthermore, a single 
1500 mg infusion of dalbavancin has been demonstrated to be non-inferior to a 2-dose regimen 
for treatment of ABSSSI with comparable safety profile [4].  The extended half-life of 
dalbavancin therefore allows for an effective treatment course of >7 days with a single dose, the 
accepted duration of therapy for uncomplicated ABSSSI.  Dalbavancin is currently being used in 
clinical practice across the U.S. to treat ABSSSI. 
 
B2 Rationale for this Study 
At Barnes-Jewish Hospital (BJH), almost 40% of the more than 200 ABSSSI patients evaluated 
monthly in our ED are admitted for inpatient antibiotic therapy.  Close collaborations between 
the Divisions of Emergency Medicine and Infectious Diseases at Washington University School of 
Medicine provide a robust infrastructure to implement and study an alternative treatment 
strategy incorporating single-dose administration of dalbavancin in the ED followed by close 
outpatient follow-up in the Washington University Infectious Disease Clinic. 
 
We believe that such an approach will conserve hospital resources by reducing admissions for 
uncomplicated ABSSSI while delivering comparable if not superior care for this disease, allowing 
optimal utilization of BJH inpatient beds for other serious medical conditions requiring inpatient 
care.  We believe this novel alternative approach will allow hospitals such as BJH to more cost-
effectively and efficiently manage ABSSSI patients.  This study will reduce the number of >2 
midnight observation admissions to BJH for ABSSSI, thereby improving inpatient capacity to care 
for patients requiring >2 midnight hospital inpatient admission. 
 


 
 
 
 
 
 
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6 
C Study Objectives 
 
C1 Primary Aim 
Implement a study protocol within the BJH ED to treat uncomplicated ABSSSI patients 
comparing a novel alternative treatment strategy (single-dose intravenous dalbavancin) with 
close outpatient follow-up vs. “usual care” (hospital admission for multiple doses of intravenous 
antibiotic) with relation to the following outcomes: 
- 
Healthcare service utilization (e.g., ED length-of-stay, inpatient length-of-stay, ED 
revisits, need for inpatient admission/readmission) 
- 
Healthcare-associated costs 
- 
Patient satisfaction [including completion of items from the Hospital Consumer 
Assessment of Healthcare Providers and Systems (HCAHPS) survey and a targeted set of 
questions specific to ABSSSI care] 
- 
Patient safety (e.g., adverse drug events, laboratory testing for drug-associated toxicity) 
- 
Clinical outcomes (e.g., change in size of ABSSSI lesion, resolution of symptoms, need for 
additional intravenous/oral antibiotic therapy) 
 
C2 Rationale for the Selection of Outcome Measures 
Existing data on healthcare service utilization and cost related to the use of new long-acting 
antibiotics to treat uncomplicated ABSSSI are limited to economic modeling [5-7].  Real-world 
data describing these outcomes from a randomized, controlled study do not exist to the best of 
our knowledge.  Likewise, little if any data exists comparing patient satisfaction between those 
receiving long-acting antibiotics vs. usual care.  Patient safety and clinical outcomes data have 
been reported in previous large randomized controlled trials [3, 4]. 
 
D Study Design  
 
D1 Overview or Design Summary 
This study will be single center, randomized, non-blinded study comparing two active treatment 
arms to treat uncomplicated ABSSSI suspected to be due to Gram-positive bacteria: 
 
- 
Alternative treatment strategy comprised of a single dose of dalbavancin administered 
in the BJH ED or ED observation unit followed by discharge w/ close Infectious Disease 
outpatient clinic follow-up 
   vs. 
- 
“Usual care” (i.e., hospital admission for intravenous antibiotics – typically, vancomycin) 
– antibiotic and doses to be determined at the discretion of the treating clinician (both 
in the BJH ED and on the BJH inpatient ward) 
 
Initial patient recruitment, randomization, and data collection (including patient demographics, 
clinical measures, physical examination, adverse drug monitoring, patient satisfaction) will be 


 
 
 
 
 
 
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7 
conducted by research coordinators and faculty from the Washington University Emergency 
Care Research Core (ECRC) while the patient is in the BJH ED on Day 1.  Patients in the “usual 
care” arm will continue to be followed by the ECRC during their inpatient hospital stay.  
 
Patients in the alternative treatment strategy arm discharged from the BJH ED will receive in-
person outpatient follow-up (including assessment of clinical measures, adverse drug 
monitoring, patient satisfaction) in the Washington University Infectious Disease Clinic 
(specifically the Infectious Disease Clinical Research Unit, or ID-CRU, co-located within the 
Infectious Disease Clinic) between Day 3 and Day 7.  This in-person follow-up will be conducted 
by an infectious disease specialist (either the PI or sub-PI) in concert with research coordinators 
from the ID-CRU.  Telephone follow-up for these patients focusing on healthcare utilization and 
patient satisfaction will occur at Day 14 and Day 28. 
 
Patients in the “usual care” arm will receive in-person follow-up during their hospital admission 
or in the ID-CRU between Day 3 and Day 7, with the same evaluation as the alternative 
treatment strategy arm.  Telephone follow-up will likewise occur at Day 14 and Day 28. 
 
Additional information on study outcome measures related to management of their 
uncomplicated ABSSSI through Day 28 will be obtained from review of patient electronic health 
records and BJH healthcare cost/financial data. 
 
D2 Subject Selection and Withdrawal  
 
2.a 
Inclusion Criteria  
- 
Adult (age ≥18 years) 
- 
Diagnosis of uncomplicated ABSSSI suspected to be due to Gram-positive bacteria by 
treating ED clinician, with presence of the following: 
o Skin lesion size ≥75 cm2 (measured by area of erythema, edema, and/or 
induration) 
   AND 
o Signs of systemic inflammation (at least 1 of the following: WBC >12,000 or 
<4,000 cells/mm3; ≥10% immature neutrophils on peripheral smear; 
temperature >38.3˚C or <36˚C; heart rate >90 bpm, respiratory rate >20 bpm).  
Signs of systemic inflammation not required if the patient is age >70 years, has 
diabetes mellitus, or has been treated with immunosuppressive or 
chemotherapy in the past 90 days. 
- 
Clinical determination by treating ED clinician that patient will need hospital admission 
for the sole purpose of receiving intravenous antibiotics directed only towards Gram-
positive bacteria (e.g., vancomycin, cefazolin) to treat uncomplicated ABSSSI 
2.a 
Exclusion Criteria  
- 
Risk for ABSSSI due to Gram-negative bacteria (neutropenia with absolute neutrophil 
count <500 cells/µL, HIV or severely immunocompromised, burns, infection after 
trauma or as a result of an aquatic environment, infection after skin graft) 
- 
Any abscess requiring operative drainage 


 
 
 
 
 
 
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8 
- 
Infection due to a vascular catheter or prosthetic device 
- 
Infection of a diabetic foot ulcer or decubitus ulcer 
- 
Necrotizing soft tissue infection 
- 
Sepsis (quick SOFA score ≥2) or septic shock (requiring vasopressors to maintain mean 
arterial pressure ≥65 mmHg despite resuscitation with at least 30mL/kg of IV crystalloid 
within first 3 hours) 
- 
Hypersensitivity to glycopeptides (vancomycin, televancin, dalbavancin, oritavancin) 
- 
Severe renal insufficiency (CrCl <30 mL/min) 
- 
Severe hepatic insufficiency (Child-Pugh Class C) 
- 
Pregnant or nursing 
2.b 
Ethical Considerations  
Dalbvancin has been approved by the FDA for the treatment of ABSSSI due to Gram-positive 
bacteria and is currently being used in clinical practice in the U.S.  Therefore, both the 
alternative treatment strategy and “usual care” strategy represent accepted medical therapies 
to treat ABSSSI.  
2.c 
Subject Recruitment Plans and Consent Process 
All patients approached for participation in the study will have a diagnosis or clinical impression 
made by the treating ED clinician of uncomplicated ABSSSI suspected to be due to Gram-positive 
bacteria requiring intravenous antimicrobial therapy and hospital admission for this sole 
purpose.  The patient will be approached for participation in the ED treatment room to maintain 
privacy to discuss the study.  The investigators will discuss with the patient that there is a study 
being conducted in the BJH ED that they may qualify for that involves using either a single dose 
of a new FDA-approved long-acting antibiotic (dalbavancin) followed by discharge home or 
admission to the hospital for "usual care" (multiple doses of intravenous antibiotics).  They will 
be informed that the newer long-acting antibiotics have been found to be non-inferior to "usual 
care" in the treatment of ABSSSI.  Patients will be informed about the potential side effects they 
may experience by receiving these medications.  Patients randomized to receive dalbavancin 
will be told that they may opt out of the study at any point in time if they think they are not 
getting appropriate treatment for their ABSSSI, defaulting to hospital admission for "usual care". 
2.d 
Randomization Method and Blinding 
Patients will be randomized using a random number generator.  Patients with an odd number 
will receive the single-dose long-acting antibiotic, dalbavancin, in the BJH ED.  Those with an 
even number will receive “usual care” with intermittent intravenous antibiotics at the discretion 
of the treating ED clinician and inpatient physician upon hospital admission.  This study will not 
involve blinding. 
2.e 
Risks and Benefits 
Patients receiving dalbavancin may be at risk for flushing, headache, rash, nausea, vomiting, 
diarrhea, or other allergic reaction.  Nausea is the most common side effect of dalbavancin and 
adverse drug events range anywhere from 1-10%. 
 
Vancomycin, a standard antibiotic used to treat most Gram-positive bacterial infections, may 
cause hypotension, flushing, red man syndrome, phlebitis, rash, or nephrotoxicity in some cases.  


 
 
 
 
 
 
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9 
The side effects of vancomycin and other standard antibiotics (e.g., cefazolin) are well-known to 
clinicians given their widespread day-to-day use in the hospital. 
 
For patients receiving dalbavancin, the benefits of participating in the study include avoidance 
of hospital admission and receipt of this antibiotic at no cost.  They will also benefit from 
frequent clinical monitoring both in the ED and outpatient clinic setting.  These patients may 
also benefit from higher satisfaction and comfort at being able to recover from their illness at 
home rather than in the hospital, eliminating the need for frequent blood tests, intravenous 
infusions, and prolonged convalescence in bed, as well as the risk for healthcare-associated 
infections (e.g., phlebitis, central venous catheter infection, pneumonia).  They may also have 
reduced healthcare costs overall. 
 
Patients receiving “usual care” will have the benefit of longer direct observation in the hospital. 
2.f 
Early Withdrawal of Subjects  
Patients may withdraw from the study at any time.  Patients who experience an adverse drug 
event requiring termination of dalbavancin infusion in the ED prior to administration of the full 
dose will be withdrawn from the study.  Patients may opt out of the study at any point in 
time if they think they are not getting appropriate treatment for their ABSSSI, defaulting 
to hospital admission for "usual care". 
2.g 
When and How to Withdraw Subjects  
Patients and/or family members designated as power of attorney may provide verbal or written 
notification of their intent to withdraw from the study at any time. 
2.h 
Data Collection and Follow-up for Withdrawn Subjects  
No additional data will be collected from patients that have withdrawn from the study. 
 
D3 Study Drug  
 
3.a 
Description  
The study drug, dalbavancin, is a novel lipoglycopeptide that has been approved by the FDA for 
the treatment of ABSSSI due to Gram-positive bacteria.  It will be administered to patients 
randomized to the alternative treatment strategy arm. 
3.b 
Treatment Regimen  
Alternative treatment strategy arm:  Single 1500mg intravenous dose of dalbavancin, 
administered over a 30-minute time period. 
 
“Usual care” arm:  Antibiotic selection, duration, and frequency of administration will be 
decided  at the discretion of the treating ED and inpatient care clinician. 
3.c 
Method for Assigning Subjects to Treatment Groups  
Random number generator, conducted by the ECRC research coordinator. 


 
 
 
 
 
 
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10
3.d 
Preparation and Administration of Study Drug 
Dalbavancin is supplied in single-use vials containing 500mg of the drug in sterile powder form.  
In accordance with the package insert for dalbavancin, each 500mg vial must be reconstituted 
with either 25 mL of sterile water for injection, USP, or 5% dextrose injection, USP.  After slow 
addition of either injection, the vial should be gently rolled to ensure all surfaces containing 
dalbavancin have been wetted.  Alternatively, brief, gentle swirling with inversion of the vial can 
also be performed to dissolve the dalbavancin.  Each reconstituted vial will contain 20mg/mL of 
dalbavancin. 
 
Prior to administration, the reconstituted vial(s) of dalbavancin must be further diluted into a 
250mL bag of 5% dextrose for injection, USP, for a final concentration of 1 mg/mL to 5 mg/mL. 
 
Dalbavancin should be administered via intravenous infusion, using a total infusion time of 30 
minutes. 
 
Dalbavancin should not be co-infused with other medications or electrolytes.  Saline-based 
infusion solutions may cause precipitation and should not be used.  If a common intravenous 
line is being used to administer other drugs in addition to dalbavancin, the line should be 
flushed before and after each dalbvancin infusion with 5% dextrose injection, USP. 
3.e 
Subject Compliance Monitoring  
Administration of dalbavancin will occur in the BJH ED under the supervision of the research 
team and treating clinical staff. 
3.f 
Blinding of Study Drug  
Blinding of study drug will not be performed in this study. 
3.g 
Receiving, Storage, Dispensing and Return  
Dalbavancin doses will be stored in the BJH Research Pharmacy.   
 
When a patient has been identified and randomized to the alternative treatment strategy arm, a 
single 1500 mg dose of dalbavancin will be reconstituted in and released from the BJH Research 
Pharmacy to the BJH ED for study patient use. 
 
E Study Procedures  
 
E1 Screening for Eligibility 
Patients diagnosed with uncomplicated ABSSSI suspected to be due to Gram-positive bacteria in 
the BJH ED and felt by the treating clinician to require hospital admission for intravenous 
antibiotics alone will be approached for participation in the study by ECRC research 
coordinators.  ECRC will use a combination of electronic medical record review and query by 
CASE-ED (Computer-Assisted Subject Enrollment for the ED) (HRPO #201106074), a software 
system that automatically captures and screens ED clinical data in the electronic medical record. 


 
 
 
 
 
 
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11
E2 Schedule of Measurements 
- 
Day 1 (BJH ED) – in-person 
o Patient demographics (e.g., age, sex, race, payor/insurance status, history of 
substance dependence, lack of housing) 
o Clinical characteristics (comorbid diseases, prior/current medications including 
antibiotics, signs/symptoms associated with ABSSSI, measurement of lesion size, 
Eron severity classification, vital signs, ED laboratory data) 
o Adverse drug events associated with antibiotic(s) received in the BJH ED 
o Patient satisfaction & quality of life measures 
 
- 
Day 3 to Day 7 (ID Clinic/ID-CRU or BJH) – in-person 
o Self-reported healthcare utilization 
o Clinical characteristics (signs/symptoms associated with ABSSSI, measurement 
of lesion size, vital signs) 
o Laboratory blood draw to monitor for drug-associate toxicity (CBC, CMP) 
o Patient satisfaction measures 
 
- 
Day 14 – via telephone 
o Self-reported healthcare utilization 
o Clinical characteristics (signs/symptoms associated with ABSSSI) 
o Patient satisfaction measures 
 
- 
Day 28 – via telephone  
o Self-reported healthcare utilization 
o Clinical characteristics (signs/symptoms associated with ABSSSI) 
o Patient satisfaction & quality of life measures 
 
E3 Safety and Adverse Events  
 
3.a 
Safety and Compliance Monitoring 
Antibiotic-related safety and adverse events will be captured on Day 1 in the BJH ED and at in-
person follow-up between Day 3 to Day 7 at BJH or in the Infectious Disease Clinic/ID-CRU 
through patient interview and laboratory testing.  Additional assessment will occur by patient 
interview only on Day 14 and Day 28 via telephone.  Potential safety and adverse events include: 
- 
Anaphylaxis 
- 
Infusion-related reaction (e.g., flushing, hypotension, redman’s syndrome) 
- 
Milder allergic reaction (e.g., rash) 
- 
Drug side effects (e.g., headache, rash, nausea, vomiting, diarrhea)   
- 
Nephrotoxicity 
- 
Hepatotoxicity 


 
 
 
 
 
 
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3.b 
Medical Monitoring  
i 
Investigator only 
Safety and adverse events will be monitored regularly and tallied after every 10 patients.  If 5 or 
more events are identified in the alternative treatment strategy arm employing single-dose 
dalbavancin, an Institutional Data and Safety Monitoring Board will be convened. 
ii 
Institutional Data and Safety Monitoring Board 
We have identified 3 independent experts within the Division of Infectious Diseases not involved 
with the study to form the Institutional Data Safety Monitoring Board for this study.  They will 
be tasked with performing a formal interim analysis of safety and adverse events related to the 
alternative treatment strategy arm upon request. 
3.c 
Definitions of Adverse Events 
An adverse event is defined as any untoward medical occurrence in a study subject 
administered a medication (investigational or non-investigational).  An adverse event does not 
necessarily have a causal relationship with the treatment.  An adverse event can be any 
unfavorable and unintended sign (including an abnormal finding), symptom, or disease 
temporally associated with the use of a medication (investigational or non-investigational), 
whether or not related to that medication. (definition per International Conference on 
Harmonisation, ICH)  This includes any occurrence that is new in onsent or aggravated in 
severity or frequency from the baseline condition, or abnormal results of diagnostic procedures, 
including laboratory test abnormalities. 
 
Serious adverse event: 
A serious adverse event (SAE) based on ICH is any untoward medical occurrence that at any 
dose: 
- 
Results in death 
- 
Is life-threatening 
- 
Requires inpatient hospitalization or prolongation of existing hospitalization 
- 
Results in persistent or significant disability/incapacity 
- 
Is a congenital anomaly/birth defect 
- 
Is a suspected transmittion of any infectious agent via a medicinal product 
- 
Is medically important based on medical and scientific judgment 
 
Unlisted (unexpected) adverse event 
An adverse event is considered unlisted if the nature or severity is not consistent with the 
applicable product reference safety information (e.g., package insert). 
 
Adverse event associated with use of the drug 
An adverse event is considered associated with the use of the drug if the attribution is possible, 
probably, or very likely by the relationship definitions listed in Section 3.d.i.   
 


 
 
 
 
 
 
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13
3.d 
Classification of Events 
i 
Relationship 
Not Related 
An adverse event that is not related to the use of the drug. 
 
Doubtful 
An adverse event for which an alternative explanation is more likely, e.g., concomitant drug(s), 
concomitant disease(s), or the relationship in time suggests that a causal relationship is unlikely. 
 
Possible 
An adverse event that might be due to the use of the drug.  An alternative explanation, 
e.g., concomitant drug(s), concomitant disease(s), is inconclusive.  The relationship in time is 
reasonable; therefore, the causal relationship cannot be excluded. 
 
Probable 
An adverse event that might be due to the use of the drug.  The relationship in time is 
suggestive (e.g., confirmed by dechallenge).  An alternative explanation is less likely, e.g., 
concomitant drug(s), concomitant disease(s). 
 
Very Likely 
An adverse event that is listed as a possible adverse reaction and cannot be reasonably 
explained by an alternative explanation, e.g., concomitant drug(s), concomitant disease(s).  The 
relationship in time is very suggestive (e.g., it is confirmed by dechallenge and rechallenge). 
ii 
Severity 
An assessment of severity grade will be made using the following general categorical 
descriptors: 
 
Mild:  Awareness of symptoms that are easily tolerated, causing minimal discomfort and not 
interfering with everyday activities. 
 
Moderate:  Sufficient discomfort is present to cause interference with normal activity. 
 
Severe:  Extreme distress, causing significant impairment of functioning or incapacitation. 
Prevents normal everyday activities.  The investigator should use clinical judgment in assessing 
the severity of events not directly experienced by the subject (e.g., laboratory abnormalities). 
iii 
Expectedness 
Adverse drug events associated with dalbavancin may range anywhere from 1-10%, with 
nausesa being the most common. 
3.e 
Data Collection & Reporting Procedures for Adverse Events 
Serious adverse events, including those spontaneously reported to the research team, occuring 
within 30 days after receiving the single dose of dalbavancin or “usual care” antibiotics will be 
reported to the Prinicipal Investigator within 24 hours.  Any event requiring hospitalization (or 


 
 
 
 
 
 
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14
prolongation of hospitalization) that occurs during the course of the patient’s participation in 
the study must be reported as a SAE, except hospitalizations for the following: 
 
- 
The “usual care” arm of this study will involve hospital admission for intravenous 
antibiotic therapy.  This hospital admission for patients randomized to “usual care” 
should not be reported as an SAE. 
- 
Hospitalizations not intended to treat an acute illness or adverse event (e.g., social 
reasons such as pending placement in long-term care facility) 
- 
Surgery or procedure planned before entry into the study 
 
Data on SAEs will be collected and reported using an Adverse Event Form. 
Unlisted adverse event and any non-serious adverse event associated with the use of the drug 
will be collected and reported using an Adverse Event Form.  
 
An interim analysis of adverse events will performed after every 10 patients.  If we identify 5 or 
more adverse events possibly related to dalbavancin, we will suspend the study until we can 
have an Institutional Data and Safety Monitoring Board perform a formal interim analysis to 
determine if there is a safety issue. 
 
E4 Study Outcome Measurements and Ascertainment 
Healthcare utilization related to ABSSSI (at any time between Day 1 and Day 28): 
- 
Repeat ED visit (s) 
- 
Need for hospital admission(s) to receive intravenous antibiotics (excluding initial 
hospital admission in “usual care” arm) 
- 
Need for switch to a different oral or intravenous antibiotic to treat ABSSSI 
 
Healthcare cost related to ABSSSI management 
- 
Indirect/direct costs associated with ED visit(s) within BJC system 
- 
Indirect/direct costs associated with hospital admission(s) within BJC system 
 
Patient satisfaction & quality of life 
- 
Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) survey 
items 
- 
Rand 36-Item Health Survey 1.0 Questionnaire (SF-36) 
- 
Targeted set of questions specific to ABSSSI care and patient-centered outcomes 
 
Patient safety 
- 
Adverse drug events 
- 
Drug-associated toxicity (laboratory blood testing at Day 1 between Day 3 to Day 7) 
 
Clinical outcomes 
- 
Change in ABSSSI lesion size 
- 
Clinical resolution of symptoms 
- 
Need for additional intravenous/oral antibiotic therapy 
 


 
 
 
 
 
 
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15
F Statistical Plan  
 
F1  Sample Size Determination and Power 
As this a feasibility study and none of the existing literature has defined the effect size of long-
acting antibiotic therapy on healthcare utilization, healthcare cost, or patient satisfaction to the 
best of our knowledge, a sample size determination could not be performed.  We are also 
limited by the number doses provided by Allergan to conduct this study. 
F2  Interim Monitoring and Early Stopping 
An interim analysis of adverse events will performed after every 10 patients.  If we identify 5 or 
more adverse events possibly related to dalbavancin, we will suspend the study until we can 
have an Institutional Data and Safety Monitoring Board (consisting of 3 independent experts not 
involved in the study) perform a formal interim analysis to determine if there is a safety issue. 
F3  Analysis Plan 
 
All statistical analyses, apart from interim safety analyses described above, will occur at the end 
of study enrollment and after the final participant has completed their 28-day follow-up. 
F4  Statistical Methods  
Measures assessed in this study will include healthcare service utilization, healthcare-associated 
costs, patient satisfaction, patient safety, and clinical outcomes.  Univariate comparisons among 
categorical variables will be conducted with Chi square test or Fisher’s exact test, as 
approprirate.  Comparisons among continuous variables will be performed using student’s T-
test, Mann Whitney U test, or other tests, as appropriate.  A two-sided P value <0.05 will be 
considered statistically significant. 
 
G Data Handling and Record Keeping  
G1 Confidentiality and Security 
Patients will be approached for participation in the privacy of their ED treatment room.  Consent 
and treatment will also occur in this setting.  Demographic, clinical, patient satisfaction, and 
healthcare cost and utilization data will be collected during the study through a combination of 
electronic medical record review, patient interview in a private setting, and informatics data 
retrieval to achieve the aims of the study and not invade the rights of participants to privacy of 
their personal information.  Only the minimum necessary private patient information will be 
collected for the purposes of this study.  Interventions will occur in a private clinical care setting. 
 
All data will be stored in a secured environment.  Initial data will be collected in the BJH ED 
and/or hospital on paper forms and entered into a secure REDCap database at a later time.  A 
study number associated with participant will be listed on each data collection form.  The paper 
record will be stored in a secure file cabinet in a locked office within the Division of Emergency 
Medicine ECRC, to which only the emergency medicine research coordinators will have access 


 
 
 
 
 
 
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16
to.  Subsequent data collection using paper forms in the Infectious Diseases Clinic/ID-CRU will be 
stored in a secure file cabinet within the Division of Infectious Diseases, to which only the ID-
CRU research staff will have access to, and will also be entered into the secure REDCap database 
at a later time. 
 
Once data on paper forms have been abstracted to REDCap, study participant data will be de-
identified, eliminating name and other personal identifiers, including medical record numbers.  
The study number will serve as the only means to link study participant data in REDCap back to 
the paper records.  REDCap is a secure, password-protected electronic tool for capturing and 
storing research data, administered locally through the Washington University Institute of 
Clinical and Translational Sciences (ICTS).  
G2 Training  
All research staff associated with this study will have receive regularly formal training on HIPAA, 
ethical research conduct, and study-specific procedures and protocols. 
 
H Study Administration 
H1 Funding Source and Conflicts of Interest 
This study is funded through by a Project Award through the Foundation for Barnes-Jewish 
Hospital.  Study drug (dalbavancin) is provided without cost through an Investigator-Initiated 
Clinical Trial research grant through Allergan, the maker of dalbavancin.  Allergan will have no 
influence in the design, conduct, analysis, or publication of the study and/or its findings as part 
of a fully-executed Agreement.  We will provide quarterly and final updates to Allergan 
regarding the status of the study.  Washington University will retain rights to the study data. 
H2 Subject Stipends or Payments  
Study participants will receive a $25 gift card at the time of study enrollment on Day 1 and at in-
person follow-up between Day 3 and Day 7.  Participant social security numbers will be collected 
solely for tax purposes and stored separate from study data. 
 
I Publication Plan  
We will submit a final report of the findings of this study to the Foundation for Barnes-Jewish 
Hospital and Allergan.  It is our intent to publish study findings in a peer-reviewed medical 
journal. 
 
J References 
 
[1] Lodise TP, Fan W, Sulham KA. Hospital admission patterns in adult patients with skin and soft 
tissue infections: identification of potentially avoidable hospital admissions through a 
retrospective database analysis. Hosp Pract 2015;43(3):137-143. 


 
 
 
 
 
 
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17
[2] Marwick C, Broomhall J, McCowan C, et al. Severity assessment of skin and soft tissue 
infections: cohort study of management and outcomes for hospitalized patients. J Antimicrob 
Chemother 2011;66(2):387-397. 
[3] Boucher HW, Wilcox M, Talbot GH, et al. Once-weekly dalbvancin versus daily conventional 
therapy for skin infection. N Engl J Med 2014;370:2169-79. 
[4] Dunne MW, Puttagunta S, Giordano P, et al. A randomized clinical trial of single-dose versus 
weekly dalbavancin for treatment of acute bacterial skin and skin structure infection. Clin Infect 
Dis 2016;62:545-551. 
[5] Ektare V, Khachatryan A, Xue M, et al. Assessing the economic value of avoiding hospital 
admissions by shifting the management of Gram-positive acute bacterial skin and skin-structure 
infections to an outpatient care setting. J Med Econ 2015;18:1092-1101. 
[6] Lodise TP, Fan W, Sulham KA. Economic impact of oritavancin for the treatment of acute 
bacterial skin and skin structure infections in the emergency department or observation setting: 
cost savings associated with avoidable hospitalizations. Clin Ther 2016;38:136-148. 
[7] Jensen IS, Lodise TP, Fan W, et al. Use of oritavancin in acute bacterial skin and skin structure 
infections patients receiving intravenous antibiotics: a US hospital budget impact analysis. Clin 
Drug Investig 2016;36:157-168.