Clinical trial NCT06002607: Shorter Versus Extended Course of Antibiotic Therapy for Necrotizing Soft Tissue Infections
Official title: Pilot Randomized Controlled Trial of Shorter Versus Extended Course of Antibiotic Therapy for Necrotizing Soft Tissue Infections
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Necrotizing Soft Tissue Infection
Lead sponsor: University of California, Irvine
Sponsor class: OTHER
First posted: 2023-08-21
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Adult patients with a diagnosis of Necortizing Soft Tissue Infection who undergo consultation by the Emergency General Surgery service.

Brief summary: Necrotizing soft tissue infection (NSTI) is a devastating disease that results in a high rate of in-hospital complications and despite advances in critical care, wound care, and early intervention, NSTI continues to be associated with a mortality rate of nearly 30%. The antibiotics used in this treatment are Clindamycin, Vancomycin, Piperacillin Tazobactam; these antibiotics may be administered combined or individually, based on individualized patient treatment. Although one of the tenets of management for NSTI is early broad-spectrum intravenous antibiotics (listed above), the duration of antibiotics needed is not well defined. Currently, there exists wide variation in the duration of antibiotics for NSTI ranging between 2-16 days. The objective of this study is to evaluate the safety of a shorter course of antibiotics hypothesizing that a short duration of antibiotics for 48-hours after source-control is achieved will have similar risk of morbidity and mortality compared to a 7-day course of antibiotics post source control. A second aim of this study will be to identify if serum procalcitonin levels/ratio correspond to resolution of systemic infection in patients with NSTI.

Detailed description: The objective of this study is to evaluate the safety of a shorter course of antibiotics hypothesizing that a short duration of antibiotics for 48-hours after source-control is achieved will have similar risk of morbidity and mortality compared to a 7-day course of antibiotics post source control. The proposed shortened duration is considered within standard of care as the IDSA suggests 48-72 hours of antibiotics after source control, however this was due mostly to expert opinion until a recent single-center study using historical controls demonstrated a 48-hour duration of antibiotics to be safe. A second aim of this study will be to identify if serum procalcitonin levels/ratio correspond to resolution of systemic infection in patients with NSTI. This pilot study may help limit use of antibiotics which are associated with both cost and significant adverse events including antimicrobial resistance and clostridium difficile infections. In addition, the data would support grant submission of a larger, multi-center study with sufficient power to demonstrate the safety profile and potential benefits of a shorter duration of antibiotics, which has been shown to be beneficial in previous large surgical infection studies.

Specific Aims:

Aim#1: Establish the safety of an abbreviated course (48 hours after source control) compared to a prolonged (7 days after source control) course of antibiotics in terms of in-hospital mortality.

Aim#2: Compare the incidence of hospital length of stay and in-hospital complications including unplanned return to the operating room, ventilator days, and antibiotic associated complications (e.g., clostridium difficile infection) in the two comparison groups: abbreviated (48-hours) and prolonged antibiotics (7-days) after source control.

Aim#3: Identify a critical threshold of biochemical procalcitonin or a % decrease in procalcitonin from the initial procalcitonin obtained upon admission that suggests resolution of systemic infection in patients with NSTI. This will be done by obtaining a serum procalcitonin upon admission and daily for up to 7 days from admission or once source control has been achieved.

Eligibility criteria: Inclusion Criteria:

* Adult patients 18 years of age or older with all following criteria:
* Presenting to the Emergency Department with history, exam and/or imaging concerning NSTI, AND
* Patients who undergo consultation by the Emergency General Surgery service, AND
* Patients included must have skin or soft tissue findings consistent with NSTI (erythema, crepitus, or pain out of proportion to exam), AND
* Systemic signs of infection including fever (temperature \>38.0°C) or leukocytosis (≥11,000 peripheral white cells per cubic millimeter), AND
* Patients who undergo excisional debridement and/or amputation to achieve source control.

Exclusion Criteria:

* Pregnant patients
* Prisoners
* Patients with bacteremia upon admission
* Patients unable to provide consent (including no legally authorized representative)

Primary outcomes:
measure: Safety of the antibiotic course duration
timeFrame: Through study completion, an average of 1 year
measure: Mortality rate
timeFrame: Through study completion, an average of 1 year
Secondary outcomes:
measure: Age
timeFrame: Baseline, pre-intervention/procedure/surgery
measure: Sex
timeFrame: Baseline, pre-intervention/procedure/surgery
measure: BMI (body mass index)
timeFrame: Baseline, pre-intervention/procedure/surgery
measure: Blood Pressure
timeFrame: Baseline, pre-intervention/procedure/surgery
measure: Heart Rate
timeFrame: Baseline, pre-intervention/procedure/surgery
measure: Respiratory rate
timeFrame: Baseline, pre-intervention/procedure/surgery
measure: Temperature
timeFrame: Baseline, pre-intervention/procedure/surgery
measure: Comorbidities
timeFrame: Baseline, pre-intervention/procedure/surgery
measure: Transfusion requirements
timeFrame: Baseline, pre-intervention/procedure/surgery
measure: NSTI location
timeFrame: Baseline, pre-intervention/procedure/surgery
measure: Operations
timeFrame: Through study completion, an average of 1 year
measure: Serum concentration of procalcitonin
timeFrame: Upon admission and daily blood sample for 7 days
measure: Serum concentration of white blood cell
timeFrame: Through study completion, an average of 1 year
measure: Serum concentration of hemoglobin
timeFrame: Through study completion, an average of 1 year
measure: Serum concentration of sodium
timeFrame: Through study completion, an average of 1 year
measure: Serum concentration of C-reactive protein
timeFrame: Through study completion, an average of 1 year
measure: Serum concentration of glucose
timeFrame: Through study completion, an average of 1 year
measure: Serum concentration of creatinine
timeFrame: Through study completion, an average of 1 year
measure: Total hospital length of stay
timeFrame: Through study completion, an average of 1 year
measure: Total intensive care unit (ICU)
timeFrame: Through study completion, an average of 1 year
measure: Total ventilator days
timeFrame: Through study completion, an average of 1 year
Other outcomes:
Locations:
city: Orange
country: United States
facility: University of California Irvine Medical Center
state: California
Study officials:
affiliation: University of California, Irvine
name: Areg Grigorian, MD
role: PRINCIPAL_INVESTIGATOR
References:
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