Clinical trial NCT00657566: SIS Multicenter Study of Duration of Antibiotics for Intraabdominal Infection
Official title: SIS Multicenter Study of Duration of Antibiotics for Intraabdominal Infection
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Peritonitis
Keywords: intraabdominal
peritonitis
sepsis
duration
antibiotics
Lead sponsor: University of Virginia
Sponsor class: OTHER
Collaborators: name: National Institute of General Medical Sciences (NIGMS)
First posted: 2008-04-14
Enrollment: 518
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The major hypothesis to be tested is that the treatment of intraabdominal infections that have been adequately treated operatively or by percutaneous techniques with three to five days of antibiotics will result in outcomes equivalent to the current standard where treatment is carried out until the patient has returned to normal (normal white blood cell count, temperature, and intestinal function), and that patients treated for three to five days will receive fewer days of antibiotics than the control group that has traditionally received seven to 14 days of treatment.

Detailed description: Overall, this is a prospective, randomized, single-blinded (analysis), fifteen-center study using intent to treat analysis. Patients will be identified and after informed consent is obtained, will be randomized to receive antibiotics for 3 to 5 days (4 ± 1 days) after the initial surgical or percutaneous intervention or antibiotics until two calendar days after the patient's white blood cell count, systemic temperature, and gastrointestinal function have normalized (maximum of 10 days). The primary endpoint is the composite rate of in-hospital death and/or recurrence of intraabdominal infection and/or occurrence of surgical site (wound) infection. Secondary endpoints include the occurrence of any infection at any site and infection with antibiotic-resistant pathogens. Patient data through the thirty days following the initial intervention or until hospital discharge (whichever is longer) will be tracked

Eligibility criteria: Inclusion Criteria:

* age ≥ 16 at some sites,(≥ 18 at UVA)
* ability to obtain informed consent from the subject or surrogate
* Presence of an intraabdominal infection requiring any duration of hospitalization and managed with open, laparoscopic, or percutaneous intervention.
* A peripheral white blood cell count of \> 11,000/mm and/or temperature ≥ 38.0 C with in 24 hours or gastrointestinal dysfunction sufficient to prevent intake of normal diet within 24hrs of initial operative or percutaneous intervention.
* Adequate source control in the opinion of the local investigator and PI. Source control is defined as any procedure that stops the ongoing contamination of the peritoneal cavity and removes the majority of the contaminated intraperitoneal contents to the extent that no further acute interventions are felt to be necessary.

Exclusion Criteria:

* age \< 16 years at some sites(\< 18 at UVA)
* Inability to obtain consent from the patient, parents, or surrogate
* Lack of adequate source control in the opinion of the local investigator or overall PI ( Robert Sawyer)
* High likelihood of death within 72 hours of initial intervention in the opinion of the local investigator or principal investigator
* Lack of any clinical improvement within 72 hours of initial intervention in the opinion of the local investigator or principal investigator.
* Planned relaparotomy
* Perforated gastric ulcer or duodenal ulcer treated within 24hours of the onset of symptoms
* Traumatic injury to the bowel (including iatrogenic or intra-operative) treated within 12 hours of injury
* Non-perforated, non-gangrenous appendicitis or cholecystitis
* Gangrenous appendicitis or peritonitis without confirmatory cultures or with cultures without bacterial or fungal growth
* Ischemic or necrotic intestine without perforation and without positive bacterial or fungal cultures
* Intraabdominal infection associated with active necrotizing pancreatitis
* Primary (spontaneous) bacterial peritonitis
* Intraabdominal infection associated with an indwelling continuous ambulatory peritoneal dialysis catheter.
* Primary skin closure of an open surgical incision in the presence of diffuse, non-localized peritonitis. Laparoscopic port sites ≥ 2cm may be closed
* Pregnancy
* Prior enrollment in this study
* Enrollment in another therapeutic trial

Primary outcomes:
measure: The primary endpoint will be percentage failure conditioned by assigned duration of antibiotic therapy (intent to treat analysis).
timeFrame: 30 days
Secondary outcomes:
measure: Failure rate for clinically evaluable patients receiving the appropriate duration of antibiotics
timeFrame: 30 days
measure: failure rate for microbiologically evaluable patients
timeFrame: 30 days
measure: rate of need for reintervention in the abdomen
timeFrame: 30 days
measure: rate of surgical site infection
timeFrame: 30 days
measure: rate of death within 30 days
timeFrame: 30 days
measure: duration of hospitalization
timeFrame: 30 days
measure: rate of intraabdominal or surgical site failure due to antimicrobial-resistant pathogens
timeFrame: 30 days
measure: rate of any subsequent infection at a site other than the abdomen or the surgical site
timeFrame: 30 days
measure: rate of infection at a non-abdominal, non-surgical site with a resistant organism
timeFrame: 30 days
measure: rate of Clostridium difficile infection
timeFrame: 30 days
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Maricopa Medical Center-Phoenix
state: Arizona
city: Sacramento
country: United States
facility: University of California Davis
state: California
city: San Diego
country: United States
facility: University of California San Diego
state: California
city: San Francisco
country: United States
facility: University of California San Francisco
state: California
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Kansas City
country: United States
facility: Univestity of Kansas
state: Kansas
city: Louisville
country: United States
facility: Louisville-VA
state: Kentucky
city: Louisville
country: United States
facility: Louisville-University Hospital
state: Kentucky
city: Baltimore
country: United States
facility: Johns Hopkins
state: Maryland
city: Boston
country: United States
facility: Brigham and Womens
state: Massachusetts
city: Ann Arbor
country: United States
facility: Univeristy of Michigan
state: Michigan
city: Saint Louis
country: United States
facility: Washington Universtiy
state: Missouri
city: Winston-Salem
country: United States
facility: Wake Forest University
state: North Carolina
city: Cleveland
country: United States
facility: Case Western
state: Ohio
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
city: Pittsburgh
country: United States
facility: Pittsburgh VA
state: Pennsylvania
city: Columbia
country: United States
facility: University of South Carolina
state: South Carolina
city: San Antonio
country: United States
facility: Universtiy of Texas San Antonio
state: Texas
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
city: Richmond
country: United States
facility: Medical College of Virginia-Virginia Commonwealth University Hospital
state: Virginia
city: Seattle
country: United States
facility: University of Washington-Harborview
state: Washington
city: Seattle
country: United States
facility: University of Washington - University Hospital
state: Washington
city: Toronto
country: Canada
facility: St Michael's
state: Ontario
Study officials:
affiliation: University of Virginia
name: Robert G Sawyer, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Hedrick TL, Evans HL, Smith RL, McElearney ST, Schulman AS, Chong TW, Pruett TL, Sawyer RG. Can we define the ideal duration of antibiotic therapy? Surg Infect (Larchmt). 2006 Oct;7(5):419-32. doi: 10.1089/sur.2006.7.419.
citation: Sawyer RG, Claridge JA, Nathens AB, Rotstein OD, Duane TM, Evans HL, Cook CH, O'Neill PJ, Mazuski JE, Askari R, Wilson MA, Napolitano LM, Namias N, Miller PR, Dellinger EP, Watson CM, Coimbra R, Dent DL, Lowry SF, Cocanour CS, West MA, Banton KL, Cheadle WG, Lipsett PA, Guidry CA, Popovsky K; STOP-IT Trial Investigators. Trial of short-course antimicrobial therapy for intraabdominal infection. N Engl J Med. 2015 May 21;372(21):1996-2005. doi: 10.1056/NEJMoa1411162.