SIS Multicenter Study of Duration of Antibiotics for Intraabdominal Infection

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.

Study Overview

• Status: Completed
• Conditions: Peritonitis
• Intervention / Treatment: Other: duration of antibiotics; Other: duration of antibiotics

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

• Study Type: Interventional
• Enrollment (Actual): 518
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada
      • St Michael's
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85008
      • Maricopa Medical Center-Phoenix
  • California
    • Sacramento, California, United States
      • University of California Davis
    • San Diego, California, United States
      • University of California San Diego
    • San Francisco, California, United States
      • University of California San Francisco
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami
  • Kansas
    • Kansas City, Kansas, United States
      • Univestity of Kansas
  • Kentucky
    • Louisville, Kentucky, United States, 40121
      • Louisville-VA
    • Louisville, Kentucky, United States, 40202
      • Louisville-University Hospital
  • Maryland
    • Baltimore, Maryland, United States, 21205
      • Johns Hopkins
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Womens
  • Michigan
    • Ann Arbor, Michigan, United States, 48502
      • Univeristy of Michigan
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington Universtiy
  • North Carolina
    • Winston-Salem, North Carolina, United States
      • Wake Forest University
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • Case Western
    • Columbus, Ohio, United States
      • Ohio State University
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15206
      • Pittsburgh VA
  • South Carolina
    • Columbia, South Carolina, United States
      • University of South Carolina
  • Texas
    • San Antonio, Texas, United States, 78229
      • Universtiy of Texas San Antonio
  • Virginia
    • Charlottesville, Virginia, United States, 22903
      • University of Virginia
    • Richmond, Virginia, United States, 23298
      • Medical College of Virginia-Virginia Commonwealth University Hospital
  • Washington
    • Seattle, Washington, United States, 98104
      • University of Washington-Harborview
    • Seattle, Washington, United States, 98195
      • University of Washington - University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 1; antibiotics received for up to two days following normalization of white blood cell count, temperature, and gastrointestinal function	Other: duration of antibiotics; 4 +/- 1 days of antibiotics; Other Names: short course; Other: duration of antibiotics; active comparator antibiotics given until 2 days after resolution of fever, elevated white blood cell count, and gastrointestinal dysfunction.; Other Names: long course
Experimental: 2; 4 +/- 1 days of antibiotics	Other: duration of antibiotics; 4 +/- 1 days of antibiotics; Other Names: short course; Other: duration of antibiotics; active comparator antibiotics given until 2 days after resolution of fever, elevated white blood cell count, and gastrointestinal dysfunction.; Other Names: long course

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The primary endpoint will be percentage failure conditioned by assigned duration of antibiotic therapy (intent to treat analysis).	30 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Failure rate for clinically evaluable patients receiving the appropriate duration of antibiotics	30 days
failure rate for microbiologically evaluable patients	30 days
rate of need for reintervention in the abdomen	30 days
rate of surgical site infection	30 days
rate of death within 30 days	30 days
duration of hospitalization	30 days
rate of intraabdominal or surgical site failure due to antimicrobial-resistant pathogens	30 days
rate of any subsequent infection at a site other than the abdomen or the surgical site	30 days
rate of infection at a non-abdominal, non-surgical site with a resistant organism	30 days
rate of Clostridium difficile infection	30 days

Collaborators and Investigators

• Sponsor: University of Virginia
• Collaborators: National Institute of General Medical Sciences (NIGMS)
• Investigators: Principal Investigator: Robert G Sawyer, MD, University of Virginia

Publications and helpful links

General Publications

• 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.
• 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. Erratum In: N Engl J Med. 2018 Jan 25;:null.

Study record dates

Study Major Dates

• Study Start: September 1, 2008
• Primary Completion (Actual): August 1, 2013
• Study Completion (Actual): August 1, 2014

Study Registration Dates

• First Submitted: April 10, 2008
• First Submitted That Met QC Criteria: April 10, 2008
• First Posted (Estimate): April 14, 2008

Study Record Updates

• Last Update Posted (Actual): May 22, 2018
• Last Update Submitted That Met QC Criteria: May 18, 2018
• Last Verified: May 1, 2018

More Information

Terms related to this study

• Keywords: peritonitis; sepsis; antibiotics; duration; intraabdominal
• Additional Relevant MeSH Terms: Digestive System Diseases; Infections; Peritoneal Diseases; Intraabdominal Infections; Peritonitis; Anti-Infective Agents; Antitubercular Agents; Anti-Bacterial Agents; Antibiotics, Antitubercular
• Other Study ID Numbers: 13447 (Other Identifier: City of Hope Medical Center); 1R01GM081510-01 (U.S. NIH Grant/Contract)