SIS Multicenter Study of Duration of Antibiotics for Intraabdominal Infection

Sponsor

University of Virginia (Other)

Overall Status

Completed

CT.gov ID

NCT00657566

Collaborator

National Institute of General Medical Sciences (NIGMS) (NIH)

518

Enrollment

Locations

Arms

Duration (Months)

22.5

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Peritonitis	Other: duration of antibiotics Other: duration of antibiotics	Phase 3

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 Design

Study Type:

Interventional

Actual Enrollment :

518 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

SIS Multicenter Study of Duration of Antibiotics for Intraabdominal Infection

Study Start Date :

Sep 1, 2008

Actual Primary Completion Date :

Aug 1, 2013

Actual Study Completion Date :

Aug 1, 2014

Arms and Interventions

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 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

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

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

Outcome Measures

Primary Outcome Measures

The primary endpoint will be percentage failure conditioned by assigned duration of antibiotic therapy (intent to treat analysis). [30 days]

Secondary Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

16 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Maricopa Medical Center-Phoenix	Phoenix	Arizona	United States	85008
2	University of California Davis	Sacramento	California	United States
3	University of California San Diego	San Diego	California	United States
4	University of California San Francisco	San Francisco	California	United States
5	University of Miami	Miami	Florida	United States	33136
6	Univestity of Kansas	Kansas City	Kansas	United States
7	Louisville-VA	Louisville	Kentucky	United States	40121
8	Louisville-University Hospital	Louisville	Kentucky	United States	40202
9	Johns Hopkins	Baltimore	Maryland	United States	21205
10	Brigham and Womens	Boston	Massachusetts	United States	02115
11	Univeristy of Michigan	Ann Arbor	Michigan	United States	48502
12	Washington Universtiy	Saint Louis	Missouri	United States	63110
13	Wake Forest University	Winston-Salem	North Carolina	United States
14	Case Western	Cleveland	Ohio	United States	44106
15	Ohio State University	Columbus	Ohio	United States
16	Pittsburgh VA	Pittsburgh	Pennsylvania	United States	15206
17	University of South Carolina	Columbia	South Carolina	United States
18	Universtiy of Texas San Antonio	San Antonio	Texas	United States	78229
19	University of Virginia	Charlottesville	Virginia	United States	22903
20	Medical College of Virginia-Virginia Commonwealth University Hospital	Richmond	Virginia	United States	23298
21	University of Washington-Harborview	Seattle	Washington	United States	98104
22	University of Washington - University Hospital	Seattle	Washington	United States	98195
23	St Michael's	Toronto	Ontario	Canada