Clinical trial NCT01147640 (phase 2, status: completed)
Conditions: complicated intra-abdominal infection
ICD codes: D18.03, C83.73, C84.03, C84.13, C81.73, C81.93, C82.93
Drugs: cxa-101/ tazobactam and metronidazole, meropenem plus saline placebo
SMILES: CC1=NC=C(N1CCO)[N+]([O-])=O, CN(C)CCOC(C)(C1=CC=CC=C1)C1=CC=CC=N1
Eligibility criteria:

        Inclusion Criteria:

          -  Male or female, from 18 to 90 years of age, inclusive

          -  One of the following diagnoses (in which there is evidence of intraperitoneal
             infection) including:(a) Cholecystitis (including gangrenous cholecystitis) with
             rupture, perforation, or progression of the infection beyond the gallbladder
             wall;(b)Diverticular disease with perforation or abscess; (c) Appendiceal perforation
             or periappendiceal abscess; (d) Acute gastric or duodenal perforation, only if
             operated on >24 hours after perforation occurs; (e) Traumatic perforation of the
             intestine, only if operated on > 12 hours after perforation occurs; (f) Peritonitis
             due to perforated viscus, postoperative or spread from other focus of infection (but
             not spontaneous [primary] bacterial peritonitis or peritonitis associated with
             cirrhosis and chronic ascites).Subjects with inflammatory bowel disease or ischemic
             bowel disease are eligible provided there is bowel perforation; or (g) Intraabdominal
             abscess (including liver and spleen).

          -  Subject requires surgical intervention (e.g. laparotomy, laparoscopic surgery, or
             percutaneous draining of an abscess) within 24 hours of (before or after) the first
             dose of study drug

          -  If subject is to be enrolled preoperatively, the subject must have radiographic
             evidence of bowel perforation or intraabdominal abscess

          -  Subjects who failed prior antibacterial treatment for the current cIAI can be enrolled
             but must: (a) have a positive culture (from an intraabdominal site) and (b) require
             surgical intervention. Such subjects can be enrolled before the results of the culture
             are known; however, if the culture is negative, study drug administration must be
             discontinued.

          -  Willing and able to comply with all study procedures and restrictions

          -  Willing and able to provide written informed consent

        Exclusion Criteria:

          -  Women who are pregnant, nursing, or - if of child bearing potential - not using a
             medically accepted, effective method of birth control (e.g. condom, oral
             contraceptive, indwelling intrauterine device, or sexual abstinence)

          -  Diagnosis of abdominal wall abscess; small bowel obstruction or ischemic bowel disease
             without perforation; traumatic bowel perforation with surgery within 12 hours;
             perforation of gastroduodenal ulcer with surgery within 24 hours (these are considered
             situations of peritoneal soiling before infection has become established); another
             intraabdominal process in which the primary etiology is not likely to be infectious.

          -  Simple cholecystitis, gangrenous cholecystitis without rupture, simple appendicitis,
             acute suppurative cholangitis, infected, necrotizing pancreatitis, or pancreatic
             abscess

          -  cIAI managed by staged abdominal repair (STAR), open abdomen technique or any
             situation where infection source control is not likely to be achieved

          -  Known prior to randomization to have an IAI or postoperative infection caused by
             pathogen(s) resistant to meropenem

          -  Considered unlikely to survive the 4- to 5-week study period

          -  Any rapidly-progressing disease or immediately life-threatening illness (including
             acute hepatic failure, respiratory failure and septic shock)

          -  The need for concomitant systemic antibacterial agents (other than vancomycin or
             linezolid) in addition to study drug(s)

          -  Moderate or severe impairment of renal function (estimated CrCl < 50 mL/min), or
             requirement for peritoneal dialysis, hemodialysis or hemofiltration, or oliguria (< 20
             mL/h urine output over 24 hours)

          -  The presence of hepatic disease defined as: (a) ALT or AST > 4 x ULN; (b)Total
             bilirubin >2 x ULN, unrelated to cholecystitis (c) Alkaline phosphatase >4 x ULN.
             Subjects with a value >4 x ULN and <5 x ULN are eligible if this value is historically
             stable.

          -  Subjects with acute hepatic failure or acute decompensation of chronic hepatic failure

          -  Hematocrit < 25% or hemoglobin < 8 gm/dL

          -  Neutropenia with absolute neutrophil count < 1000/mm3

          -  Platelet count < 75,000 /mm3. Subjects with a platelet count as low as 50,000 /mm3 are
             permitted if the reduction is historically stable.

          -  Immunocompromising illness, including known human immunodeficiency virus (HIV)
             positivity or AIDS, organ (including bone marrow) transplant recipients, and
             hematological malignancy. Immunosuppressive therapy, including use of high-dose
             corticosteroid therapy (e.g. >40 mg prednisone or equivalent per day for greater than
             2 weeks).

          -  History of hypersensitivity reactions to cephalosporins, carbapenems, penicillins,
             ß-lactamase inhibitors, metronidazole, or nitroimidazole derivatives. Subjects with a
             history of mild skin rash, not documented to be caused by previous ß-lactam use, may
             be enrolled.

          -  Any condition or circumstance that, in the opinion of the Investigator, would
             compromise the safety of the subject or the quality of study data

          -  Clinically significant abnormality in baseline electrocardiogram (ECG)

          -  Participation in any investigational drug or device study within 30 days prior to
             study entry

          -  Use of systemic antibiotic therapy for IAI for 24 or more hours in the 48-hour period
             prior to the first dose of study drug, unless there is a documented treatment failure
             with such therapy

          -  More than one dose of an active non-study antibacterial regimen was given
             postoperatively. For subjects enrolled preoperatively, no postoperative non-study
             antibacterial therapy is allowed

          -  who previously participated in a study with CXA-101

          -  Subjects who previously received imipenem, meropenem, doripenem or cefepime for the
             current intraabdominal infection

          -  Subjects who have received disulfiram in the past 14 days or who are currently
             receiving probenecid.