Status:
COMPLETED
Safety and Efficacy Study to Compare IV CXA 101/Tazobactam and Metronidazole With Meropenem in Complicated Intraabdominal Infections
Lead Sponsor:
Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
Conditions:
Complicated Intra-abdominal Infection
Eligibility:
All Genders
18-90 years
Phase:
PHASE2
Brief Summary
A Phase 2, multicenter, prospective, randomized, double-blind study of CXA-101/ tazobactam (1000/500 mg q8h) and metronidazole (500 mg q8h) IV infusion vs. meropenem IV infusion (1000 mg q8h) and a ma...
Eligibility Criteria
Inclusion
- 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
- 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.
Key Trial Info
Start Date :
June 25 2010
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
March 25 2011
Estimated Enrollment :
122 Patients enrolled
Trial Details
Trial ID
NCT01147640
Start Date
June 25 2010
End Date
March 25 2011
Last Update
October 25 2018
Active Locations (33)
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1
Pulmonary Consultants and Primary Care Physicians Medical Group, Inc.
Orange, California, United States, 92868
2
Los Angeles Biomedical Research Institue at Harbor UCLA Medical Center
Torrance, California, United States, 90509
3
University of Colorado Hospital
Aurora, Colorado, United States, 88045
4
Christiana Care Health System
Newark, Delaware, United States, 19718