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Safety and Efficacy Study to Compare IV CXA 101/Tazobactam and Metronidazole With Meropenem in Complicated Intraabdominal Infections

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01147640
First Posted: June 22, 2010
Last Update Posted: January 8, 2016
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Cubist Pharmaceuticals LLC
  Purpose
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 matching saline placebo (q8h) in the treatment of cIAI in adult subjects. Dose adjustments for subjects with mild renal impairment are not necessary and subjects with more severe degrees of renal failure are excluded.

Condition Intervention Phase
Complicated Intra-abdominal Infection Drug: CXA-101/ tazobactam and metronidazole Drug: meropenem plus saline placebo Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Multicenter, Double-Blind, Randomized, Phase 2 Study to Compare the Safety and Efficacy of Intravenous CXA 101/ Tazobactam and Metronidazole With That of Meropenem in Complicated Intraabdominal Infections

Resource links provided by NLM:


Further study details as provided by Cubist Pharmaceuticals LLC:

Primary Outcome Measures:
  • Clinical Response of CXA 101/Tazobactam and Metronidazole at Test of Cure (TOC) Visit in the Microbiological Modified Intent to Treat (mMITT) Analysis Population [ Time Frame: Test-of-Cure Visit (7-14 days after End of Therapy [EOT]) ]
    Clinical response is complete resolution or significant improvement of all signs and symptoms of the index infection, such that no additional antibacterial therapy or surgical or drainage procedure was required for the index infection.


Secondary Outcome Measures:
  • Microbiological Response of CXA 101/Tazobactam and Metronidazole at the TOC Visit in the Microbiologically Evaluable (ME) Population [ Time Frame: Test-of-Cure Visit (7-14 days after EOT) ]
    Microbiological response is eradication (absence of the baseline pathogen from a suitable intra-abdominal specimen) or presumed eradication (absence of a suitable intra-abdominal specimen to culture at the TOC visit in a subject who is assessed as a clinical cure at TOC)


Enrollment: 122
Study Start Date: June 2010
Study Completion Date: March 2011
Primary Completion Date: February 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: CXA 101/tazobactam and metronidazole Drug: CXA-101/ tazobactam and metronidazole
CXA-101/tazobactam (1000/500 mg q8h) plus metronidazole (500 mg q8h) administered via IV infusion
Active Comparator: meropenem with matching saline placebo Drug: meropenem plus saline placebo
meropenem IV infusion (1000 mg q8h) plus a matching saline placebo (q8h) administered via IV infusion

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 90 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01147640


  Show 33 Study Locations
Sponsors and Collaborators
Cubist Pharmaceuticals LLC
Investigators
Study Director: Ian Friedland, MD Cubist Pharmaceuticals LLC
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Cubist Pharmaceuticals LLC
ClinicalTrials.gov Identifier: NCT01147640     History of Changes
Other Study ID Numbers: 7625A-012
CXA-IAI-10-01 ( Other Identifier: Cubist Study Number )
First Submitted: June 17, 2010
First Posted: June 22, 2010
Results First Submitted: January 9, 2015
Results First Posted: January 16, 2015
Last Update Posted: January 8, 2016
Last Verified: January 2016

Additional relevant MeSH terms:
Infection
Communicable Diseases
Intraabdominal Infections
Meropenem
Tazobactam
Metronidazole
Thienamycins
Penicillanic Acid
Cephalosporins
Anti-Infective Agents
Antiprotozoal Agents
Antiparasitic Agents
Anti-Bacterial Agents
beta-Lactamase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action