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Study Comparing the Safety and Efficacy of Intravenous CXA-201 and Intravenous Meropenem in Complicated Intraabdominal Infections

Phase 3
Completed
Conditions
Complicated Intra-abdominal Infection
Interventions
Registration Number
NCT01445678
Lead Sponsor
Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
Brief Summary

This is a Phase 3, multicenter, prospective, randomized, double-blind, double dummy study of CXA-201 Intravenous (IV) infusions (1500mg q8h) and metronidazole (500mg q8h) versus meropenem (1000mg q8h)for the treatment of adults with Complicated Intraabdominal Infections (cIAI).

Detailed Description

Approximately, 500 subjects will be enrolled into this study, randomized 1:1 to receive CXA-201 and metronidazole or comparator (meropenem). Subject participation will require a minimum commitment of 38 days and a maximum of 45 days. An End of Treatment (EOT) visit will occur within 24 hours following the last dose of study drug administration/drug discontinuation. A Test of Cure (TOC)/Safety visit will be conducted 26 to 30 days following the first dose of study drug administration. A Last Follow-up (LFU) visit will be conducted 38 to 45 days after the first dose of study drug.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
494
Inclusion Criteria
  • Diagnoses of cIAI.
  • 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.
Exclusion Criteria
  • Simple appendicitis; acute suppurative cholangitis; infected necrotizing pancreatitis; pancreatic abscess; or pelvic infections.
  • Complicated intraabdominal infection managed by staged abdominal repair (STAR), open abdomen technique including temporary closure of the abdomen, or any situation where infection source control is not likely to be achieved.
  • Use of systemic antibiotic therapy for IAI for more than 24 hours prior to the first dose of study drug, unless there is a documented treatment failure with such therapy.
  • Have a concomitant infection at the time of randomization, which requires non-study systemic antibacterial therapy in addition to IV study drug therapy. (Drugs with only gram-positive activity [e.g., daptomycin, vancomycin, linezolid] are allowed).
  • Severe impairment of renal function (estimated CrCl < 30 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 at baseline.
  • Considered unlikely to survive the 4 to 5 week study period.
  • Any rapidly-progressing disease or immediately life-threatening illness (including respiratory failure and septic shock).
  • Have a documented history of any moderate or severe hypersensitivity or allergic reaction to any β-lactam antibacterial (a history of a mild rash followed by uneventful re-exposure is not a contraindication to enrollment), including cephalosporins, carbapenems, penicillins, or ß-lactamase inhibitors, or metronidazole, or nitroimidazole derivatives.
  • Women who are pregnant or nursing.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
CXA-201 and Metronidazole as treatment for cIAICXA-201 and metronidazole-
Meropenem as treatment for cIAIMeropenem-
Primary Outcome Measures
NameTimeMethod
The Percentage of Subjects With Clinical Outcome of Cure at the Test of Cure (TOC) Visit in the Microbiological Intent to Treat (MITT) PopulationTOC; 26-30 days after start of study drug administration

Clinical cure is complete resolution or significant improvement in 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
NameTimeMethod
The Percentage of Subjects With Clinical Response at End of Therapy (EOT) Visit in the MITT PopulationEOT; Within 24 hours of last study drug administration

Clinical response is complete resolution or significant improvement in signs and symptoms of the index infection, such that no additional antibacterial therapy or surgical or drainage procedure was required for the index infection.

The Percentage of Subjects With Microbiological Outcome of Success at the TOC Visit in the Microbiologically Evaluable (ME) PopulationTOC; 26-30 days after start of study drug administration

Success is eradication (absence of the baseline pathogen in a specimen appropriately obtained from the original site of infection) or presumed eradication (absence of material to culture in a subject who was assessed as a clinical cure) for each baseline pathogen

The Percentage of Subjects With Clinical Response at Long Term Follow-Up (LFU) in the MITT PopulationLFU; 38 to 45 days after first study drug administration

Clinical response is clinical cure at TOC and no signs and symptoms recur or worsen since the TOC visit.

The Percentage of Subjects With Clinical Response at End of Therapy in the ME PopulationEOT; Within 24 hours of last study drug administration

Clinical response is complete resolution or significant improvement in signs and symptoms of the index infection, such that no additional antibacterial therapy or surgical or drainage procedure was required for the index infection.

The Percentage of Subjects With Clinical Response at LFU Visit in the ME PopulationLFU; 38 to 45 days after first study drug administration

Clinical response is clinical cure at TOC and no signs and symptoms recur or worsen since the TOC visit

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