Prospective Multicenter Doubleblind Randomized Study of NXL104/Ceftazidime + Metronidazole vs. Meropenem in Treatment of Complicated Intra-abdominal Infections

Study Overview
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Brief Summary
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The purpose of this study is to determine whether NXL104 plus ceftazidime is effective in the treatment of complicated intra-abdominal infections as compared to a comparator group.

Official Title
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A Prospective, Multicenter, Double-blind, Randomized, Comparative Study to Estimate the Safety, Tolerability and Efficacy of NXL104/Ceftazidime Plus Metronidazole vs. Meropenem in the Treatment of Complicated Intra-abdominal Infections in Hospitalized Adults

Conditions
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Complicated Intra-abdominal Infections

Intervention / Treatment
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* Drug: ceftazidime/NXL104 + metronidazole
* Drug: meropenem


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: complicated intra-abdominal infections Exclusion Criteria: infections limited to hollow viscus ischemic bowel disease without perforation acute suppurative cholangitis acute necrotizing pancreatitis pts to undergo stated abdominal repair, open abdomen technique or marsupialization Apache II >25

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NXL104/CAZ/MTZ<br>NXL104/ceftazidime + metronidazole | Drug: ceftazidime/NXL104 + metronidazole<br>* IV TID<br>|
| Active Comparator: Meropenem<br> | Drug: meropenem<br>* IV TID<br>* Other names: merrem;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Clinical Response at the Test of Cure (TOC) Visit | Clinical response was defined as complete resolution or significant improvement of signs and symptoms of the index infection. No further antimicrobial therapy or surgical or radiological intervention was required. This clinical response was measured in participants who were microbiologically evaluable (ME) at baseline. | Test of cure visit: 2 weeks post-therapy (Day 28) | 
| Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 6 weeks after last dose of study treatment that were absent before treatment or that worsened relative to pretreatment state. | Baseline up to 6 weeks after last dose of study treatment (up to a maximum of 8 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Clinical Response at the End of Intravenous (IV) Therapy | Clinical response was defined as complete resolution or significant improvement of signs and symptoms of the index infection. No further antimicrobial therapy or surgical or radiological intervention was required. This clinical response was measured in participants who were ME at baseline. | End of IV therapy: From Day 5 to Day 14 | 
| Number of Participants With Clinical Response at the Late Follow-up Visit | Clinical response was defined as complete resolution or significant improvement of signs and symptoms of the index infection. No further antimicrobial therapy or surgical or radiological intervention was required. This clinical response was measured in participants who were ME at baseline. | Late follow-up visit: 4 to 6 weeks post-therapy (up to 8 weeks) | 
| Number of Participants With Microbiological Response at the Test of Cure Visit | Microbiological response was defined as eradication of pathogen identified (absence of causative pathogens from appropriately obtained specimens at site of infection) or presumptive eradication of pathogens (absence of material to culture in a participant who had responded clinically to treatment). This clinical response was measured in participants who were ME at baseline. | Test of cure visit: 2 weeks post-therapy (Day 28) | 
| Number of Participants With Microbiological Response at the End of IV Therapy | Microbiological response was defined as eradication of pathogen identified (absence of causative pathogens from appropriately obtained specimens at site of infection) or presumptive eradication of pathogens (absence of material to culture in a participant who had responded clinically to treatment). This clinical response was measured in participants who were ME at baseline. | End of IV therapy: From Day 5 to Day 14 | 
| Number of Participants With Microbiological Response at the Late Follow-up Visit | Favorable: eradication (absence of causative pathogens from appropriately obtained specimens at site of infection) or presumptive eradication (absence of material to culture in a patient who had responded clinically to treatment) | Late follow-up visit: 4 to 6 weeks post-therapy (up to 8 weeks) | 
| Number of Participants With Clinical Response in Clinically Evaluable (CE) Participants at the Test of Cure Visit | Clinical response was defined as complete resolution or significant improvement of signs and symptoms of the index infection. No further antimicrobial therapy or surgical or radiological intervention was required. | Test of cure visit: 2 weeks post-therapy (Day 28) | 
| Number of Participants With Clinical Response in CE Participants at the End of IV Therapy | Clinical response was defined as complete resolution or significant improvement of signs and symptoms of the index infection. No further antimicrobial therapy or surgical or radiological intervention was required. | End of IV therapy: From Day 5 to Day 14 | 
| Number of Participants With Clinical Response in CE Participants at the Late Follow-up Visit | Clinical response was defined as complete resolution or significant improvement of signs and symptoms of the index infection. No further antimicrobial therapy or surgical or radiological intervention was required. | Late follow-up visit: 4 to 6 weeks post-therapy (up to 8 weeks) |