Therapy of Complicated Intra-Abdominal Infections With Moxifloxacin or Ertapenem

Study Overview
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Brief Summary
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A study to compare the safety and efficacy of moxifloxacin to ertapenem in patients with intra-abdominal infections.

Official Title
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A Prospective, Randomized, Double-dummy, Double-blind, Multicenter Trial Comparing the Safety and Efficacy of Intravenous Moxifloxacin 400 mg IV QD 24 Hours to That of Ertapenem 1.0 g IV QD 24 Hours for 5 to 14 Days for the Treatment of Subjects With Complicated Intra-abdominal Infections (PROMISE Study)

Conditions
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Infection

Intervention / Treatment
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* Drug: Moxifloxacin (Avelox, BAY12-8039)
* Drug: Ertapenem intravenous


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Hospitalized men or women >/=18 years of age Expected duration of treatment with intravenous antibiotics anticipated to be >/= 5 full days but not exceeding 14 days Ability to provide documented and signed written informed consent Confirmed or suspected intra abdominal infection defined as follows: For a confirmed intra abdominal infection, a surgical procedure (laparotomy or laparoscopy) must have been performed within 24 hours prior to enrollment and reveal at least one of the following: Gross peritoneal inflammation with purulent exudates (i.e. peritonitis) Intra abdominal abscess Macroscopic intestinal perforation with localized or diffuse peritonitis Subjects enrolled on the basis of a suspected intra abdominal infection must have: Radiological evidence [abdominal plain films, computed tomography (CT), magnetic resonance imaging (MRI) or ultrasound] of gastrointestinal perforation or intra-abdominal abscess and the following signs and symptoms: Symptoms referable to the abdominal cavity (e.g. anorexia, nausea, vomiting or pain), lasting for at least 24 hours Tenderness (with or without rebound), involuntary guarding, absent or diminished bowel sounds, or abdominal wall rigidity At least two of the following SIRS criteria: Temperature > 38.0°C rectal or tympanic membrane, or temperature < 36.0°C rectal or tympanic Heart rate > 90/min Respiratory rate > 20/min WBC >12,000 cells/mm3 or < 4,000 cells/ mm3 The subject must be scheduled for a surgical procedure (laparotomy or laparoscopy) within 24 hours of enrollment of the study Exclusion Criteria: Known hypersensitivity to quinolones, and/or to carbapenems and/or to any other type of beta lactam antibiotic drugs (e.g. penicillins or cephalosporins), or any of the excipients Women who are pregnant or lactating or in whom pregnancy cannot be excluded History of tendon disease/disorder related to quinolone treatment Known congenital or documented acquired QT prolongation; uncorrected hypokalemia; clinically relevant bradycardia; clinically relevant heart failure with reduced left ventricular ejection fraction; previous history of symptomatic arrhythmias Concomitant use of any of the following drugs, reported to increase the QT interval: antiarrhythmics class IA (e.g. quinidine, hydroquinidine, disopyramide) or antiarrhythmics class III (e.g., amiodarone, sotalol, dofetilide, ibutilide), neuroleptics (e.g. phenothiazines, pimozide, sertindole, haloperidol, sultopride), tricyclic antidepressive agents, certain antimicrobials (sparfloxacin, erythromycin IV, pentamidine, antimalarials, particularly halofantrine), certain antihistaminics (terfenadine, astemizole, mizolastine), and others (cisapride, vincamine IV, bepridil, diphemanil) Known severe end stage liver disease Creatinine clearance </= 30 mL/min/1.73 m2 Systemic antibacterial therapy administered for more than 24 hours within 7 days of enrollment Need for systemic antibacterial therapy with agents other than those described in the study protocol Indwelling peritoneal catheter Pre existing ascites and presumed spontaneous bacterial peritonitis Perforation of the stomach or duodenum, if the duration of perforation is less than 24 hours or if operated on within 24 hours of perforation Perforation of the small bowel (excluding the duodenum) or large bowel, if the duration of perforation is less than 12 hours or if operated on within 12 hours of perforation All pancreatic processes including pancreatic sepsis, peri-pancreatic sepsis, or an intra abdominal infection secondary to pancreatitis Liver and splenic abscess Transmural bowel ischemia or necrosis without perforation or established peritonitis or abscess Acute and gangrenous cholecystitis without perforation Acute cholangitis Early acute, suppurative, or gangrenous non-perforated appendicitis Subjects requiring antibiotic irrigations of the abdominal cavity or surgical wound Treatment with open abdomen or marsupialization, or multiple planned re laparotomies Infections originating from the female genital tract Peri-nephric infections Evidence of sepsis with shock requiring the administration of vasopressors for more than 4 consecutive hours Known rapidly fatal underlying disease (death expected within 6 months) Neutropenia (neutrophil count < 1,000/mL) caused by immunosuppressive therapy or malignancy Receiving chronic treatment with known immunosuppressant therapy (including chronic treatment with > 15 mg/day of systemic prednisone or equivalent) Subjects known to have AIDS (CD4 count < 200/mL) or HIV seropositives who are receiving HAART (HIV positive subjects may be included. HIV testing is not required for this study protocol) Subjects with a malignant or pre malignant hematological condition, including Hodgkin's disease and non-Hodgkin lymphoma (subjects with solid tumor can be included in the study) Subjects with a Body Mass Index >/= 45 kg/m2 Previous enrollment in this study Participation in any clinical investigational drug study within the previous 4 weeks

Ages Eligible for Study
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Minimum Age: 18 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: Moxifloxacin (Avelox, BAY12-8039)<br>Subjects received placebo matching the comparator (Ertapenem dummy) and Moxifloxacin 400 mg in 250 mL for intravenous infusion every 24 hours. | Drug: Moxifloxacin (Avelox, BAY12-8039)<br>* Moxifloxacin, 400mg, administered intravenously once daily<br>|
| Active Comparator: Ertapenem<br>Subject received Ertapenem 1.0 g in 50 mL for intravenous infusion and placebo matching Moxifloxacin (Moxifloxacin dummy) every 24 hours. | Drug: Ertapenem intravenous<br>* Active treatment: Ertapenem 1.0g, administered intravenously once daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects Achieving Clinical Cure at Test of Cure (TOC) Visit in the Per Protocol Population | Clinical cure at TOC = resolution or improvement of clinical signs and symptoms related to the infection without the occurrence of a wound infection requiring a systemic antibiotic treatment. Clinical failure at TOC = either failure to respond or insufficient lessening of the signs and symptoms of infection at end of treatment (EOT) or reappearance of the signs and symptoms of the original infection from EOT up to TOC or wound infection requiring additional systemic antimicrobial therapy at any time up to TOC. | 21 to 28 days after completion of study drug therapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects Achieving Clinical Improvement During Treatment in the Per Protocol Population | Clinical improvement = Reduction in the severity and/or number of signs and symptoms of infection.Clinical failure = Failure to respond/insufficient lessening of signs and symptoms of infection requiring a modification/addition of antibacterial therapy, or a second surgical intervention (unless the original surgery was deemed inadequate). Development of a wound infection requiring alternative/additional antibiotic therapy was considered a failure. Failed subjects must have had 3 full days of therapy administered. | During treatment at day 5 +/- 1 day | 
| Number of Subjects Achieving Bacteriological Success During Treatment in the Per Protocol Population With Causative Organism(s) | Bacteriological success = response classified as 'eradication' or 'presumed eradication' without occurrence of a superinfection. Bacteriological failure = response classified as 'persistence', 'presumed persistence', or 'superinfection'. | During treatment at day 5 +/- 1 day | 
| Number of Subjects Achieving Clinical Cure at End of Therapy (EOT) Visit in the Per Protocol Population | Clinical cure = resolution/improvement of clinical signs and symptoms related to the infection without wound infection requiring systemic antibiotic treatment. Clinical failure = Failure to respond/insufficient lessening of signs and symptoms of infection requiring a modification/addition of antibacterial therapy, or a second surgical intervention (unless the original surgery was deemed inadequate). Development of a wound infection requiring alternative/additional antibiotic therapy was considered a failure. Failed subjects must have had 3 full days of therapy administered. | after 5 - 14 days of therapy | 
| Number of Subjects Achieving Bacteriological Success at EOT Visit in the Per Protocol Population With Causative Organism(s) | Bacteriological success = response classified as 'eradication' or 'presumed eradication' without occurrence of a superinfection. Bacteriological failure = response classified as 'persistence', 'presumed persistence', or 'superinfection'. | After 5 - 14 days of therapy | 
| Number of Subjects Achieving Bacteriological Success at TOC Visit in the Per Protocol Population With Causative Organism(s) | Bacteriological success = response classified as 'eradication' or 'presumed eradication' without occurrence of a superinfection. Bacteriological failure = response classified as 'persistence', 'presumed persistence', or 'superinfection' - additionally, any recurrence or reinfection was treated as bacteriological failure at TOC. | 21 - 28 days after end of therapy | 
| Number of Subjects Achieving Clinical Cure at TOC Visit in the Per Protocol Population With Causative Organism(s) | Clinical cure at TOC = resolution or improvement of clinical signs and symptoms related to the infection without the occurrence of a wound infection requiring a systemic antibiotic treatment. Clinical failure at TOC = either failure to respond or insufficient lessening of the signs and symptoms of infection at end of treatment (EOT) or reappearance of the signs and symptoms of the original infection from EOT up to TOC or wound infection requiring additional systemic antimicrobial therapy at any time up to TOC. | 21 - 28 days after end of therapy | 
| Number of Subjects Who Died Due to Intra-abdominal Infections | Number of subjects who had died due to intra abdominal infections by the time of TOC visit. | 21 - 28 days after end of treatment at TOC Visit | 
| Duration of Hospitalization | Duration of hospitalization in the per protocol population. | From the first admission date to the discharge date (from 4 to 71 days after start of study medication) | 
| Duration of Hospitalization Postoperatively | Duration of hospitalization after the first surgery until discharge in the per protocol population. | Duration of hospitalization after the first surgery until discharge date (from 4 to 71 days after start of study medication) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Complicated Intra-Abdominal Infections