Therapy of Complicated Intra-Abdominal Infections With Moxifloxacin or Ertapenem

Phase 3

Completed

Conditions: Infection

Interventions: Drug: Ertapenem intravenous
Drug: Moxifloxacin (Avelox, BAY12-8039)

Registration Number: NCT00492726

Lead Sponsor: Bayer

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

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 804

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Ertapenem	Ertapenem intravenous	Subject received Ertapenem 1.0 g in 50 mL for intravenous infusion and placebo matching Moxifloxacin (Moxifloxacin dummy) every 24 hours.
Moxifloxacin (Avelox, BAY12-8039)	Moxifloxacin (Avelox, BAY12-8039)	Subjects received placebo matching the comparator (Ertapenem dummy) and Moxifloxacin 400 mg in 250 mL for intravenous infusion every 24 hours.

Primary Outcome Measures

Name	Time	Method
Number of Subjects Achieving Clinical Cure at Test of Cure (TOC) Visit in the Per Protocol Population	21 to 28 days after completion of study drug therapy	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.

Secondary Outcome Measures

Name	Time	Method
Number of Subjects Achieving Clinical Improvement During Treatment in the Per Protocol Population	During treatment at day 5 +/- 1 day	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.
Number of Subjects Achieving Bacteriological Success During Treatment in the Per Protocol Population With Causative Organism(s)	During treatment at day 5 +/- 1 day	Bacteriological success = response classified as 'eradication' or 'presumed eradication' without occurrence of a superinfection. Bacteriological failure = response classified as 'persistence', 'presumed persistence', or 'superinfection'.
Number of Subjects Achieving Clinical Cure at End of Therapy (EOT) Visit in the Per Protocol Population	after 5 - 14 days of therapy	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.
Number of Subjects Achieving Clinical Cure at TOC Visit in the Per Protocol Population With Causative Organism(s)	21 - 28 days after end of therapy	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.
Number of Subjects Achieving Bacteriological Success at EOT Visit in the Per Protocol Population With Causative Organism(s)	After 5 - 14 days of therapy	Bacteriological success = response classified as 'eradication' or 'presumed eradication' without occurrence of a superinfection. Bacteriological failure = response classified as 'persistence', 'presumed persistence', or 'superinfection'.
Number of Subjects Achieving Bacteriological Success at TOC Visit in the Per Protocol Population With Causative Organism(s)	21 - 28 days after end of therapy	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.
Number of Subjects Who Died Due to Intra-abdominal Infections	21 - 28 days after end of treatment at TOC Visit	Number of subjects who had died due to intra abdominal infections by the time of TOC visit.
Duration of Hospitalization	From the first admission date to the discharge date (from 4 to 71 days after start of study medication)	Duration of hospitalization in the per protocol population.
Duration of Hospitalization Postoperatively	Duration of hospitalization after the first surgery until discharge date (from 4 to 71 days after start of study medication)	Duration of hospitalization after the first surgery until discharge in the per protocol population.