E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Complicated intra-abdominal Infections |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 8.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10056570 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Primary objective is to compare the safety and efficacy of intravenous moxifloxacin 400 mg administered once daily with those of intravenous ertapenem 1 g once a day in adult subjects with cIAI that require surgery and parenteral antibiotic therapy
The primary efficacy variable for this trial is the clinical response 21 to 28 days after the completion of study drug therapy (Test of Cure visit). |
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E.2.2 | Secondary objectives of the trial |
Secondary efficacy parameters are: • Clinical and bacteriological response on treatment Day 5 +/- 1. • Clinical and bacteriological response at the End-of-Therapy (EOT). • Bacteriological response at the TOC visit (21 28 days after EOT). • Clinical response at the TOC visit in subjects with a bacteriologically documented intra abdominal infection. • Mortality attributable to intra abdominal infections at the time of the TOC visit (21 to 28 days after EOT). • Duration of hospitalization (total days). • Duration of hospitalization postoperatively (days).
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Subjects must meet all the following inclusion criteria: 1. Hospitalized men or women >/= 18 years of age. 2. Expected duration of treatment with intravenous antibiotics anticipated to be >/= 5 full days but not exceeding 14 days. 3. Documented and signed written informed consent. Consent may also be provided by a subject’s legally acceptable representative/guardian/parent (in accordance with local law). 4. 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 (ie, 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: 1. Radiological evidence [abdominal plain films, computed tomography (CT), magnetic resonance imaging (MRI) or ultrasound] of gastrointestinal perforation or intra-abdominal abscess and 2. The following signs and symptoms: • At least one symptom referable to the abdominal cavity (eg, nausea, vomiting, distension or pain), lasting for at least 24 hours. • At least one of the following signs: tenderness (with or without rebound), absent or diminished bowel sounds, abdominal wall rigidity • At least two of the following SIRS criteria (23): .Temperature > 38.3°C rectal or tympanic membrane, or temperature > 37.8°C oral or >37.3 for axillary. . Heart rate > 90/min. . Respiratory rate > 20/min. . WBC >12,000 cells/mm3 or < 4,000 cells/ mm3. and 3. The subject must be scheduled for a surgical procedure (laparotomy or laparoscopy) within 24 hours of enrollment in the study.
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E.4 | Principal exclusion criteria |
1) Known hypersensitivity to quinolones, and/or to carbapenems and/or to any other type of beta lactam antibiotic drugs (eg, penicillins or cephalosporins), or any of the excipients. 2) Women who are pregnant or lactating or in whom pregnancy cannot be excluded (Note: a urine pregnancy test has to be performed for all women of childbearing potential before inclusion into the study). 3) History of tendon disease/disorder related to quinolone treatment. 4) 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. 5) Concomitant use of any of the following drugs, reported to increase the QT interval: antiarrhythmics class IA (eg, quinidine, hydroquinidine, disopyramide) or antiarrhythmics class III (eg, amiodarone, sotalol, dofetilide, ibutilide), neuroleptics (eg, 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). 6) Known severe hepatic insufficiency (Child Pugh C, see Appendix 10.2) or transaminase increase > 5 fold upper limit of normal (ULN). 7)Creatinine clearance </= 30 mL/min/1.73 m2 (the Cockroft-Gault formula for calculating creatinine clearance is given in Appendix 10.5). 8) Systemic antibacterial therapy administered for more than 24 hours within 7 days prior to treatment with study medication. 9)Need for systemic antibacterial therapy with agents other than those described in the study protocol (Note: prophylactic anti-fungal therapy is accepted). 10) Indwelling peritoneal catheter or vascular shunt 11)Pre existing ascites and presumed spontaneous bacterial peritonitis. 12) Perforation of the stomach or duodenum, if the duration of perforation (based on first symptoms as reported by the subject) is less than 24 hours or if operated on within 24 hours of perforation. 13) Perforation of the small bowel (excluding the duodenum) or large bowel, if the duration of perforation (based on first symptoms as reported by the subject) is less than 12 hours. 14) All pancreatic processes including pancreatic sepsis, peri-pancreatic sepsis, or an intra abdominal infection secondary to pancreatitis. 15) Liver and splenic abscess. 16) Transmural bowel ischemia or necrosis without perforation or established peritonitis or abscess. 17) Acute and gangrenous cholecystitis without perforation. 18) Acute cholangitis. 19) Early acute, suppurative, or gangrenous non-perforated appendicitis. 20) Subjects requiring antibiotic irrigations (including prophylactic antibiotic irrigations) of the abdominal cavity or surgical wound 21) Treatment with "open abdomen" or marsupialization, or multiple planned re laparotomies. 22) Infections originating from the female genital tract. 23) Peri-nephric infections. 24) Evidence of sepsis with shock requiring the administration of moderately high or high doses of vasopressors for more than 12 consecutive hours. Low doses of vasopressors (e.g.m <5 µg/kg/min for dopamine or <0.2 µg/kg/min noradrenaline) are accepted for any period of time as well as moderately high or high doses of vasopressors for less than 12 consecutive hours, provided that the patients in hemodynamically stable. 25) Known rapidly fatal underlying disease (death expected within 6 months). 26) Neutropenia (neutrophil count < 1,000/µL) caused by immunosuppressive therapy or malignancy. 27) Receiving chronic treatment with known immunosuppressant therapy (including chronic treatment with > 15 mg/day of systemic prednisone or equivalent). 28) Subjects known to have AIDS (CD4 count < 200/µL) or HIV seropositives who are receiving HAART (Note: HIV positive subjects may be included. HIV testing is not required for this study protocol). 29) 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). 30) Subjects with a Body Mass Index >/= 45 kg/m2 [BMI = weight (in kg)/height (in m)2] 31) Previous enrollment in this study. 32) Participation in any clinical investigational drug study within the previous 4 weeks.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy variable for this trial is the clinical response 21 to 28 days after the completion of study drug therapy (Test of Cure visit). |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 35 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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End of Trial is defined as Clean Database |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |