Clinical trial NCT00492726: Therapy of Complicated Intra-Abdominal Infections With Moxifloxacin or Ertapenem
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Infection
Keywords: Complicated Intra-Abdominal Infections
Lead sponsor: Bayer
Sponsor class: INDUSTRY
First posted: 2007-06-27
Enrollment: 804
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


Eligibility criteria: 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

Primary outcomes:
measure: Number of Subjects Achieving Clinical Cure at Test of Cure (TOC) Visit in the Per Protocol Population
timeFrame: 21 to 28 days after completion of study drug therapy
Secondary outcomes:
measure: Number of Subjects Achieving Clinical Improvement During Treatment in the Per Protocol Population
timeFrame: During treatment at day 5 +/- 1 day
measure: Number of Subjects Achieving Bacteriological Success During Treatment in the Per Protocol Population With Causative Organism(s)
timeFrame: During treatment at day 5 +/- 1 day
measure: Number of Subjects Achieving Clinical Cure at End of Therapy (EOT) Visit in the Per Protocol Population
timeFrame: after 5 - 14 days of therapy
measure: Number of Subjects Achieving Bacteriological Success at EOT Visit in the Per Protocol Population With Causative Organism(s)
timeFrame: After 5 - 14 days of therapy
measure: Number of Subjects Achieving Bacteriological Success at TOC Visit in the Per Protocol Population With Causative Organism(s)
timeFrame: 21 - 28 days after end of therapy
measure: Number of Subjects Achieving Clinical Cure at TOC Visit in the Per Protocol Population With Causative Organism(s)
timeFrame: 21 - 28 days after end of therapy
measure: Number of Subjects Who Died Due to Intra-abdominal Infections
timeFrame: 21 - 28 days after end of treatment at TOC Visit
measure: Duration of Hospitalization
timeFrame: From the first admission date to the discharge date (from 4 to 71 days after start of study medication)
measure: Duration of Hospitalization Postoperatively
timeFrame: Duration of hospitalization after the first surgery until discharge date (from 4 to 71 days after start of study medication)
Other outcomes:
Locations:
city: Ciudadela
country: Argentina
state: Buenos Aires
city: de Febrero 3
country: Argentina
state: Buenos Aires
city: Florencio Varela
country: Argentina
state: Buenos Aires
city: Merlo
country: Argentina
state: Buenos Aires
city: Buenos Aires
country: Argentina
state: Ciudad Auton. de Buenos Aires
city: Rosario
country: Argentina
state: Santa Fe
city: Capital Federal
country: Argentina
city: Córdoba
country: Argentina
city: Mendoza
country: Argentina
city: Bruxelles - Brussel
country: Belgium
city: Bruxelles - Brussel
country: Belgium
city: Gent
country: Belgium
city: Pleven
country: Bulgaria
city: Rousse
country: Bulgaria
city: Sofia
country: Bulgaria
city: Sofia
country: Bulgaria
city: Kohtla-Jarve
country: Estonia
city: Tallin
country: Estonia
city: Tartu
country: Estonia
city: Amilly Cedex
country: France
city: Besancon
country: France
city: Heidelberg
country: Germany
state: Baden-Württemberg
city: Beeskow
country: Germany
state: Brandenburg
city: Hannover
country: Germany
state: Niedersachsen
city: Paderborn
country: Germany
state: Nordrhein-Westfalen
city: Homburg
country: Germany
state: Saarland
city: Rio Patras
country: Greece
city: Haifa
country: Israel
city: Kfar Saba
country: Israel
city: Daugavpils
country: Latvia
city: Liepaja
country: Latvia
city: Rezekne
country: Latvia
city: Riga
country: Latvia
city: Riga
country: Latvia
city: Valmiera
country: Latvia
city: Kaunas
country: Lithuania
city: Klaipeda
country: Lithuania
city: Vilnius
country: Lithuania
city: Vilnius
country: Lithuania
city: Brasov
country: Romania
city: Bucharest
country: Romania
city: Cluj-Napoca
country: Romania
city: Oradea
country: Romania
city: Timisoara
country: Romania
city: Moscow
country: Russian Federation
city: Moscow
country: Russian Federation
city: Smolensk
country: Russian Federation
city: Cape Town
country: South Africa
state: Cape
city: Pretoria
country: South Africa
state: Gauteng
city: Somerset West
country: South Africa
state: Western Cape
city: L'Hospitalet de Llobregat
country: Spain
state: Barcelona
city: Madrid
country: Spain
Study officials:
affiliation: Bayer
name: Bayer Study Director
role: STUDY_DIRECTOR
References:
citation: De Waele JJ, Tellado JM, Alder J, Reimnitz P, Jensen M, Hampel B, Arvis P. Randomised clinical trial of moxifloxacin versus ertapenem in complicated intra-abdominal infections: results of the PROMISE study. Int J Antimicrob Agents. 2013 Jan;41(1):57-64. doi: 10.1016/j.ijantimicag.2012.08.013. Epub 2012 Nov 13.