Therapy of Complicated Intra-Abdominal Infections With Moxifloxacin or Ertapenem

• Sponsor: Bayer (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00492726
• Collaborator: (none)
• Enrollment: 804
• Locations: 52
• Arms: 2
• Duration (Months): 31.1
• Patients Per Site: 15.5
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Infection	Drug: Moxifloxacin (Avelox, BAY12-8039); Drug: Ertapenem intravenous	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 804 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• 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 Start Date: Jul 1, 2006
• Actual Primary Completion Date: Feb 1, 2009
• Actual Study Completion Date: Feb 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Drug: Moxifloxacin (Avelox, BAY12-8039); Moxifloxacin, 400mg, administered intravenously once daily
Active Comparator: Ertapenem Subject received Ertapenem 1.0 g in 50 mL for intravenous infusion and placebo matching Moxifloxacin (Moxifloxacin dummy) every 24 hours.	Drug: Ertapenem intravenous; Active treatment: Ertapenem 1.0g, administered intravenously once daily

Outcome Measures

Primary Outcome Measures

1. 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

1. 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.

2. 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'.

3. 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.

4. 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'.

5. 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.

6. 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.

7. 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.

8. 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.

9. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Ciudadela	Buenos Aires	Argentina	B1702FWM
2		de Febrero 3	Buenos Aires	Argentina	1657
3		Florencio Varela	Buenos Aires	Argentina	1888
4		Merlo	Buenos Aires	Argentina	B1712FJN
5		Buenos Aires	Ciudad Auton. de Buenos Aires	Argentina	C1180AAX
6		Rosario	Santa Fe	Argentina
7		Capital Federal		Argentina
8		Córdoba		Argentina	5000
9		Mendoza		Argentina
10		Bruxelles - Brussel		Belgium	1070
11		Bruxelles - Brussel		Belgium	1090
12		Gent		Belgium	9000
13		Pleven		Bulgaria	5800
14		Rousse		Bulgaria	7002
15		Sofia		Bulgaria	1431
16		Sofia		Bulgaria	1606
17		Kohtla-Jarve		Estonia	30322
18		Tallin		Estonia	EE-13419
19		Tartu		Estonia	EE-51014
20		Amilly Cedex		France	45207
21		Besancon		France	25000
22		Heidelberg	Baden-Württemberg	Germany	69120
23		Beeskow	Brandenburg	Germany	15848
24		Hannover	Niedersachsen	Germany	30625
25		Paderborn	Nordrhein-Westfalen	Germany	33098
26		Homburg	Saarland	Germany	66424
27		Rio Patras		Greece	265 00
28		Haifa		Israel	31048
29		Kfar Saba		Israel	4428164
30		Daugavpils		Latvia	LV-5417
31		Liepaja		Latvia	3402
32		Rezekne		Latvia
33		Riga		Latvia	1002
34		Riga		Latvia	LV-1038
35		Valmiera		Latvia	LV-4201
36		Kaunas		Lithuania	45130
37		Klaipeda		Lithuania	LT-92231
38		Vilnius		Lithuania	10207
39		Vilnius		Lithuania	LT-04130
40		Brasov		Romania
41		Bucharest		Romania	022328
42		Cluj-Napoca		Romania	400006
43		Oradea		Romania
44		Timisoara		Romania	300748
45		Moscow		Russian Federation	115280
46		Moscow		Russian Federation	119048
47		Smolensk		Russian Federation	214019
48		Cape Town	Cape	South Africa	7500
49		Pretoria	Gauteng	South Africa	0001
50		Somerset West	Western Cape	South Africa	7130
51		L'Hospitalet de Llobregat	Barcelona	Spain	08907
52		Madrid		Spain	28007

Sponsors and Collaborators

• Bayer

Investigators

• Study Director: Bayer Study Director, Bayer

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Click here and search for information of Bayer products for Europe

Publications

None provided.

• Responsible Party: Bayer
• ClinicalTrials.gov Identifier: NCT00492726
• Other Study ID Numbers: 11976; 2006-000874-56
• First Posted: Jun 27, 2007
• Last Update Posted: Nov 7, 2014
• Last Verified: Nov 1, 2014

• Keywords provided by Bayer: Complicated Intra-Abdominal Infections
• Additional relevant MeSH terms: Infections; Communicable Diseases; Intraabdominal Infections; Moxifloxacin; Ertapenem; Norgestimate, ethinyl estradiol drug combination

Study Results

Participant Flow

Recruitment Details	Subjects were enrolled from 02 July 2006 to 31 December 2008 at 52 centers in 14 countries: Argentina (9), Belgium (3), Bulgaria (4), Estonia (3), France (2 ), Germany (5), Greece (1), Israel (2), Latvia (6), Lithuania (4), Romania (5), Russia (3), South Africa (3), and Spain (2).
Pre-assignment Detail	830 subjects screened, 804 randomized. 6 not treated. Safety/Intent to treat population = 798 subjects with at least 1 dose taken and 1 observation after intake (Moxifloxacin 408; Ertapenem 390). Per protocol population = 699 subjects with no major protocol deviations that would have influenced the primary outcome (Moxifloxacin 352; Ertapenem 347).

Arm/Group Title	Moxifloxacin (Avelox, BAY12-8039)	Ertapenem
Arm/Group Description	Subjects received placebo matching the comparator (Ertapenem dummy) and Moxifloxacin 400 mg in 250 mL for intravenous infusion every 24 hours.	Subject received Ertapenem 1.0 g in 50 mL for intravenous infusion and placebo matching Moxifloxacin (Moxifloxacin dummy) every 24 hours.
Period Title: Overall Study
STARTED	410	394
End of Treatment (EOT, Day 5 to 14)	387	377
End of Study	360	358
COMPLETED	360	358
NOT COMPLETED	50	36

Baseline Characteristics

Arm/Group Title	Moxifloxacin (Avelox, BAY12-8039)	Ertapenem	Total
Arm/Group Description	Subjects received placebo matching the comparator (Ertapenem dummy) and Moxifloxacin 400 mg in 250 mL for intravenous infusion every 24 hours.	Subject received Ertapenem 1.0 g in 50 mL for intravenous infusion and placebo matching Moxifloxacin (Moxifloxacin dummy) every 24 hours.	Total of all reporting groups
Overall Participants	410	394	804
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	48.1 (18.3)	47.0 (18.2)	47.4 (18.2)
Sex: Female, Male (Count of Participants)
Female	156 38%	131 33.2%	287 35.7%
Male	254 62%	263 66.8%	517 64.3%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

The per protocol population was the main analysis set for the assessment of clinical response and was defined as those subjects with no major protocol deviations that would have influenced the primary outcome.

Arm/Group Title	Moxifloxacin (Avelox, BAY12-8039)	Ertapenem
Arm/Group Description	Subjects received placebo matching the comparator (Ertapenem dummy) and Moxifloxacin 400 mg in 250 mL for intravenous infusion every 24 hours.	Subject received Ertapenem 1.0 g in 50 mL for intravenous infusion and placebo matching Moxifloxacin (Moxifloxacin dummy) every 24 hours.
Measure Participants	352	347
Clinical Cure	315 76.8%	324 82.2%
Clinical Failure	37 9%	23 5.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Moxifloxacin (Avelox, BAY12-8039), Ertapenem
	Comments	Calculated were 95% confidence intervals for the difference in success rates between treatment groups (moxifloxacin minus comparator).
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	The non-inferiority margin was set to 10% in the protocol, in agreement with FDA recommendations. Sample size was estimated using the method as described in Farrington-Manning. Estimation was performed to achieve 85% power, based on the equivalence delta of 10%, and a clinical success rate of 80% in the per protocol population.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference of cure rates (in percent)
	Estimated Value	-3.8
	Confidence Interval	() 95%; -7.9 to 0.4
	Parameter Dispersion	Type: Value:
	Estimation Comments	A positive value indicates an advantage for the treatment group of moxifloxacin, a negative value an advantage for the comparator group.

2. Secondary Outcome

Title	Number of Subjects Achieving Clinical Improvement During Treatment in the Per Protocol Population
Description	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.
Time Frame	During treatment at day 5 +/- 1 day

Outcome Measure Data

Analysis Population Description

Per protocol population comprising subjects with no major protocol deviations that would have influenced the primary outcome.

Arm/Group Title	Moxifloxacin (Avelox, BAY12-8039)	Ertapenem
Arm/Group Description	Subjects received placebo matching the comparator (Ertapenem dummy) and Moxifloxacin 400 mg in 250 mL for intravenous infusion every 24 hours.	Subject received Ertapenem 1.0 g in 50 mL for intravenous infusion and placebo matching Moxifloxacin (Moxifloxacin dummy) every 24 hours.
Measure Participants	352	347
Clinical Improvement	210 51.2%	194 49.2%
Clinical Failure	0 0%	2 0.5%
Missing	142 34.6%	151 38.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Moxifloxacin (Avelox, BAY12-8039), Ertapenem
	Comments	Calculated were 95% confidence intervals for the difference in success rates between treatment groups (moxifloxacin minus comparator).
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Sample size estimation was based on the primary efficacy variable.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in improvement rates (in %)
	Estimated Value	1.1
	Confidence Interval	() 95%; -0.4 to 2.7
	Parameter Dispersion	Type: Value:
	Estimation Comments	A positive value indicates an advantage for the treatment group of moxifloxacin, a negative value an advantage for the comparator group.

3. Secondary Outcome

Title	Number of Subjects Achieving Bacteriological Success During Treatment in the Per Protocol Population With Causative Organism(s)
Description	Bacteriological success = response classified as 'eradication' or 'presumed eradication' without occurrence of a superinfection. Bacteriological failure = response classified as 'persistence', 'presumed persistence', or 'superinfection'.
Time Frame	During treatment at day 5 +/- 1 day

Outcome Measure Data

Analysis Population Description

Per protocol population (subjects with no major protocol deviations that would have influenced the primary outcome) with causative organism(s).

Arm/Group Title	Moxifloxacin (Avelox, BAY12-8039)	Ertapenem
Arm/Group Description	Subjects received placebo matching the comparator (Ertapenem dummy) and Moxifloxacin 400 mg in 250 mL for intravenous infusion every 24 hours.	Subject received Ertapenem 1.0 g in 50 mL for intravenous infusion and placebo matching Moxifloxacin (Moxifloxacin dummy) every 24 hours.
Measure Participants	297	276
Eradication	5 1.2%	5 1.3%
Presumed Eradication	170 41.5%	149 37.8%
Persistence	16 3.9%	7 1.8%
Presumed Persistence	0 0%	2 0.5%
Superinfections	0 0%	1 0.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Moxifloxacin (Avelox, BAY12-8039), Ertapenem
	Comments	Calculated were 95% confidence intervals for the difference in success rates between treatment groups (moxifloxacin minus comparator).
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Sample size estimation was based on the primary efficacy variable.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in bact. success rates (in %)
	Estimated Value	-3.9
	Confidence Interval	() 95%; -8.8 to 1.0
	Parameter Dispersion	Type: Value:
	Estimation Comments	A positive value indicates an advantage for the treatment group of moxifloxacin, a negative value an advantage for the comparator group. Presumed eradications and eradications without superinfection were considered bacteriological successes.

4. Secondary Outcome

Title	Number of Subjects Achieving Clinical Cure at End of Therapy (EOT) Visit in the Per Protocol Population
Description	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.
Time Frame	after 5 - 14 days of therapy

Outcome Measure Data

Analysis Population Description

Per protocol population comprising subjects with no major protocol deviations that would have influenced the primary outcome.

Arm/Group Title	Moxifloxacin (Avelox, BAY12-8039)	Ertapenem
Arm/Group Description	Subjects received placebo matching the comparator (Ertapenem dummy) and Moxifloxacin 400 mg in 250 mL for intravenous infusion every 24 hours.	Subject received Ertapenem 1.0 g in 50 mL for intravenous infusion and placebo matching Moxifloxacin (Moxifloxacin dummy) every 24 hours.
Measure Participants	352	347
Clinical Cure	328 80%	330 83.8%
Clinical Failure	23 5.6%	17 4.3%
Missing	1 0.2%	0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Moxifloxacin (Avelox, BAY12-8039), Ertapenem
	Comments	Calculated were 95% confidence intervals for the difference in success rates between treatment groups (moxifloxacin minus comparator).
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Sample size estimation was based on the primary efficacy variable.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference of cure rates (in percent)
	Estimated Value	-1.5
	Confidence Interval	() 95%; -5.0 to 1.9
	Parameter Dispersion	Type: Value:
	Estimation Comments	A positive value indicates an advantage for the treatment group of moxifloxacin, a negative value an advantage for the comparator group.

5. Secondary Outcome

Title	Number of Subjects Achieving Bacteriological Success at EOT Visit in the Per Protocol Population With Causative Organism(s)
Description	Bacteriological success = response classified as 'eradication' or 'presumed eradication' without occurrence of a superinfection. Bacteriological failure = response classified as 'persistence', 'presumed persistence', or 'superinfection'.
Time Frame	After 5 - 14 days of therapy

Outcome Measure Data

Analysis Population Description

Per protocol population (subjects with no major protocol deviations that would have influenced the primary outcome) with causative organism(s). For one patient in the Moxifloxacin group, the data is missing due to missing EOT visit (not displayed in the table below).

Arm/Group Title	Moxifloxacin (Avelox, BAY12-8039)	Ertapenem
Arm/Group Description	Subjects received placebo matching the comparator (Ertapenem dummy) and Moxifloxacin 400 mg in 250 mL for intravenous infusion every 24 hours.	Subject received Ertapenem 1.0 g in 50 mL for intravenous infusion and placebo matching Moxifloxacin (Moxifloxacin dummy) every 24 hours.
Measure Participants	297	276
Eradication	5 1.2%	7 1.8%
Presumed Eradication	257 62.7%	247 62.7%
Persistence	20 4.9%	9 2.3%
Presumed Persistence	13 3.2%	11 2.8%
Superinfections	1 0.2%	2 0.5%
Indeterminate/missing	1 0.2%	0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Moxifloxacin (Avelox, BAY12-8039), Ertapenem
	Comments	Calculated were 95% confidence intervals for the difference in success rates between treatment groups (moxifloxacin minus comparator).
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Sample size estimation was based on the primary efficacy variable.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in bact. success rates (in %)
	Estimated Value	-3.9
	Confidence Interval	() 95%; -8.8 to 1.0
	Parameter Dispersion	Type: Value:
	Estimation Comments	A positive value indicates an advantage for the treatment group of moxifloxacin, a negative value an advantage for the comparator group. Presumed eradications and eradications without superinfection were considered bacteriological successes.

6. Secondary Outcome

Title	Number of Subjects Achieving Bacteriological Success at TOC Visit in the Per Protocol Population With Causative Organism(s)
Description	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.
Time Frame	21 - 28 days after end of therapy

Outcome Measure Data

Analysis Population Description

Per protocol population (subjects with no major protocol deviations that would have influenced the primary outcome) with causative organism(s).

Arm/Group Title	Moxifloxacin (Avelox, BAY12-8039)	Ertapenem
Arm/Group Description	Subjects received placebo matching the comparator (Ertapenem dummy) and Moxifloxacin 400 mg in 250 mL for intravenous infusion every 24 hours.	Subject received Ertapenem 1.0 g in 50 mL for intravenous infusion and placebo matching Moxifloxacin (Moxifloxacin dummy) every 24 hours.
Measure Participants	297	276
Eradication	0 0%	0 0%
Presumed Eradication	257 62.7%	249 63.2%
Persistence	20 4.9%	9 2.3%
Presumed Persistence	20 4.9%	18 4.6%
Superinfections	0 0%	0 0%
Reinfections	0 0%	0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Moxifloxacin (Avelox, BAY12-8039), Ertapenem
	Comments	Calculated were 95% confidence intervals for the difference in success rates between treatment groups (moxifloxacin minus comparator).
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Sample size estimation was based on the primary efficacy variable.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in bact. success rates (in %)
	Estimated Value	-3.8
	Confidence Interval	() 95%; -9.0 to 1.5
	Parameter Dispersion	Type: Value:
	Estimation Comments	A positive value indicates an advantage for the treatment group of moxifloxacin, a negative value an advantage for the comparator group. Presumed eradications and eradications without super- or reinfection were considered bacteriological successes.

7. Secondary Outcome

Title	Number of Subjects Achieving Clinical Cure at TOC Visit in the Per Protocol Population With Causative Organism(s)
Description	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.
Time Frame	21 - 28 days after end of therapy

Outcome Measure Data

Analysis Population Description

Per protocol population (subjects with no major protocol deviations that would have influenced the primary outcome) with causative organism(s).

Arm/Group Title	Moxifloxacin (Avelox, BAY12-8039)	Ertapenem
Arm/Group Description	Subjects received placebo matching the comparator (Ertapenem dummy) and Moxifloxacin 400 mg in 250 mL for intravenous infusion every 24 hours.	Subject received Ertapenem 1.0 g in 50 mL for intravenous infusion and placebo matching Moxifloxacin (Moxifloxacin dummy) every 24 hours.
Measure Participants	297	276
Clinical Cure	265 64.6%	254 64.5%
Clinical Failure	32 7.8%	22 5.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Moxifloxacin (Avelox, BAY12-8039), Ertapenem
	Comments	Calculated were 95% confidence intervals for the difference in success rates between treatment groups (moxifloxacin minus comparator).
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Sample size estimation was based on the primary efficacy variable.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference of cure rates (in percent)
	Estimated Value	-2.9
	Confidence Interval	() 95%; -7.6 to 1.9
	Parameter Dispersion	Type: Value:
	Estimation Comments	A positive value indicates an advantage for the treatment group of moxifloxacin, a negative value an advantage for the comparator group.

8. Secondary Outcome

Title	Number of Subjects Who Died Due to Intra-abdominal Infections
Description	Number of subjects who had died due to intra abdominal infections by the time of TOC visit.
Time Frame	21 - 28 days after end of treatment at TOC Visit

Outcome Measure Data

Analysis Population Description

Per protocol population comprising subjects with no major protocol deviations that would have influenced the primary outcome.

Arm/Group Title	Moxifloxacin (Avelox, BAY12-8039)	Ertapenem
Arm/Group Description	Subjects received placebo matching the comparator (Ertapenem dummy) and Moxifloxacin 400 mg in 250 mL for intravenous infusion every 24 hours.	Subject received Ertapenem 1.0 g in 50 mL for intravenous infusion and placebo matching Moxifloxacin (Moxifloxacin dummy) every 24 hours.
Measure Participants	352	347
Yes	3 0.7%	1 0.3%
No	349 85.1%	346 87.8%

9. Secondary Outcome

Title	Duration of Hospitalization
Description	Duration of hospitalization in the per protocol population.
Time Frame	From the first admission date to the discharge date (from 4 to 71 days after start of study medication)

Outcome Measure Data

Analysis Population Description

Numbers refer to patients in the per protocol population with known end of hospitalization date.

Arm/Group Title	Moxifloxacin (Avelox, BAY12-8039)	Ertapenem
Arm/Group Description	Subjects received placebo matching the comparator (Ertapenem dummy) and Moxifloxacin 400 mg in 250 mL for intravenous infusion every 24 hours.	Subject received Ertapenem 1.0 g in 50 mL for intravenous infusion and placebo matching Moxifloxacin (Moxifloxacin dummy) every 24 hours.
Measure Participants	346	343
Mean (Standard Deviation) [days]	11.7 (7.3)	11.2 (7.8)

10. Secondary Outcome

Title	Duration of Hospitalization Postoperatively
Description	Duration of hospitalization after the first surgery until discharge in the per protocol population.
Time Frame	Duration of hospitalization after the first surgery until discharge date (from 4 to 71 days after start of study medication)

Outcome Measure Data

Analysis Population Description

Numbers refer to patients in the per protocol population with known end of hospitalization date.

Arm/Group Title	Moxifloxacin (Avelox, BAY12-8039)	Ertapenem
Arm/Group Description	Subjects received placebo matching the comparator (Ertapenem dummy) and Moxifloxacin 400 mg in 250 mL for intravenous infusion every 24 hours.	Subject received Ertapenem 1.0 g in 50 mL for intravenous infusion and placebo matching Moxifloxacin (Moxifloxacin dummy) every 24 hours.
Measure Participants	346	343
Mean (Standard Deviation) [days]	11.1 (7.1)	10.7 (7.2)

Adverse Events

Arm/Group Title	Moxifloxacin (Avelox, BAY12-8039)		Ertapenem
Arm/Group Description	Subjects received placebo matching the comparator (Ertapenem dummy) and Moxifloxacin 400 mg in 250 mL for intravenous infusion every 24 hours.		Subject received Ertapenem 1.0 g in 50 mL for intravenous infusion and placebo matching Moxifloxacin (Moxifloxacin dummy) every 24 hours.
All Cause Mortality
	Moxifloxacin (Avelox, BAY12-8039)		Ertapenem
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Moxifloxacin (Avelox, BAY12-8039)		Ertapenem
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	60/408 (14.7%)		48/390 (12.3%)
Cardiac disorders
Acute mycardial infarction	2/408 (0.5%)	2	0/390 (0%)	0
Atrial fibrillation	0/408 (0%)	0	2/390 (0.5%)	2
Atrial flutter	1/408 (0.2%)	1	0/390 (0%)	0
Cardiac arrest	7/408 (1.7%)	7	2/390 (0.5%)	3
Cardiac failure acute	1/408 (0.2%)	1	1/390 (0.3%)	1
Cardio-respiratory arrest	2/408 (0.5%)	2	0/390 (0%)	0
Cardiogenic shock	0/408 (0%)	0	1/390 (0.3%)	1
Ventricular tachycardia	1/408 (0.2%)	1	0/390 (0%)	0
Tachyarrhythmia	0/408 (0%)	0	1/390 (0.3%)	1
Cardiopulmonary failure	1/408 (0.2%)	1	0/390 (0%)	0
Gastrointestinal disorders
Colonic fistula	1/408 (0.2%)	1	0/390 (0%)	0
Duodenal ulcer perforation	1/408 (0.2%)	1	0/390 (0%)	0
Duodenitis	0/408 (0%)	0	1/390 (0.3%)	1
Gastric haemorrhage	0/408 (0%)	0	1/390 (0.3%)	1
Gastrointestinal fistula	1/408 (0.2%)	1	0/390 (0%)	0
Gastrointestinal haemorrhage	1/408 (0.2%)	1	0/390 (0%)	0
Ileus	0/408 (0%)	0	1/390 (0.3%)	1
Inguinal hernia	0/408 (0%)	0	1/390 (0.3%)	1
Intestinal fistula	1/408 (0.2%)	1	3/390 (0.8%)	4
Intestinal obstruction	2/408 (0.5%)	2	0/390 (0%)	0
Large intestine perforation	1/408 (0.2%)	1	0/390 (0%)	0
Nausea	1/408 (0.2%)	1	0/390 (0%)	0
Peritonitis	3/408 (0.7%)	3	2/390 (0.5%)	2
Small intestinal obstruction	0/408 (0%)	0	1/390 (0.3%)	1
Upper gastrointestinal haemorrhage	0/408 (0%)	0	1/390 (0.3%)	1
Vomiting	1/408 (0.2%)	1	0/390 (0%)	0
Mechanical ileus	1/408 (0.2%)	1	0/390 (0%)	0
Jejunal fistula	1/408 (0.2%)	1	0/390 (0%)	0
General disorders
Impaired healing	1/408 (0.2%)	1	0/390 (0%)	0
Multi-organ failure	4/408 (1%)	4	2/390 (0.5%)	2
Unevaluable event	4/408 (1%)	4	2/390 (0.5%)	2
Hepatobiliary disorders
Acute hepatic failure	1/408 (0.2%)	1	0/390 (0%)	0
Portal vein thrombosis	1/408 (0.2%)	1	0/390 (0%)	0
Infections and infestations
Abdominal wall abscess	2/408 (0.5%)	2	0/390 (0%)	0
Abscess intestinal	0/408 (0%)	0	1/390 (0.3%)	1
Bronchopneumonia	0/408 (0%)	0	1/390 (0.3%)	1
Clostridium difficile colitis	1/408 (0.2%)	1	1/390 (0.3%)	1
Disseminated tuberculosis	1/408 (0.2%)	1	0/390 (0%)	0
Empyema	1/408 (0.2%)	1	0/390 (0%)	0
Gastroenteritis	1/408 (0.2%)	1	0/390 (0%)	0
Peritoneal abscess	1/408 (0.2%)	1	0/390 (0%)	0
Pneumonia	1/408 (0.2%)	1	4/390 (1%)	4
Postoperative wound infection	2/408 (0.5%)	2	2/390 (0.5%)	2
Retroperitoneal abscess	1/408 (0.2%)	1	0/390 (0%)	0
Sepsis	3/408 (0.7%)	3	1/390 (0.3%)	1
Septic shock	3/408 (0.7%)	3	0/390 (0%)	0
Wound infection	10/408 (2.5%)	10	1/390 (0.3%)	1
Rectal abscess	0/408 (0%)	0	1/390 (0.3%)	1
Appendiceal abscess	0/408 (0%)	0	2/390 (0.5%)	2
Haematoma infection	1/408 (0.2%)	1	1/390 (0.3%)	1
Subdiaphragmatic abscess	0/408 (0%)	0	1/390 (0.3%)	1
Abdominal infection	1/408 (0.2%)	1	1/390 (0.3%)	1
Wound sepsis	0/408 (0%)	0	1/390 (0.3%)	1
Wound abscess	0/408 (0%)	0	1/390 (0.3%)	1
Abdominal abscess	2/408 (0.5%)	2	1/390 (0.3%)	1
Soft tissue infection	0/408 (0%)	0	1/390 (0.3%)	1
Post procedural sepsis	1/408 (0.2%)	1	0/390 (0%)	0
Injury, poisoning and procedural complications
Failure to anastomose	0/408 (0%)	0	1/390 (0.3%)	1
Hand fracture	0/408 (0%)	0	1/390 (0.3%)	1
Wound dehiscence	2/408 (0.5%)	2	1/390 (0.3%)	1
Postoperative ileus	0/408 (0%)	0	1/390 (0.3%)	1
Wound evisceration	2/408 (0.5%)	2	0/390 (0%)	0
Postoperative respiratory distress	0/408 (0%)	0	1/390 (0.3%)	1
Post procedural bile leak	0/408 (0%)	0	1/390 (0.3%)	1
Procedural complication	0/408 (0%)	0	1/390 (0.3%)	1
Anastomotic complication	0/408 (0%)	0	1/390 (0.3%)	1
Gastrointestinal disorder postoperative	0/408 (0%)	0	1/390 (0.3%)	1
Intestinal anastomosis complication	1/408 (0.2%)	1	0/390 (0%)	0
Investigations
Chest X-ray abnormal	0/408 (0%)	0	1/390 (0.3%)	1
Hepatic enzyme increased	2/408 (0.5%)	2	0/390 (0%)	0
Metabolism and nutrition disorders
Dehydration	0/408 (0%)	0	1/390 (0.3%)	1
Hypoglycaemia	1/408 (0.2%)	1	0/390 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
B-cell lymphoma	0/408 (0%)	0	1/390 (0.3%)	1
Colon cancer	1/408 (0.2%)	1	0/390 (0%)	0
Hairy cell leukaemia	1/408 (0.2%)	1	0/390 (0%)	0
Nervous system disorders
Cerebrovascular accident	1/408 (0.2%)	1	0/390 (0%)	0
Coma	1/408 (0.2%)	1	0/390 (0%)	0
Convulsion	0/408 (0%)	0	1/390 (0.3%)	1
Hemiplegia	1/408 (0.2%)	1	0/390 (0%)	0
Subarachnoid haemorrhage	1/408 (0.2%)	1	0/390 (0%)	0
Ischaemic stroke	1/408 (0.2%)	1	0/390 (0%)	0
Psychiatric disorders
Agitation	1/408 (0.2%)	1	0/390 (0%)	0
Renal and urinary disorders
Renal failure	0/408 (0%)	0	1/390 (0.3%)	1
Renal failure acute	4/408 (1%)	4	1/390 (0.3%)	1
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome	3/408 (0.7%)	3	1/390 (0.3%)	1
Acute respiratory failure	2/408 (0.5%)	2	1/390 (0.3%)	1
Apnoea	1/408 (0.2%)	1	0/390 (0%)	0
Aspiration	0/408 (0%)	0	1/390 (0.3%)	1
Pleural effusion	3/408 (0.7%)	3	0/390 (0%)	0
Pleurisy	0/408 (0%)	0	1/390 (0.3%)	1
Pulmonary embolism	2/408 (0.5%)	2	2/390 (0.5%)	2
Respiratory arrest	0/408 (0%)	0	1/390 (0.3%)	1
Respiratory distress	1/408 (0.2%)	1	0/390 (0%)	0
Respiratory failure	3/408 (0.7%)	3	1/390 (0.3%)	1
Hydropneumothorax	0/408 (0%)	0	1/390 (0.3%)	1
Vascular disorders
Hypotension	0/408 (0%)	0	1/390 (0.3%)	1
Shock	0/408 (0%)	0	1/390 (0.3%)	1
Deep vein thrombosis	1/408 (0.2%)	1	0/390 (0%)	0
Cardiovascular insufficiency	0/408 (0%)	0	1/390 (0.3%)	1
Other (Not Including Serious) Adverse Events
	Moxifloxacin (Avelox, BAY12-8039)		Ertapenem
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	115/408 (28.2%)		87/390 (22.3%)
Gastrointestinal disorders
Diarrhoea	23/408 (5.6%)	23	18/390 (4.6%)	18
Nausea	30/408 (7.4%)	33	17/390 (4.4%)	18
Infections and infestations
Wound infection	37/408 (9.1%)	37	28/390 (7.2%)	28
Investigations
Lipase increased	25/408 (6.1%)	25	24/390 (6.2%)	24

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The agreed point of publication is 12/18 months after database lock at the earliest. Bayer will have up to 30/45 days to review publications and may request an additional publication delay of up to 60 days to allow for filing a patent application (if applicable). No publication of single center data should be done prior of publication if multi-center data.