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Compare Ceftazidime-Avibactam + Metronidazole Versus Meropenem for Hospitalized Adults With Complicated Intra-Abdominal Infections

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01499290
Recruitment Status : Completed
First Posted : December 26, 2011
Results First Posted : March 1, 2016
Last Update Posted : September 6, 2017
Sponsor:
Collaborator:
Forest Laboratories
Information provided by (Responsible Party):
Pfizer

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Complicated Intra-Abdominal Infection
Interventions Drug: CAZ-AVI
Drug: Metronidazole
Drug: Meropenem
Enrollment 493
Recruitment Details Results from two identical protocols D4280C00001 and D4280C00005 combined into a single database with agreement from FDA and EMA. First patient enrolled 22 March 2012 and last patient's last visit was 07 April 2014. Patients were adults hospitalised with complicated intra-abdominal infection (cIAI) that required surgery and IV antibiotics.
Pre-assignment Details After obtaining written informed consent patients underwent a preliminary evaluation for eligibility within the 24-hour period prior to initiation of IV study therapy. eligible patients were randomized to 1 of 2 treatment groups in a 1:1 ratio according to the central randomization schedule.
Arm/Group Title CAZ-AVI + Metronidazole Meropenem
Hide Arm/Group Description CAZ (2000mg)/AVI (500mg): IV treatment 1000 mg: IV treatment
Period Title: Overall Study
Started 529 [1] 529 [1]
Completed 474 [2] 494 [2]
Not Completed 55 35
Reason Not Completed
Withdrawal by Subject             22             15
Not specified in study report             11             5
Condition improved/subject recovered             1             0
Lack of Efficacy             7             8
Adverse Event             14             7
[1]
Patients dosed in pooled protocols D4280C00001/D4280C00005 (NCT01499290/NCT01500239) agreed with FDA
[2]
(Numbers indicate patients who completed treatment)
Arm/Group Title CAZ-AVI + Metronidazole Meropenem Total
Hide Arm/Group Description CAZ (2000mg)/AVI (500mg): IV treatment 1000 mg: IV treatment Total of all reporting groups
Overall Number of Baseline Participants 520 523 1043
Hide Baseline Analysis Population Description
The MITT analysis set includes all patients who met the disease definition for cIAI and received at least 1 dose of study drug. 15 patients excluded received at least one dose of study drug but failed the minimum disease criteria.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 520 participants 523 participants 1043 participants
49.8  (17.48) 50.3  (18.29) 50.0  (17.88)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 520 participants 523 participants 1043 participants
Female
194
  37.3%
191
  36.5%
385
  36.9%
Male
326
  62.7%
332
  63.5%
658
  63.1%
1.Primary Outcome
Title Clinical Response at the Test of Cure (TOC) Visit in the Microbiologically Modified Intent-To-Treat (mMITT) Analysis Set (Primary Outcome for FDA).
Hide Description The number of patients meeting the cure criteria: complete resolution or significant improvement of signs and symptoms of the index infection such that no further antibacterial therapy, drainage, or surgical intervention is necessary. Indeterminate response are where study data were not available for evaluation of efficacy for any reason, including patient lost to follow-up or assessment not undertaken such that a determination of clinical response could not be made, death where cIAI was clearly noncontributory or circumstances that precluded classification as a cure or failure. Results from two identical protocols D4280C00001 and D4280C00005 combined into a single database with agreement from FDA and EMA.
Time Frame TOC: 28 to 35 days after start of study drug
Hide Outcome Measure Data
Hide Analysis Population Description
The mMITT analysis set included all randomized patients who met the disease definition of cIAI and had at least 1 etiologic pathogen identified at study entry (regardless of isolate susceptibilities). Patients with a bacterial species typically not expected to respond to both study drugs were excluded.
Arm/Group Title CAZ-AVI + Metronidazole Meropenem
Hide Arm/Group Description:
CAZ (2000mg)/AVI (500mg): IV treatment
1000 mg: IV treatment
Overall Number of Participants Analyzed 413 410
Measure Type: Number
Unit of Measure: Participants
Clinical cure 337 349
Clinical failure 37 30
Indeterminate 39 31
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection CAZ-AVI + Metronidazole, Meropenem
Comments The primary objective of this study (FDA agreed) was to determine the noninferiority in the clinical cure rate for CAZ-AVI compared to that for Meropenem at TOC in the mMITT in adult subjects with cIAI.
Type of Statistical Test Non-Inferiority or Equivalence
Comments Non-inferiority was determined by comparing the lower limit of the 95% confidence interval for risk difference (corresponding to a 97.5% 1-sided lower bound) to the non-inferiority marging of -12.5%
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value -3.5
Confidence Interval (2-Sided) 95%
-8.64 to 1.58
Estimation Comments [Not Specified]
2.Primary Outcome
Title Clinical Response at the TOC Visit in the Modified Intent-To-Treat Analysis Set (Co-primary Outcome for Rest of World [ROW]).
Hide Description The number of patients meeting the cure criteria: complete resolution or significant improvement of signs and symptoms of the index infection such that no further antibacterial therapy, drainage, or surgical intervention was necessary. Indeterminate response are where study data were not available for evaluation of efficacy for any reason, including patient lost to follow-up or assessment not undertaken such that a determination of clinical response could not be made, dDeath where cIAI was clearly noncontributory or circumstances that precluded classification as a cure or failure.
Time Frame TOC: 28 to 35 days after start of study drug
Hide Outcome Measure Data
Hide Analysis Population Description
The MITT analysis set included all randomized patients who met the disease definition of cIAI and who received any amount of study drug.
Arm/Group Title CAZ-AVI + Metronidazole Meropenem
Hide Arm/Group Description:
CAZ (2000mg)/AVI (500mg): IV treatment
1000 mg: IV treatment
Overall Number of Participants Analyzed 520 523
Measure Type: Number
Unit of Measure: Participants
Clinical cure 429 444
Clinical failure 47 39
Indeterminate 44 40
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection CAZ-AVI + Metronidazole, Meropenem
Comments The co-primary objective of this study (ROW agreed) was to determine the noninferiority in the clinical cure rate for CAZ-AVI compared to that for Meropenem at TOC in the MITT in adult subjects with cIAI.
Type of Statistical Test Non-Inferiority or Equivalence
Comments Non-inferiority was determined by comparing the lower limit of the 95% confidence interval for risk difference (corresponding to a 97.5% 1-sided lower bound) to the non-inferiority marging of -12.5%
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value -2.4
Confidence Interval (2-Sided) 95%
-6.90 to 2.10
Estimation Comments [Not Specified]
3.Primary Outcome
Title Clinical Response at the TOC Visit in the Clinically Evaulable (CE) Analysis Set (Co-primary Outcome for Rest of World [ROW]).
Hide Description The number of patients meeting the cure criteria: complete resolution or significant improvement of signs and symptoms of the index infection such that no further antibacterial therapy, drainage, or surgical intervention was necessary.
Time Frame TOC: 28 to 35 days after start of study drug
Hide Outcome Measure Data
Hide Analysis Population Description
The CE analysis set included all patients who met the disease definition of cIAI and met the stringent criteria for clinical evaluation described in the protocol regarding dosing, concomitant medication, evaluation, etc.
Arm/Group Title CAZ-AVI + Metronidazole Meropenem
Hide Arm/Group Description:
CAZ (2000mg)/AVI (500mg): IV treatment
1000 mg: IV treatment
Overall Number of Participants Analyzed 410 416
Measure Type: Number
Unit of Measure: Participants
Clinical cure 376 385
Clinical failure 34 31
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection CAZ-AVI + Metronidazole, Meropenem
Comments The co-primary objective of this study (ROW agreed) was to determine the noninferiority in the clinical cure rate for CAZ-AVI compared to that for Meropenem at TOC in the CE in adult subjects with cIAI.
Type of Statistical Test Non-Inferiority or Equivalence
Comments Non-inferiority was determined by comparing the lower limit of the 95% confidence interval for risk difference (corresponding to a 97.5% 1-sided lower bound) to the non-inferiority marging of -12.5%
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value -0.8
Confidence Interval (2-Sided) 95%
-4.61 to 2.89
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Clinical Cure at TOC in the Microbiologically Evaluable Analysis Set
Hide Description The number of patients meeting the cure criteria: complete resolution or significant improvement of signs and symptoms of the index infection such that no further antibacterial therapy, drainage, or surgical intervention was necessary.
Time Frame TOC: 28 to 35 days after start of study drug
Hide Outcome Measure Data
Hide Analysis Population Description
ME analysis set defined as all patients included in the CE set with at least 1 Gram negative, aerobic, susceptible pathogen in the initial/prestudy culture.
Arm/Group Title CAZ-AVI + Metronidazole Meropenem
Hide Arm/Group Description:
CAZ (2000mg)/AVI (500mg): IV treatment
1000 mg: IV treatment
Overall Number of Participants Analyzed 265 287
Measure Type: Number
Unit of Measure: Participants
Clinical cure 244 272
Clinical failure 21 15
5.Secondary Outcome
Title Clinical Cure at TOC in the Extended Microbiologically Evaluable Analysis Set
Hide Description The number of patients meeting the cure criteria: complete resolution or significant improvement of signs and symptoms of the index infection such that no further antibacterial therapy, drainage, or surgical intervention was necessary.
Time Frame TOC: 28 to 35 days after start of study drug
Hide Outcome Measure Data
Hide Analysis Population Description
Extended ME analysis set defined as all patients included in the CE set with at least 1 Gram negative, aerobic, pathogen in the initial/prestudy culture, regardless of susceptibility.
Arm/Group Title CAZ-AVI + Metronidazole Meropenem
Hide Arm/Group Description:
CAZ (2000mg)/AVI (500mg): IV treatment
1000 mg: IV treatment
Overall Number of Participants Analyzed 270 294
Measure Type: Number
Unit of Measure: Participants
Clinical cure 248 278
Clinical failure 22 16
6.Secondary Outcome
Title Clinical Response by Visit in the Primary Population: Microbiologically Modified Intent-to-Treat (mMITT)
Hide Description Complete resolution or significant improvement of signs and symptoms of the index infection such that no further antibacterial therapy, drainage, or surgical intervention was necessary. Indeterminate response are where study data were not available for evaluation of efficacy for any reason, including patient lost to follow-up or assessment not undertaken such that a determination of clinical response could not be made, dDeath where cIAI was clearly noncontributory or circumstances that precluded classification as a cure or failure.
Time Frame EOT: within 24 hours after last dose of study drug. TOC: 28 to 35 days after start of study drug. LFU: 42 to 49 days after start of study drug
Hide Outcome Measure Data
Hide Analysis Population Description
The mMITT analysis set included all randomized patients who met the disease definition of cIAI and had at least 1 etiologic pathogen identified at study entry (regardless of isolate susceptibilities). Patients with a bacterial species typically not expected to respond to both study drugs were excluded.
Arm/Group Title CAZ-AVI + Metronidazole (EOT) Meropenem (EOT) CAZ-AVI + Metronidazole (TOC) Meropenem (TOC) CAZ-AVI + Metronidazole (LFU) Meropenem (LFU)
Hide Arm/Group Description:
EOT - within 24 hours of last dose of study drug
EOT - within 24 hours of last dose of study drug
TOC - 28 to 35 days after start of study drug
TOC - 28 to 35 days after start of study drug
LFU - 42 to 49 days after start of study drug
LFU - 42 to 49 days after start of study drug
Overall Number of Participants Analyzed 413 410 413 410 413 410
Measure Type: Number
Unit of Measure: Participants
Clinical cure 361 379 337 349 340 347
Clinical failure 30 19 37 30 38 31
Indeterminate 22 12 39 31 35 32
7.Secondary Outcome
Title Per-patient Microbiological Response in the Microbiologically Modified Intent- To-Treat Analysis Set
Hide Description Microbiological responses as per the protocoled criteria: responses other than "indeterminate" were classified as "favorable" or "unfavorable." Favorable microbiological response assessments included "eradication" and "presumed eradication." Unfavorable microbiological response assessments included "persistence," "persistence with increasing minimum inhibitory concentration (MIC)," and "presumed persistence." Indeterminate microbiologic response assessments included cases where the clinical response was changed to indeterminate due to a surgical review panel (SRP) assessment of inadequate source control (ie, circumstances that preclude classification as eradication, presumed eradication, persistence, persistence with increasing MIC, and presumed persistence).
Time Frame EOT: within 24 hours after last dose of study drug. TOC: 28 to 35 days after start of study drug. LFU 42 to 49 days after start of study drug
Hide Outcome Measure Data
Hide Analysis Population Description
The mMITT analysis set included all randomized patients who met the disease definition of cIAI and had at least 1 etiologic pathogen identified at study entry (regardless of isolate susceptibilities). Patients with a bacterial species typically not expected to respond to both study drugs were excluded.
Arm/Group Title CAZ-AVI + Metronidazole (EOT) Meropenem (EOT) CAZ-AVI + Metronidazole (TOC) Meropenem (TOC) CAZ-AVI + Metronidazole (LFU) Meropenem (LFU)
Hide Arm/Group Description:
EOT - within 24 hours after last dose of study drug
EOT - within 24 hours after last dose of study drug
TOC - 28 to 35 days after start of study drug
TOC - 28 to 35 days after start of study drug
LFU - 42 to 49 days after start of study drug
LFU - 42 to 49 days after start of study drug
Overall Number of Participants Analyzed 413 410 413 410 413 410
Measure Type: Number
Unit of Measure: Participants
Favourable response 362 379 337 349 340 347
Unfavourable response 30 19 37 31 38 32
Indeterminate 21 12 39 30 35 31
8.Secondary Outcome
Title Per-pathogen Microbiological Response at TOC in the Microbiologically Modified Intent-To-Treat Analysis Set.
Hide Description The number of patients with a favorable per-pathogen microbiological response: favourable microbiological response includes: Eradication Absence of causative pathogen from specimens at the site of infection. Presumed eradication where, repeat cultures were not performed/clinically indicated in a patient who had a clinical response of cure.
Time Frame TOC: 28 to 35 days after start of study drug.
Hide Outcome Measure Data
Hide Analysis Population Description
The mMITT analysis set included all randomized patients who met the disease definition of cIAI and had at least 1 etiologic pathogen identified at study entry (regardless of isolate susceptibilities). Patients with a bacterial species typically not expected to respond to both study drugs were excluded.
Arm/Group Title CAZ-AVI + Metronidazole Meropenem CAZ-AVI + Metronidazole (Denominator) Meropenem (Denominator)
Hide Arm/Group Description:
CAZ (2000mg)/AVI (500mg): IV treatment Number of favourable responses
1000 mg: IV treatment. Number of favourable responses
Total number of patiets with each pathogen at baseline (summary only shows pathogens where N>/=10)
Number of patients with pathogen at baseline
Overall Number of Participants Analyzed 413 410 413 410
Measure Type: Number
Unit of Measure: Participants
Citrobacter freundii complex 14 9 18 12
Enterobacter aerogenes 4 5 5 5
Enterobacter cloacae 11 16 13 19
Escherichia coli 218 249 271 285
Klebsiella oxytoca 14 12 18 15
Klebsiella pneumoniae 40 37 51 49
Proteus mirabilis 5 7 8 9
Pseudomonas aeruginosa 30 34 35 36
Enterococcus avium 8 10 8 15
Enterococcus faecalis 22 23 31 28
Enterococcus faecium 13 18 16 22
Staphylococcus aureus 17 14 18 14
Streptococcus anginosus group 59 50 72 61
Streptococcus bovis group 2 6 3 7
Streptococcus mitis group 10 9 15 11
Bacteroides fragilis 45 38 52 47
Bacteroides ovatus 17 17 22 20
Bacteroides stercoris 9 1 10 1
Bacteroides thetaiotaomicron 18 21 22 25
Bacteroides uniformis 4 6 7 7
Bacteroides vulgatus 6 6 8 9
Clostridium perfringens 7 4 10 4
Eggerthella lenta 5 7 5 8
Parabacteroides distasonis 13 12 16 13
Parvimonas micra 7 8 7 10
9.Secondary Outcome
Title Clinical Response by Pathogen at TOC for Patients Infected With Ceftazidime-resistant Pathogens in Microbiological Modified Intent to Treat Analysis Set
Hide Description Complete resolution or significant improvement of signs and symptoms of the index infection such that no further antibacterial therapy, drainage, or surgical intervention was necessary.
Time Frame Test of Cure: 28 to 35 days after start of study drug
Hide Outcome Measure Data
Hide Analysis Population Description
The mMITT analysis set included all randomized patients who met the disease definition of cIAI and had at least 1 etiologic pathogen identified at study entry (regardless of isolate susceptibilities). Patients with a bacterial species typically not expected to respond to both study drugs were excluded.
Arm/Group Title CAZ-AVI + Metronidazole Meropenem CAZ-AVI + Metronidazole (Denominator) Meropenem (Denominator)
Hide Arm/Group Description:
CAZ (2000mg)/AVI (500mg): IV treatment
1000 mg: IV treatment
Number of patients with pathogen at baseline
Number of patients with pathogen at baseline
Overall Number of Participants Analyzed 413 410 413 410
Measure Type: Number
Unit of Measure: Participants
All 39 55 47 64
Citrobacter freundii complex 1 2 1 2
Enterobacter aerogenes 0 1 0 1
Enterobacter cloacae 2 7 3 7
Escherichia coli 19 31 24 37
Klebsiella pneumoniae 10 9 13 13
Morganella morganii 1 1 2 1
Proteus mirabilis 2 3 2 3
Serratia marcescens 1 0 1 0
Alcaligenes faecalis 1 2 1 2
Comamonas testosteroni 1 0 1 0
Pseudomonas aeruginosa 2 4 2 4
10.Secondary Outcome
Title Favorable Per-pathogen Microbiological Response for Patients Infected With Ceftazidime-resistant Pathogens in mMITT Analysis Set
Hide Description The number of patients with a favorable per-pathogen microbiological response: favourable microbiological response includes: Eradication Absence of causative pathogen from specimens at the site of infection. Presumed eradication where, repeat cultures were not performed/clinically indicated in a patient who had a clinical response of cure.
Time Frame TOC: 28 to 35 days after start of study drug
Hide Outcome Measure Data
Hide Analysis Population Description
The mMITT analysis set included all randomized patients who met the disease definition of cIAI and had at least 1 etiologic pathogen identified at study entry (regardless of isolate susceptibilities). Patients with a bacterial species typically not expected to respond to both study drugs were excluded.
Arm/Group Title CAZ-AVI + Metronidazole Meropenem CAZ-AVI + Metronidazole (Denominator) Meropenem (Denominator)
Hide Arm/Group Description:
CAZ (2000mg)/AVI (500mg): IV treatment
1000 mg: IV treatment
Number of patients with pathogen at baseline
Number of patients with pathogen at baseline
Overall Number of Participants Analyzed 48 64 48 64
Measure Type: Number
Unit of Measure: Participants
Citrobacter freundii complex 1 2 2 2
Enterobacter aerogenes 0 1 0 1
Enterobacter cloacae 2 7 3 7
Escherichia coli 19 31 24 37
Klebsiella pneumoniae 10 9 13 13
Morganella morganii 1 1 2 1
Proteus mirabilis 2 3 2 3
Serratia marcescens 1 0 1 0
Alcaligenes faecalis 1 2 1 2
Comamonas testosteroni 1 0 1 0
Pseudomonas aeruginosa 2 4 2 4
11.Secondary Outcome
Title Per-patient Microbiological Response at TOC for Patients Infected With Ceftazidime-resistant Pathogens in mMITT Analysis Set
Hide Description Microbiological responses other than "indeterminate" were classified as "favorable" or "unfavorable." Favorable microbiological response assessments included "eradication" and "presumed eradication." Unfavorable microbiological response assessments included "persistence," "persistence with increasing minimum inhibitory concentration (MIC)," and "presumed persistence." Indeterminate microbiologic response assessments included cases where the clinical response was changed to indeterminate due to an SRP assessment of inadequate source control (ie, circumstances that preclude classification as eradication, presumed eradication, persistence, persistence with increasing MIC, and presumed persistence).
Time Frame Test of Cure: 28 to 35 days after start of study drug
Hide Outcome Measure Data
Hide Analysis Population Description
The mMITT analysis set included all randomized patients who met the disease definition of cIAI and had at least 1 etiologic pathogen identified at study entry (regardless of isolate susceptibilities). Patients with a bacterial species typically not expected to respond to both study drugs were excluded.
Arm/Group Title CAZ-AVI + Metronidazole Meropenem
Hide Arm/Group Description:
CAZ (2000mg)/AVI (500mg): IV treatment
1000 mg: IV treatment
Overall Number of Participants Analyzed 48 64
Measure Type: Number
Unit of Measure: Participants
Favourable 39 55
Unfavourable 7 1
indeterminate 2 8
12.Secondary Outcome
Title Number of Patients Afebrile at Last Observation in the Clinically Evaluable Analysis Set for Patients Who Have Fever at Study Entry
Hide Description Time to first defervescence was calculated for patients with a fever (>38ºC) at baseline. Defervescence (≤37.8ºC) was defined as the absence of fever based on the highest temperature recorded on each study day.
Time Frame Test of Cure: 1 to 14 days after start of study drug
Hide Outcome Measure Data
Hide Analysis Population Description
Clinically evaluable (CE) with fever, defined as >38ºC at study entry.
Arm/Group Title CAZ-AVI + Metronidazole Meropenem
Hide Arm/Group Description:
CAZ (2000mg)/AVI (500mg): IV treatment
1000 mg: IV treatment
Overall Number of Participants Analyzed 84 78
Measure Type: Number
Unit of Measure: Participants
84 72
13.Secondary Outcome
Title Plasma Concentrations for Ceftazidime and Avibactam
Hide Description Blood samples were taken from all patients on Day 3 for the pharmacokinetic evaluation of ceftazidime and avibactam plasma concentrations
Time Frame Anytime within 15 minutes prior to or after stopping study drug, anytime between 30 and 90 minutes after stopping study drug, anytime between 300 minutes and 360 minutes after stopping study drug
Hide Outcome Measure Data
Hide Analysis Population Description
PK analysis set
Arm/Group Title CAZ (1) AVI (1) CAZ (2) AVI (2) CAZ (3) AVI (3)
Hide Arm/Group Description:
30 mins before/after dose
30 min before/after dose
30-90 mins after dose
30-90 mins after dose
300-360 mins after dose
300-360 mins after dose
Overall Number of Participants Analyzed 486 493 484 489 481 484
Geometric Mean (Full Range)
Unit of Measure: (NG/ML)
50823.0
(171 to 3110000)
9229.4
(13 to 693000)
40053.1
(155 to 235000)
7163.9
(15 to 46800)
10967.6
(159 to 151000)
1690.7
(14 to 30800)
Time Frame Adverse event data were collected from the screening/consent visit until the late follow-up visit (ie Day -1/0 to Day 42).
Adverse Event Reporting Description AEs spontaneously reported by the patient or care provider or reported in response to the open question from the study center personnel, or revealed by observation were to be collected and recorded in the eCRF.
 
Arm/Group Title CAZ-AVI + Metronidazole Meropenem
Hide Arm/Group Description CAZ (2000mg)/AVI (500mg): IV treatment. 1000 mg: IV treatment
All-Cause Mortality
CAZ-AVI + Metronidazole Meropenem
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Hide Serious Adverse Events
CAZ-AVI + Metronidazole Meropenem
Affected / at Risk (%) Affected / at Risk (%)
Total   17/529 (3.21%)   15/529 (2.84%) 
Blood and lymphatic system disorders     
Bone marrow failure † 1  0/529 (0.00%)  1/529 (0.19%) 
Disseminated intravascular coagulation † 1  1/529 (0.19%)  0/529 (0.00%) 
Cardiac disorders     
Myocardial infarction † 1  1/529 (0.19%)  2/529 (0.38%) 
Cardiac failure † 1  2/529 (0.38%)  1/529 (0.19%) 
Acute myocardial infarction † 1  1/529 (0.19%)  1/529 (0.19%) 
Atrial fibrillation † 1  0/529 (0.00%)  1/529 (0.19%) 
Cardiac failure congestive † 1  1/529 (0.19%)  1/529 (0.19%) 
Cardio-respiratory arrest † 1  0/529 (0.00%)  1/529 (0.19%) 
Left ventricular failure † 1  1/529 (0.19%)  0/529 (0.00%) 
Right ventricular failure † 1  1/529 (0.19%)  0/529 (0.00%) 
Gastrointestinal disorders     
Abdominal pain † 1  2/529 (0.38%)  0/529 (0.00%) 
Colonic fistula † 1  0/529 (0.00%)  1/529 (0.19%) 
Duodenal ulcer haemorrhage † 1  1/529 (0.19%)  0/529 (0.00%) 
Gastrointestinal haemorrhage † 1  1/529 (0.19%)  0/529 (0.00%) 
Gastrointestinal hypomotility † 1  1/529 (0.19%)  0/529 (0.00%) 
Ileal perforation † 1  1/529 (0.19%)  0/529 (0.00%) 
Ileus † 1  1/529 (0.19%)  0/529 (0.00%) 
Intestinal obstruction † 1  0/529 (0.00%)  1/529 (0.19%) 
Large intestine perforation † 1  1/529 (0.19%)  0/529 (0.00%) 
Localised intraabdominal fluid collection † 1  1/529 (0.19%)  0/529 (0.00%) 
Rectal haemorrhage † 1  0/529 (0.00%)  1/529 (0.19%) 
Small intestine perforation † 1  1/529 (0.19%)  0/529 (0.00%) 
Subileus † 1  0/529 (0.00%)  1/529 (0.19%) 
Upper gastrointestinal haemorrhage † 1  0/529 (0.00%)  1/529 (0.19%) 
Volvulus † 1  0/529 (0.00%)  1/529 (0.19%) 
Small intestinal obstruction † 1  1/529 (0.19%)  1/529 (0.19%) 
General disorders     
Multi-organ failure † 1  1/529 (0.19%)  0/529 (0.00%) 
Sudden death † 1  1/529 (0.19%)  1/529 (0.19%) 
Hepatobiliary disorders     
Bile duct obstruction † 1  1/529 (0.19%)  1/529 (0.19%) 
Biloma † 1  1/529 (0.19%)  0/529 (0.00%) 
Immune system disorders     
Hypersensitivity † 1  1/529 (0.19%)  0/529 (0.00%) 
Infections and infestations     
Abdominal abscess † 1  0/529 (0.00%)  2/529 (0.38%) 
Bronchopneumonia † 1  2/529 (0.38%)  2/529 (0.38%) 
Candida sepsis † 1  2/529 (0.38%)  0/529 (0.00%) 
Colonic abscess † 1  0/529 (0.00%)  1/529 (0.19%) 
Diverticulitis † 1  1/529 (0.19%)  0/529 (0.00%) 
Empyema † 1  1/529 (0.19%)  0/529 (0.00%) 
Enterococcal bacteraemia † 1  1/529 (0.19%)  1/529 (0.19%) 
Pneumonia † 1  1/529 (0.19%)  1/529 (0.19%) 
Sepsis † 1  0/529 (0.00%)  1/529 (0.19%) 
Septic enceohalopathy † 1  1/529 (0.19%)  0/529 (0.00%) 
Septic shock † 1  0/529 (0.00%)  1/529 (0.19%) 
Systematic candida † 1  0/529 (0.00%)  1/529 (0.19%) 
Injury, poisoning and procedural complications     
Gastrointestinal stoma necrosis † 1  2/529 (0.38%)  0/529 (0.00%) 
Abdominal wound dehiscence † 1  1/529 (0.19%)  1/529 (0.19%) 
Anastomotic leak † 1  1/529 (0.19%)  0/529 (0.00%) 
Gastrointestinal stoma complication † 1  1/529 (0.19%)  1/529 (0.19%) 
Laceration † 1  0/529 (0.00%)  1/529 (0.19%) 
Pneumothorax traumatic † 1  1/529 (0.19%)  0/529 (0.00%) 
Post procedural bile leak † 1  0/529 (0.00%)  1/529 (0.19%) 
Postoperative wound complication † 1  1/529 (0.19%)  0/529 (0.00%) 
Procedural pain † 1  1/529 (0.19%)  0/529 (0.00%) 
Suture related complication † 1  1/529 (0.19%)  0/529 (0.00%) 
Wound dehiscence † 1  0/529 (0.00%)  1/529 (0.19%) 
Wound evisceration † 1  0/529 (0.00%)  1/529 (0.19%) 
Investigations     
Transaminases increased † 1  0/529 (0.00%)  2/529 (0.38%) 
Metabolism and nutrition disorders     
Hypoglycaemia † 1  0/529 (0.00%)  2/529 (0.38%) 
Dehydration † 1  1/529 (0.19%)  0/529 (0.00%) 
Musculoskeletal and connective tissue disorders     
Critical illness myopathy † 1  0/529 (0.00%)  1/529 (0.19%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Adenocarcinoma gastric † 1  0/529 (0.00%)  1/529 (0.19%) 
Nervous system disorders     
Ischaemic stroke † 1  0/529 (0.00%)  1/529 (0.19%) 
Polyneuropathy † 1  0/529 (0.00%)  1/529 (0.19%) 
Psychiatric disorders     
Delirium tremens † 1  1/529 (0.19%)  0/529 (0.00%) 
Renal and urinary disorders     
Renal failure acute † 1  5/529 (0.95%)  0/529 (0.00%) 
Renal failure † 1  1/529 (0.19%)  0/529 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Respiratory failure † 1  3/529 (0.57%)  3/529 (0.57%) 
Pulmonary embolism † 1  3/529 (0.57%)  1/529 (0.19%) 
Atelectasis † 1  0/529 (0.00%)  1/529 (0.19%) 
Chronic obstructive pulmonary disease † 1  0/529 (0.00%)  1/529 (0.19%) 
Pleural effusion † 1  1/529 (0.19%)  1/529 (0.19%) 
Pneumothorax † 1  0/529 (0.00%)  1/529 (0.19%) 
Pulmonary congestion † 1  0/529 (0.00%)  1/529 (0.19%) 
Respiratory distress † 1  1/529 (0.19%)  1/529 (0.19%) 
Skin and subcutaneous tissue disorders     
Drug eruption † 1  0/529 (0.00%)  1/529 (0.19%) 
Vascular disorders     
Shock † 1  1/529 (0.19%)  0/529 (0.00%) 
†
Indicates events were collected by systematic assessment
1
Term from vocabulary, (MedDRA)
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 2%
CAZ-AVI + Metronidazole Meropenem
Affected / at Risk (%) Affected / at Risk (%)
Total   184/529 (34.78%)   152/529 (28.73%) 
Blood and lymphatic system disorders     
Anaemia † 1  11/529 (2.08%)  9/529 (1.70%) 
Gastrointestinal disorders     
Diarrhoea † 1  40/529 (7.56%)  17/529 (3.21%) 
Nausea † 1  36/529 (6.81%)  24/529 (4.54%) 
Vomiting † 1  24/529 (4.54%)  10/529 (1.89%) 
Constipation † 1  8/529 (1.51%)  20/529 (3.78%) 
Abdominal distension † 1  10/529 (1.89%)  11/529 (2.08%) 
General disorders     
Pyrexia † 1  24/529 (4.54%)  24/529 (4.54%) 
Asthenia † 1  10/529 (1.89%)  12/529 (2.27%) 
Infections and infestations     
Wound infection † 1  13/529 (2.46%)  11/529 (2.08%) 
Nervous system disorders     
Headache † 1  15/529 (2.84%)  9/529 (1.70%) 
Respiratory, thoracic and mediastinal disorders     
Cough † 1  11/529 (2.08%)  13/529 (2.46%) 
Vascular disorders     
Hypertension † 1  15/529 (2.84%)  24/529 (4.54%) 
Hypotension † 1  12/529 (2.27%)  12/529 (2.27%) 
Phlebitis † 1  10/529 (1.89%)  11/529 (2.08%) 
†
Indicates events were collected by systematic assessment
1
Term from vocabulary, (MedDRA)
This summary describes data collected from two identical CSPs (D4280C00001 and D4280C00005). With agreement from the EMA and the FDA the data have been combined into a single study database.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The PI shall not publish results until the earliest of (i) date of the 1st study publication (joint between PI, sponsor and study sites) (ii) 18 months after study completion, or (iii) sponsor notification that no multi-center publication is to be made. The PI submits the publication for review 60 days before submission. Sponsor may embargo for a further 90 days to protect IP rights. Sponsor may request removal of confidential and/or proprietry information.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Paul Newell, Medical Science Director
Organization: AstraZeneca
Phone: +44 1625 515727
EMail: paul.newell@astrazeneca.com
Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT01499290    
Obsolete Identifiers: NCT01500239
Other Study ID Numbers: D4280C00001
2011-003893-97
First Submitted: December 19, 2011
First Posted: December 26, 2011
Results First Submitted: November 6, 2015
Results First Posted: March 1, 2016
Last Update Posted: September 6, 2017