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Trial record 9 of 29 for:    ceftazidime AND avibactam

Compare Ceftazidime-Avibactam + Metronidazole vs Meropenem for Hospitalized Adults With Complicated Intra-Abd Infections (RECLAIM3)

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ClinicalTrials.gov Identifier: NCT01726023
Recruitment Status : Completed
First Posted : November 14, 2012
Results First Posted : April 14, 2016
Last Update Posted : September 6, 2017
Sponsor:
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: Ceftazidime-avibactam
Drug: metronidazole
Drug: Meropenem
Enrollment 486
Recruitment Details Overall, 486 patients were enrolled from 43 centers in 3 countries in this study. The first patient was enrolled on 14 January 2013 and the last patient last visit was on 14 March 2015.
Pre-assignment Details Of 486 enrolled patients, 42 did not meet the eligibility criteria. A further two patients were not randomized due to withdrawn consent, and one patient was not randomized due to unavailability of study drug.
Arm/Group Title Ceftazidime-Avibactam Plus Metronidazole Meropenem
Hide Arm/Group Description Ceftazidime-Avibactam powder for concentrate for solution for infusion 2000 mg/500 mg Plus Metronidazole 500mg/100ml solution for infusion Meropenem powder for solution for infusion 1000mg
Period Title: Overall Study
Started 219 222
Completed 190 196
Not Completed 29 26
Reason Not Completed
Death             1             1
Lost to Follow-up             5             10
Other Eligibility criteria             7             7
Withdrawal by Subject             16             8
Arm/Group Title Ceftazidime-Avibactam Plus Metronidazole Meropenem Total
Hide Arm/Group Description Ceftazidime-Avibactam powder for concentrate for solution for infusion 2000 mg/500 mg Plus Metronidazole 500mg/100ml solution for infusion Meropenem powder for solution for infusion 1000mg Total of all reporting groups
Overall Number of Baseline Participants 214 217 431
Hide Baseline Analysis Population Description
Baseline analysis population is MITT ; Randomized patients who received any amount of study therapy, excluding patients who received both study therapies. 9 patients were randomized but not treated, and one patient received doses of both treatments.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 214 participants 217 participants 431 participants
48.5  (16.83) 48.5  (17.43) 48.5  (17.11)
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 214 participants 217 participants 431 participants
18-45 Years 89 96 185
46-64 Years 85 72 157
65-74 Years 28 30 58
75-90 Years 12 19 31
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 214 participants 217 participants 431 participants
Female
73
  34.1%
64
  29.5%
137
  31.8%
Male
141
  65.9%
153
  70.5%
294
  68.2%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Asian Number Analyzed 214 participants 217 participants 431 participants
214 217 431
1.Primary Outcome
Title The Proportion of Patients With Clinical Cure at the Test of Cure (TOC) Visit in the Clinically Evaluable (CE) Analysis Set.
Hide Description The proportion 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 At the test of cure visit (Day 28 to35)
Hide Outcome Measure Data
Hide Analysis Population Description
The clinically evaluable (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 Ceftazidime-Avibactam Plus Metronidazole Meropenem
Hide Arm/Group Description:
Ceftazidime-Avibactam powder for concentrate for solution for infusion 2000 mg/500 mg Plus Metronidazole 500mg/100ml solution for infusion
Meropenem powder for solution for infusion 1000mg
Overall Number of Participants Analyzed 177 184
Measure Type: Number
Unit of Measure: Number of patients
Clinical cure 166 173
Clinical failure 11 11
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ceftazidime-Avibactam Plus Metronidazole, Meropenem
Comments The Primary objective of this study was to assess the non inferiority (based on a 12.5% margin) of CAZ AVI plus metronidazole compared to meropenem alone with respect to clinical cure at the TOC visit in patients who were CE.
Type of Statistical Test Non-Inferiority or Equivalence
Comments The non-inferiority would be concluded if the lower limit of the 95% confidence interval (CI; corresponding to a 97.5% 1 sided lower bound) was greater than -12.5% for the primary outcome variable.
Statistical Test of Hypothesis P-Value <0.001
Comments P-value for 1-sided test at test of cure (TOC) with a -12.5% non-inferiority margin, i.e. H0: diff ≤ -12.5%.
Method % Risk Difference (RD)
Comments RD is CAZ AVI clinical cure rate minus Meropenem clinical cure rate. The CI was calculated by Miettinen and Nurminen method without adjustment.
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value -0.20
Confidence Interval (2-Sided) 95%
-5.53 to 4.97
Estimation Comments units for RD are %
2.Secondary Outcome
Title The Proportion of Patients With Clinical Cure at the End of Treatment (EOT) Visit in the Microbiologically Evaluable (ME) Analysis Set.
Hide Description The proportion 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 At the end of treatment (EOT) (within 24 hours after last IV dose)
Hide Outcome Measure Data
Hide Analysis Population Description
Microbiologically evaluable (ME) analysis set defined as all patients included in the clinically evaluable (CE) set with at least 1 Gram-negative aerobic pathogen in the initial/prestudy culture that was susceptible to both treatment groups.
Arm/Group Title Ceftazidime-Avibactam Plus Metronidazole Meropenem
Hide Arm/Group Description:
Ceftazidime-Avibactam powder for concentrate for solution for infusion 2000 mg/500 mg Plus Metronidazole 500mg/100ml solution for infusion
Meropenem powder for solution for infusion 1000mg
Overall Number of Participants Analyzed 106 118
Measure Type: Number
Unit of Measure: Number of patients
Clinical cure 103 113
Clinical failure 3 5
3.Secondary Outcome
Title The Proportion of Patients With Clinical Cure at the Test of Cure (TOC) Visit in the Microbiologically Evaluable (ME) Analysis Set.
Hide Description The proportion 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 At the test of cure (TOC) (Day 28 to 35)
Hide Outcome Measure Data
Hide Analysis Population Description
Microbiologically evaluable (ME) analysis set defined as all patients included in the clinically evaluable (CE) set with at least 1 Gram-negative aerobic pathogen in the initial/prestudy culture that was susceptible to both treatment groups.
Arm/Group Title Ceftazidime-Avibactam Plus Metronidazole Meropenem
Hide Arm/Group Description:
Ceftazidime-Avibactam powder for concentrate for solution for infusion 2000 mg/500 mg Plus Metronidazole 500mg/100ml solution for infusion
Meropenem powder for solution for infusion 1000mg
Overall Number of Participants Analyzed 99 113
Measure Type: Number
Unit of Measure: Number of patients
Clinical cure 92 107
Clinical failure 7 6
4.Secondary Outcome
Title The Proportion of Patients With Clinical Cure at the Late Follow up (LFU) Visit in the Microbiologically Evaluable (ME) Analysis Set.
Hide Description The proportion 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 At the late follow up (LFU) (Day 42 to 49)
Hide Outcome Measure Data
Hide Analysis Population Description
Microbiologically evaluable (ME) analysis set defined as all patients included in the clinically evaluable (CE) set with at least 1 Gram-negative aerobic pathogen in the initial/prestudy culture that was susceptible to both treatment groups.
Arm/Group Title Ceftazidime-Avibactam Plus Metronidazole Meropenem
Hide Arm/Group Description:
Ceftazidime-Avibactam powder for concentrate for solution for infusion 2000 mg/500 mg Plus Metronidazole 500mg/100ml solution for infusion
Meropenem powder for solution for infusion 1000mg
Overall Number of Participants Analyzed 96 106
Measure Type: Number
Unit of Measure: Number of patients
Clinical cure 89 100
Clinical failure 7 6
5.Secondary Outcome
Title The Proportion of Patients With Clinical Cure at the End of Treatment (EOT) Visit in the Extended Microbiologically Evaluable (ME) Analysis Set.
Hide Description The proportion 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 At the end of treatment (EOT) (within 24 hours after last IV dose)
Hide Outcome Measure Data
Hide Analysis Population Description
Extended microbiologically evaluable (ME) analysis set defined as all patients included in the clinically evaluable (CE) set with at least 1 Gram-negative aerobic pathogen in the initial/prestudy culture regardless of susceptibility.
Arm/Group Title Ceftazidime-Avibactam Plus Metronidazole Meropenem
Hide Arm/Group Description:
Ceftazidime-Avibactam powder for concentrate for solution for infusion 2000 mg/500 mg Plus Metronidazole 500mg/100ml solution for infusion
Meropenem powder for solution for infusion 1000mg
Overall Number of Participants Analyzed 107 125
Measure Type: Number
Unit of Measure: Number of patients
Clinical cure 104 120
Clinical failure 3 5
6.Secondary Outcome
Title The Proportion of Patients With Clinical Cure at the Test of Cure (TOC) Visit in the Extended Microbiologically Evaluable (ME) Analysis Set.
Hide Description The proportion 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 At the test of cure (TOC) (Day 28 to 35)
Hide Outcome Measure Data
Hide Analysis Population Description
Extended microbiologically evaluable (ME) analysis set defined as all patients included in the clinically evaluable (CE) set with at least 1 Gram-negative aerobic pathogen in the initial/prestudy culture regardless of susceptibility.
Arm/Group Title Ceftazidime-Avibactam Plus Metronidazole Meropenem
Hide Arm/Group Description:
Ceftazidime-Avibactam powder for concentrate for solution for infusion 2000 mg/500 mg Plus Metronidazole 500mg/100ml solution for infusion
Meropenem powder for solution for infusion 1000mg
Overall Number of Participants Analyzed 100 119
Measure Type: Number
Unit of Measure: Number of patients
Clinical cure 93 113
Clinical failure 7 6
7.Secondary Outcome
Title The Proportion of Patients With Clinical Cure at the Late Follow up (LFU) Visit in the Extended Microbiologically Evaluable (ME) Analysis Set.
Hide Description The proportion 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 At the late follow up (LFU) (Day 42 to 49)
Hide Outcome Measure Data
Hide Analysis Population Description
Extended microbiologically evaluable (ME) analysis set defined as all patients included in the clinically evaluable (CE) set with at least 1 Gram-negative aerobic pathogen in the initial/prestudy culture regardless of susceptibility.
Arm/Group Title Ceftazidime-Avibactam Plus Metronidazole Meropenem
Hide Arm/Group Description:
Ceftazidime-Avibactam powder for concentrate for solution for infusion 2000 mg/500 mg Plus Metronidazole 500mg/100ml solution for infusion
Meropenem powder for solution for infusion 1000mg
Overall Number of Participants Analyzed 97 112
Measure Type: Number
Unit of Measure: Number of patients
Clinical cure 90 106
Clinical failure 7 6
8.Secondary Outcome
Title The Proportion of Patients With Clinical Cure at the End of Treatment (EOT) Visit in the Microbiological Modified Intent-to-treat (mMITT) Analysis Set.
Hide Description The proportion 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 At the end of treatment (EOT) (within 24 hours after last IV dose)
Hide Outcome Measure Data
Hide Analysis Population Description
The microbiological modified intent-to-treat 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 Ceftazidime-Avibactam Plus Metronidazole Meropenem
Hide Arm/Group Description:
Ceftazidime-Avibactam powder for concentrate for solution for infusion 2000 mg/500 mg Plus Metronidazole 500mg/100ml solution for infusion
Meropenem powder for solution for infusion 1000mg
Overall Number of Participants Analyzed 143 152
Measure Type: Number
Unit of Measure: Number of patients
Clinical cure 126 140
Clinical failure 6 7
Indeterminate 11 5
9.Secondary Outcome
Title The Proportion of Patients With Clinical Cure at the Test of Cure (TOC) Visit in the Microbiological Modified Intent-to-treat (mMITT) Analysis Set.
Hide Description The proportion 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 At the test of cure (TOC) (Day 28 to 35)
Hide Outcome Measure Data
Hide Analysis Population Description
The microbiological modified intent-to-treat 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 Ceftazidime-Avibactam Plus Metronidazole Meropenem
Hide Arm/Group Description:
Ceftazidime-Avibactam powder for concentrate for solution for infusion 2000 mg/500 mg Plus Metronidazole 500mg/100ml solution for infusion
Meropenem powder for solution for infusion 1000mg
Overall Number of Participants Analyzed 143 152
Measure Type: Number
Unit of Measure: Number of patients
Clinical cure 119 135
Clinical failure 10 9
Indeterminate 14 8
10.Secondary Outcome
Title The Proportion of Patients With Clinical Cure at the Late Follow up (LFU) Visit in the Microbiological Modified Intent-to-treat (mMITT) Analysis Set.
Hide Description The proportion 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 At the late follow up (LFU) (Day 42 to 49)
Hide Outcome Measure Data
Hide Analysis Population Description
The microbiological modified intent-to-treat 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 Ceftazidime-Avibactam Plus Metronidazole Meropenem
Hide Arm/Group Description:
Ceftazidime-Avibactam powder for concentrate for solution for infusion 2000 mg/500 mg Plus Metronidazole 500mg/100ml solution for infusion
Meropenem powder for solution for infusion 1000mg
Overall Number of Participants Analyzed 143 152
Measure Type: Number
Unit of Measure: Number of patients
Clinical cure 116 132
Clinical failure 10 9
Indeterminate 17 11
11.Secondary Outcome
Title The Proportion of Patients With Clinical Cure at the End of Treatment (EOT) Visit in the Clinically Evaluable (CE) Analysis Set.
Hide Description The proportion 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 At the end of treatment (EOT) (within 24 hours after last IV dose)
Hide Outcome Measure Data
Hide Analysis Population Description
The clinically evaluable (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 Ceftazidime-Avibactam Plus Metronidazole Meropenem
Hide Arm/Group Description:
Ceftazidime-Avibactam powder for concentrate for solution for infusion 2000 mg/500 mg Plus Metronidazole 500mg/100ml solution for infusion
Meropenem powder for solution for infusion 1000mg
Overall Number of Participants Analyzed 190 196
Measure Type: Number
Unit of Measure: Number of patients
Clinical cure 183 187
Clinical failure 7 9
12.Secondary Outcome
Title The Proportion of Patients With Clinical Cure at the Late Follow up (LFU) Visit in the Clinically Evaluable (CE) Analysis Set.
Hide Description The proportion 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 At late follow up (LFU) visits (Day 42 to 49)
Hide Outcome Measure Data
Hide Analysis Population Description
The clinically evaluable (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 Ceftazidime-Avibactam Plus Metronidazole Meropenem
Hide Arm/Group Description:
Ceftazidime-Avibactam powder for concentrate for solution for infusion 2000 mg/500 mg Plus Metronidazole 500mg/100ml solution for infusion
Meropenem powder for solution for infusion 1000mg
Overall Number of Participants Analyzed 168 179
Measure Type: Number
Unit of Measure: Number of patients
Clinical cure 157 168
Clinical failure 11 11
13.Secondary Outcome
Title The Proportion of Patients With a Favorable Per-patient Microbiological Response at the End of Treatment (EOT) Visit in the Microbiologically Evaluable (ME) Analysis Set.
Hide Description Per-patient "favorable" response indicates that all of the patient's baseline pathogens are "eradicated" or "presumed eradicated".
Time Frame At the end of treatment (EOT) (within 24 hours after last IV dose)
Hide Outcome Measure Data
Hide Analysis Population Description
Microbiologically evaluable (ME) analysis set defined as all patients included in the clinically evaluable (CE) set with at least 1 Gram-negative aerobic pathogen in the initial/prestudy culture that was susceptible to both treatment groups.
Arm/Group Title Ceftazidime-Avibactam Plus Metronidazole Meropenem
Hide Arm/Group Description:
Ceftazidime-Avibactam powder for concentrate for solution for infusion 2000 mg/500 mg Plus Metronidazole 500mg/100ml solution for infusion
Meropenem powder for solution for infusion 1000mg
Overall Number of Participants Analyzed 106 118
Measure Type: Number
Unit of Measure: Number of patients
Favorable 103 113
Unfavorable 3 5
14.Secondary Outcome
Title The Proportion of Patients With a Favorable Per-patient Microbiological Response at the Test of Cure (TOC) Visit in the Microbiologically Evaluable (ME) Analysis Set.
Hide Description Per-patient "favorable" response indicates that all of the patient's baseline pathogens are "eradicated" or "presumed eradicated".
Time Frame At the test of cure (TOC) (Day 28 to 35)
Hide Outcome Measure Data
Hide Analysis Population Description
Microbiologically evaluable (ME) analysis set defined as all patients included in the clinically evaluable (CE) set with at least 1 Gram-negative aerobic pathogen in the initial/prestudy culture that was susceptible to both treatment groups.
Arm/Group Title Ceftazidime-Avibactam Plus Metronidazole Meropenem
Hide Arm/Group Description:
Ceftazidime-Avibactam powder for concentrate for solution for infusion 2000 mg/500 mg Plus Metronidazole 500mg/100ml solution for infusion
Meropenem powder for solution for infusion 1000mg
Overall Number of Participants Analyzed 99 113
Measure Type: Number
Unit of Measure: Number of patients
Favorable 92 107
Unfavorable 7 6
15.Secondary Outcome
Title The Proportion of Patients With a Favorable Per-patient Microbiological Response at the Late Follow up (LFU) Visit in the Microbiologically Evaluable (ME) Analysis Set.
Hide Description Per-patient "favorable" response indicates that all of the patient's baseline pathogens are "eradicated" or "presumed eradicated".
Time Frame At the late follow up (LFU) (Day 42 to 49)
Hide Outcome Measure Data
Hide Analysis Population Description
Microbiologically evaluable (ME) analysis set defined as all patients included in the clinically evaluable (CE) set with at least 1 Gram-negative aerobic pathogen in the initial/prestudy culture that was susceptible to both treatment groups.
Arm/Group Title Ceftazidime-Avibactam Plus Metronidazole Meropenem
Hide Arm/Group Description:
Ceftazidime-Avibactam powder for concentrate for solution for infusion 2000 mg/500 mg Plus Metronidazole 500mg/100ml solution for infusion
Meropenem powder for solution for infusion 1000mg
Overall Number of Participants Analyzed 96 106
Measure Type: Number
Unit of Measure: Number of patients
Favorable 89 100
Unfavorable 7 6
16.Secondary Outcome
Title The Proportion of Patients With a Favorable Per-patient Microbiological Response at the End of Treatment (EOT) Visit in the Extended Microbiologically Evaluable (ME) Analysis Set.
Hide Description Per-patient "favorable" response indicates that all of the patient's baseline pathogens are "eradicated" or "presumed eradicated".
Time Frame At the end of treatment (EOT) (within 24 hours after last IV dose)
Hide Outcome Measure Data
Hide Analysis Population Description
Extended microbiologically evaluable (ME) analysis set defined as all patients included in the clinically evaluable (CE) set with at least 1 Gram-negative aerobic pathogen in the initial/prestudy culture regardless of susceptibility.
Arm/Group Title Ceftazidime-Avibactam Plus Metronidazole Meropenem
Hide Arm/Group Description:
Ceftazidime-Avibactam powder for concentrate for solution for infusion 2000 mg/500 mg Plus Metronidazole 500mg/100ml solution for infusion
Meropenem powder for solution for infusion 1000mg
Overall Number of Participants Analyzed 107 125
Measure Type: Number
Unit of Measure: Number of patients
Favorable 104 120
Unfavorable 3 5
17.Secondary Outcome
Title The Proportion of Patients With a Favorable Per-patient Microbiological Response at the Test of Cure (TOC) Visit in the Extended Microbiologically Evaluable (ME) Analysis Set.
Hide Description Per-patient "favorable" response indicates that all of the patient's baseline pathogens are "eradicated" or "presumed eradicated".
Time Frame At the test of cure (TOC) (Day 28 to 35)
Hide Outcome Measure Data
Hide Analysis Population Description
Extended microbiologically evaluable (ME) analysis set defined as all patients included in the clinically evaluable (CE) set with at least 1 Gram-negative aerobic pathogen in the initial/prestudy culture regardless of susceptibility.
Arm/Group Title Ceftazidime-Avibactam Plus Metronidazole Meropenem
Hide Arm/Group Description:
Ceftazidime-Avibactam powder for concentrate for solution for infusion 2000 mg/500 mg Plus Metronidazole 500mg/100ml solution for infusion
Meropenem powder for solution for infusion 1000mg
Overall Number of Participants Analyzed 100 119
Measure Type: Number
Unit of Measure: Number of patients
Favorable 93 113
Unfavorable 7 6
18.Secondary Outcome
Title The Proportion of Patients With a Favorable Per-patient Microbiological Response at the Late Follow up (LFU) Visit in the Extended Microbiologically Evaluable (ME) Analysis Set.
Hide Description Per-patient "favorable" response indicates that all of the patient's baseline pathogens are "eradicated" or "presumed eradicated".
Time Frame At the late follow up (LFU) (Day 42 to 49)
Hide Outcome Measure Data
Hide Analysis Population Description
Extended microbiologically evaluable (ME) analysis set defined as all patients included in the clinically evaluable (CE) set with at least 1 Gram-negative aerobic pathogen in the initial/prestudy culture regardless of susceptibility.
Arm/Group Title Ceftazidime-Avibactam Plus Metronidazole Meropenem
Hide Arm/Group Description:
Ceftazidime-Avibactam powder for concentrate for solution for infusion 2000 mg/500 mg Plus Metronidazole 500mg/100ml solution for infusion
Meropenem powder for solution for infusion 1000mg
Overall Number of Participants Analyzed 97 112
Measure Type: Number
Unit of Measure: Number of patients
Favorable 90 106
Unfavorable 7 6
19.Secondary Outcome
Title The Proportion of Patients With a Favorable Per-patient Microbiological Response at the End of Treatment (EOT) Visit in the Microbiological Modified Intent-to-treat (mMITT) Analysis Set.
Hide Description Per-patient "favorable" response indicates that all of the patient's baseline pathogens are "eradicated" or "presumed eradicated".
Time Frame At the end of treatment (EOT) (within 24 hours after last IV dose)
Hide Outcome Measure Data
Hide Analysis Population Description
The microbiological modified intent-to-treat (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 Ceftazidime-Avibactam Plus Metronidazole Meropenem
Hide Arm/Group Description:
Ceftazidime-Avibactam powder for concentrate for solution for infusion 2000 mg/500 mg Plus Metronidazole 500mg/100ml solution for infusion
Meropenem powder for solution for infusion 1000mg
Overall Number of Participants Analyzed 143 152
Measure Type: Number
Unit of Measure: Number of patients
Favorable 126 140
Unfavorable 6 7
Indeterminate 11 5
20.Secondary Outcome
Title The Proportion of Patients With a Favorable Per-patient Microbiological Response at the Test of Cure (TOC) Visit in the Microbiological Modified Intent-to-treat (mMITT) Analysis Set.
Hide Description Per-patient "favorable" response indicates that all of the patient's baseline pathogens are "eradicated" or "presumed eradicated".
Time Frame At the test of cure (TOC) (Day 28 to 35)
Hide Outcome Measure Data
Hide Analysis Population Description
The microbiological modified intent-to-treat (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 Ceftazidime-Avibactam Plus Metronidazole Meropenem
Hide Arm/Group Description:
Ceftazidime-Avibactam powder for concentrate for solution for infusion 2000 mg/500 mg Plus Metronidazole 500mg/100ml solution for infusion
Meropenem powder for solution for infusion 1000mg
Overall Number of Participants Analyzed 143 152
Measure Type: Number
Unit of Measure: Number of patients
Favorable 119 135
Unfavorable 10 9
Indeterminate 14 8
21.Secondary Outcome
Title The Proportion of Patients With a Favorable Per-patient Microbiological Response at the Late Follow up (LFU) Visit in the Microbiological Modified Intent-to-treat (mMITT) Analysis Set.
Hide Description Per-patient "favorable" response indicates that all of the patient's baseline pathogens are "eradicated" or "presumed eradicated".
Time Frame At the late follow up (LFU) (Day 42 to 49)
Hide Outcome Measure Data
Hide Analysis Population Description
The microbiological modified intent-to-treat (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 Ceftazidime-Avibactam Plus Metronidazole Meropenem
Hide Arm/Group Description:
Ceftazidime-Avibactam powder for concentrate for solution for infusion 2000 mg/500 mg Plus Metronidazole 500mg/100ml solution for infusion
Meropenem powder for solution for infusion 1000mg
Overall Number of Participants Analyzed 143 152
Measure Type: Number
Unit of Measure: Number of patients
Favorable 116 132
Unfavorable 10 9
Indeterminate 17 11
22.Secondary Outcome
Title The Proportion of Favorable Per-pathogen Microbiological Response at the End of Treatment (EOT) Visit in the Microbiological Modified Intent-to-treat (mMITT) Analysis Set.
Hide Description The proportion 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 At the end of treatment (EOT) (within 24 hours after last IV dose)
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 Ceftazidime-Avibactam Plus Metronidazole Meropenem
Hide Arm/Group Description:
Ceftazidime-Avibactam powder for concentrate for solution for infusion 2000 mg/500 mg Plus Metronidazole 500mg/100ml solution for infusion (summary only shows pathogens where N>/=10)
Meropenem powder for solution for infusion 1000mg
Overall Number of Participants Analyzed 143 152
Measure Type: Number
Unit of Measure: Participants with favorable responses
Escherichia coli (n=84, 89) 77 86
Klebsiella oxytoca (n=5, 5) 5 5
Klebsiella pneumoniae (n=28,35) 22 32
Pseudomonas aeruginosa (n=17, 20) 15 17
Streptococcus anginosus grou (n=8, 7) 7 6
Streptococcus mitis group (n=6, 5) 6 5
Enterococcus faecalis (n=6, 6) 5 5
Enterococcus faecium (n=4, 7) 4 5
23.Secondary Outcome
Title The Proportion of Favorable Per-pathogen Microbiological Response in the Microbiological Response at the Test of Cure (TOC) Visit in the Microbiological Modified Intent-to-treat (mMITT) Analysis Set.
Hide Description The proportion 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 At the test of cure (TOC) (Day 28 to 35)
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 Ceftazidime-Avibactam Plus Metronidazole Meropenem
Hide Arm/Group Description:
Ceftazidime-Avibactam powder for concentrate for solution for infusion 2000 mg/500 mg Plus Metronidazole 500mg/100ml solution for infusion (summary only shows pathogens where N>/=10)
Meropenem powder for solution for infusion 1000mg
Overall Number of Participants Analyzed 143 152
Measure Type: Number
Unit of Measure: Participants with favorable responses
Escherichia coli (n=84, 89) 70 84
Klebsiella oxytoca (n=5, 5) 5 5
Klebsiella pneumoniae (n=28,35) 23 31
Pseudomonas aeruginosa (n=17, 20) 14 17
Streptococcus anginosus group (n=8, 7) 7 5
Streptococcus mitis group (n=6, 5) 6 5
Enterococcus faecalis (n=6, 6) 6 4
Enterococcus faecium (n=4, 7) 4 5
24.Secondary Outcome
Title The Proportion of Favorable Per-pathogen Microbiological Response in the Microbiological Response at the Late Follow up (LFU) Visit in the Microbiological Modified Intent-to-treat (mMITT) Analysis Set.
Hide Description The proportion 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 At the late follow up (LFU) (Day 42 to 49)
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 Ceftazidime-Avibactam Plus Metronidazole Meropenem
Hide Arm/Group Description:
Ceftazidime-Avibactam powder for concentrate for solution for infusion 2000 mg/500 mg Plus Metronidazole 500mg/100ml solution for infusion (summary only shows pathogens where N>/=10)
Meropenem powder for solution for infusion 1000mg
Overall Number of Participants Analyzed 143 152
Measure Type: Number
Unit of Measure: Participants with favorable responses
Escherichia coli (n=84, 89) 70 82
Klebsiella pneumoniae (n=28, 35) 22 31
Pseudomonas aeruginosa (n=17, 20) 14 17
Klebsiella oxytoca (n=5, 5) 4 5
Enterococcus faecalis (n=6, 6) 4 4
Enterococcus faecium (n=4, 7) 3 5
Streptococcus anginosus group (n=8, 7) 7 5
Streptococcus mitis group (n=6, 5) 6 5
25.Secondary Outcome
Title The Proportion of Favorable Per-pathogen Microbiological Response at the End of Treatment (EOT) Visit in the Microbiologically Evaluable (ME) Analysis Set.
Hide Description The proportion 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 At the end of treatment (EOT) (within 24 hours after last IV dose)
Hide Outcome Measure Data
Hide Analysis Population Description
Microbiologically evaluable (ME) analysis set defined as all patients included in the clinically evaluable (CE) set with at least 1 Gram-negative aerobic pathogen in the initial/prestudy culture that was susceptible to both treatment groups.
Arm/Group Title Ceftazidime-Avibactam Plus Metronidazole Meropenem
Hide Arm/Group Description:
Ceftazidime-Avibactam powder for concentrate for solution for infusion 2000 mg/500 mg Plus Metronidazole 500mg/100ml solution for infusion (summary only shows pathogens where N>/=10)
Meropenem powder for solution for infusion 1000mg
Overall Number of Participants Analyzed 99 113
Measure Type: Number
Unit of Measure: Participants with favorable responses
Escherichia coli (n=69, 77) 68 75
Klebsiella oxytoca (n=5, 5) 5 5
Klebsiella pneumoniae (n=22, 29) 21 28
Pseudomonas aeruginosa (n=14, 16) 14 14
26.Secondary Outcome
Title The Proportion of Favorable Per-pathogen Microbiological Response at the Test of Cure (TOC) Visit in the Microbiologically Evaluable (ME) Analysis Set.
Hide Description The proportion 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 At the test of cure (TOC) (Day 28 to 35)
Hide Outcome Measure Data
Hide Analysis Population Description
Microbiologically evaluable (ME) analysis set defined as all patients included in the clinically evaluable (CE) set with at least 1 Gram-negative aerobic pathogen in the initial/prestudy culture that was susceptible to both treatment groups.
Arm/Group Title Ceftazidime-Avibactam Plus Metronidazole Meropenem
Hide Arm/Group Description:
Ceftazidime-Avibactam powder for concentrate for solution for infusion 2000 mg/500 mg Plus Metronidazole 500mg/100ml solution for infusion (summary only shows pathogens where N>/=10)
Meropenem powder for solution for infusion 1000mg
Overall Number of Participants Analyzed 99 113
Measure Type: Number
Unit of Measure: Participants with favorable responses
Escherichia coli (n=69, 77) 64 74
Klebsiella oxytoca (n=5, 5) 5 5
Klebsiella pneumoniae (n=22, 29) 21 28
Pseudomonas aeruginosa (n=14, 16) 13 14
27.Secondary Outcome
Title The Proportion of Favorable Per-pathogen Microbiological Response at the Late Follow up (LFU) Visit in the Microbiologically Evaluable (ME) Analysis Set.
Hide Description The proportion 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 At the late follow up (LFU) (Day 42 to 49)
Hide Outcome Measure Data
Hide Analysis Population Description
Microbiologically evaluable (ME) analysis set defined as all patients included in the clinically evaluable (CE) set with at least 1 Gram-negative aerobic pathogen in the initial/prestudy culture that was susceptible to both treatment groups.
Arm/Group Title Ceftazidime-Avibactam Plus Metronidazole Meropenem
Hide Arm/Group Description:
Ceftazidime-Avibactam powder for concentrate for solution for infusion 2000 mg/500 mg Plus Metronidazole 500mg/100ml solution for infusion (summary only shows pathogens where N>/=10)
Meropenem powder for solution for infusion 1000mg
Overall Number of Participants Analyzed 99 113
Measure Type: Number
Unit of Measure: Participants with favorable responses
Escherichia coli (n=69, 77) 63 72
Klebsiella oxytoca (n=5, 5) 4 5
Klebsiella pneumoniae (n=22, 29) 21 27
Pseudomonas aeruginosa (n=14, 16) 13 14
28.Secondary Outcome
Title The Proportion of Favorable Per-pathogen Microbiological Response at the End of Treatment (EOT) Visit in the Extended Microbiologically Evaluable (ME) Analysis Set.
Hide Description The proportion 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 At the end of treatment (EOT) (within 24 hours after last IV dose)
Hide Outcome Measure Data
Hide Analysis Population Description
Extended microbiologically evaluable(ME) analysis set defined as all patients included in the clinically evaluable (CE) set with at least 1 Gram-negative aerobic pathogen in the initial/prestudy culture regardless of susceptibility.
Arm/Group Title Ceftazidime-Avibactam Plus Metronidazole Meropenem
Hide Arm/Group Description:
Ceftazidime-Avibactam powder for concentrate for solution for infusion 2000 mg/500 mg Plus Metronidazole 500mg/100ml solution for infusion (summary only shows pathogens where N>/=10)
Meropenem powder for solution for infusion 1000mg
Overall Number of Participants Analyzed 100 119
Measure Type: Number
Unit of Measure: Participants with favorable responses
Escherichia coli (n=70, 80) 69 78
Klebsiella oxytoca (n=5, 5) 5 5
Klebsiella pneumoniae (n=22, 30) 21 29
Pseudomonas aeruginosa (n=14, 18) 14 16
29.Secondary Outcome
Title The Proportion of Favorable Per-pathogen Microbiological Response at the Test of Cure (TOC) Visit in the Extended Microbiologically Evaluable(ME) Analysis Set.
Hide Description The proportion 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 At the test of cure (TOC) (Day 28 to 35)
Hide Outcome Measure Data
Hide Analysis Population Description
Extended microbiologically evaluable(ME) analysis set defined as all patients included in the clinically evaluable (CE) set with at least 1 Gram-negative aerobic pathogen in the initial/prestudy culture regardless of susceptibility.
Arm/Group Title Ceftazidime-Avibactam Plus Metronidazole Meropenem
Hide Arm/Group Description:
Ceftazidime-Avibactam powder for concentrate for solution for infusion 2000 mg/500 mg Plus Metronidazole 500mg/100ml solution for infusion (summary only shows pathogens where N>/=10)
Meropenem powder for solution for infusion 1000mg
Overall Number of Participants Analyzed 100 119
Measure Type: Number
Unit of Measure: Participants with favorable responses
Escherichia coli (n=70, 80) 65 77
Klebsiella oxytoca (n=5, 5) 5 5
Klebsiella pneumoniae (n=22, 30) 21 29
Pseudomonas aeruginosa (n=14, 18) 13 16
30.Secondary Outcome
Title The Proportion of Favorable Per-pathogen Microbiological Response at the Late Follow up (LFU) Visit in the Extended Microbiologically Evaluable (ME) Analysis Set.
Hide Description The proportion 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 At the late follow up (LFU) (Day 42 to 49)
Hide Outcome Measure Data
Hide Analysis Population Description
Extended microbiologically evaluable(ME) analysis set defined as all patients included in the clinically evaluable (CE) set with at least 1 Gram-negative aerobic pathogen in the initial/prestudy culture regardless of susceptibility.
Arm/Group Title Ceftazidime-Avibactam Plus Metronidazole Meropenem
Hide Arm/Group Description:
Ceftazidime-Avibactam powder for concentrate for solution for infusion 2000 mg/500 mg Plus Metronidazole 500mg/100ml solution for infusion (summary only shows pathogens where N>/=10)
Meropenem powder for solution for infusion 1000mg
Overall Number of Participants Analyzed 100 119
Measure Type: Number
Unit of Measure: Participants with favorable responses
Escherichia coli (n=70, 80) 64 75
Klebsiella oxytoca (n=5, 5) 4 5
Klebsiella pneumoniae (n=22, 30) 21 28
Pseudomonas aeruginosa (n=14, 18) 13 16
31.Secondary Outcome
Title The Proportion of Patients With a Favorable Per Patient Microbiological Response at the Test of Cure (TOC) Visit for Patients Infected With Ceftazidime Resistant Pathogens in the Microbiological Modified Intent-to-treat (mMITT) Analysis Set.
Hide Description The 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 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 At the test of cure (TOC) (Day 28 to 35)
Hide Outcome Measure Data
Hide Analysis Population Description
The microbiological modified intent-to-treat (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 Ceftazidime-Avibactam Plus Metronidazole Meropenem
Hide Arm/Group Description:
Ceftazidime-Avibactam powder for concentrate for solution for infusion 2000 mg/500 mg Plus Metronidazole 500mg/100ml solution for infusion
Meropenem powder for solution for infusion 1000mg
Overall Number of Participants Analyzed 29 29
Measure Type: Number
Unit of Measure: Number of patients
Favorable 24 27
Unfavorable 1 1
Indeterminate 4 1
32.Secondary Outcome
Title The Proportion of Patients With a Favorable Per Patient Microbiological Response at the Test of Cure (TOC) Visit for Patients Infected With Ceftazidime Resistant Pathogens in the Microbiologically Evaluable (ME) Analysis Set.
Hide Description The 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 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 At the test of cure (TOC) (Day 28 to 35)
Hide Outcome Measure Data
Hide Analysis Population Description
Microbiologically evaluable (ME) analysis set defined as all patients included in the clinically evaluable (CE) set with at least 1 Gram-negative aerobic pathogen in the initial/prestudy culture that was susceptible to both treatment groups.
Arm/Group Title Ceftazidime-Avibactam Plus Metronidazole Meropenem
Hide Arm/Group Description:
Ceftazidime-Avibactam powder for concentrate for solution for infusion 2000 mg/500 mg Plus Metronidazole 500mg/100ml solution for infusion
Meropenem powder for solution for infusion 1000mg
Overall Number of Participants Analyzed 23 24
Measure Type: Number
Unit of Measure: Number of patients
Favorable 22 23
Unfavorable 1 1
33.Secondary Outcome
Title The Proportion of Patients With a Favorable Per Patient Microbiological Response at the Test of Cure (TOC) Visit for Patients Infected With Ceftazidime Resistant Pathogens in the Extended Microbiologically Evaluable (ME) Analysis Set.
Hide Description The 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 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 At the test of cure (TOC) (Day 28 to 35)
Hide Outcome Measure Data
Hide Analysis Population Description
Extended microbiologically evaluable(ME) analysis set defined as all patients included in the clinically evaluable (CE) set with at least 1 Gram-negative aerobic pathogen in the initial/prestudy culture regardless of susceptibility.
Arm/Group Title Ceftazidime-Avibactam Plus Metronidazole Meropenem
Hide Arm/Group Description:
Ceftazidime-Avibactam powder for concentrate for solution for infusion 2000 mg/500 mg Plus Metronidazole 500mg/100ml solution for infusion
Meropenem powder for solution for infusion 1000mg
Overall Number of Participants Analyzed 23 26
Measure Type: Number
Unit of Measure: Number of patients
Favorable 22 25
Unfavorable 1 1
34.Secondary Outcome
Title The Time to First Defervescence in the Clinically Evaluable (CE) 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 to first defervescence while on IV study therapy in the CE analysis set at TOC for patients who had fever at study entry is defined as time (in days) from the first dose of IV study therapy to first absence of fever.
Time Frame while on study therapy (from Day 1 to Day 14)
Hide Outcome Measure Data
Hide Analysis Population Description
Clinically evaluable (CE) with fever, defined as >38ºC at study entry. No participants were censored at the time of last observation.
Arm/Group Title Ceftazidime-Avibactam Plus Metronidazole Meropenem
Hide Arm/Group Description:
Ceftazidime-Avibactam powder for concentrate for solution for infusion 2000 mg/500 mg Plus Metronidazole 500mg/100ml solution for infusion
Meropenem powder for solution for infusion 1000mg
Overall Number of Participants Analyzed 17 26
Median (Full Range)
Unit of Measure: Days
1
(1 to 5)
1.5
(1 to 4)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ceftazidime-Avibactam Plus Metronidazole, Meropenem
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.773
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in median time (days)
Estimated Value 0.5
Estimation Comments [Not Specified]
35.Secondary Outcome
Title The Time to First Defervescence in the Microbiological Modified Intent-to-treat (mMITT) 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 to first defervescence while on IV study therapy in the CE analysis set at TOC for patients who had fever at study entry is defined as time (in days) from the first dose of IV study therapy to first absence of fever.
Time Frame while on study therapy (from Day 1 to Day 14)
Hide Outcome Measure Data
Hide Analysis Population Description
microbiological modified intent-to-treat (mMITT) with fever, defined as >38ºC at study entry. No participants were censored at the time of last observation.
Arm/Group Title Ceftazidime-Avibactam Plus Metronidazole Meropenem
Hide Arm/Group Description:
Ceftazidime-Avibactam powder for concentrate for solution for infusion 2000 mg/500 mg Plus Metronidazole 500mg/100ml solution for infusion
Meropenem powder for solution for infusion 1000mg
Overall Number of Participants Analyzed 16 26
Median (Full Range)
Unit of Measure: Days
1
(1 to 5)
2
(1 to 4)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ceftazidime-Avibactam Plus Metronidazole, Meropenem
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.598
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in median time (days)
Estimated Value 1
Estimation Comments [Not Specified]
36.Secondary Outcome
Title Safety and Tolerability by Incidence and Severity of Adverse Events and Serious Adverse Events and Mortality.
Hide Description Adverse event data were collected from the screening/consent visit until the late follow-up visit (i.e. Day -1/0 to Day 42).
Time Frame study duration (from screening to Day 49 LFU visit)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set: all patients who received at least 1 dose of IP
Arm/Group Title Ceftazidime-Avibactam Plus Metronidazole Meropenem
Hide Arm/Group Description:
Ceftazidime-Avibactam powder for concentrate for solution for infusion 2000 mg/500 mg Plus Metronidazole 500mg/100ml solution for infusion
Meropenem powder for solution for infusion 1000mg
Overall Number of Participants Analyzed 215 217
Measure Type: Number
Unit of Measure: Number of patients
Any AE 82 83
Any SAE 9 11
Any AE leading to discontinuation of IP 7 3
Any AE of severe intensity 5 5
Total number of deaths 2 1
Deaths due to disease progression 2 0
Any AE with outcome=death 0 1
37.Secondary Outcome
Title Safety and Tolerability by Incidence: Extent of Exposure.
Hide Description Duration of exposure is calculated as the difference between the last study therapy date and the first study therapy date converted to days plus 1 day. Actual calculated duration could be shorter or longer than a full day.
Time Frame study duration (from screening to Day 49 LFU visit)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set: all patients who received at least 1 dose of IP
Arm/Group Title Ceftazidime-Avibactam Plus Metronidazole Meropenem
Hide Arm/Group Description:
Ceftazidime-Avibactam powder for concentrate for solution for infusion 2000 mg/500 mg Plus Metronidazole 500mg/100ml solution for infusion
Meropenem powder for solution for infusion 1000mg
Overall Number of Participants Analyzed 215 217
Measure Type: Number
Unit of Measure: Number of patients
1 - 2 days 10 5
3 - 4 days 6 5
5 -10 days 175 181
11 - 14 days 24 26
>14 days 0 0
38.Secondary Outcome
Title Safety and Tolerability: Clinical Laboratory Evaluation Hematology.
Hide Description Potentially clinically significant (PCS) post Baseline hematology values up to LFU (Safety analysis set)
Time Frame study duration (from screening to Day 49 LFU visit)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set: all patients who received at least 1 dose of IP
Arm/Group Title Ceftazidime-Avibactam Plus Metronidazole Meropenem
Hide Arm/Group Description:
Ceftazidime-Avibactam powder for concentrate for solution for infusion 2000 mg/500 mg Plus Metronidazole 500mg/100ml solution for infusion
Meropenem powder for solution for infusion 1000mg
Overall Number of Participants Analyzed 215 217
Measure Type: Number
Unit of Measure: Number of patients
Platelet count: PCS (Low) 1 1
Platelet count: PCS (High) 5 4
Red blood cell count: PCS (Low) 7 13
Red blood cell count: PCS (High) 0 0
White blood cell: PCS (Low) 1 1
White blood cell: PCS (High) 4 5
Hemoglobin: PCS (Low) 7 14
Hemoglobin: PCS (High) 0 0
Lymphocytes: PCS (Low) 1 1
Lymphocytes: PCS (High) 0 1
Neutrophils: PCS (Low) 4 2
Neutrophils: PCS (High) 9 8
Eosinophils: PCS (High) 0 0
Monocytes: PCS (High) 0 0
Basophils: PCS (High) 0 0
Direct Coombs test:- at Baseline, + post-Baseline 15 2
Hematocrit (ratio): PCS (Low) 5 8
Hematocrit (ratio): PCS (High) 0 0
39.Secondary Outcome
Title Safety and Tolerability: Clinical Laboratory Evaluation Clinical Chemistry.
Hide Description Potentially clinically significant (PCS) post Baseline clinical chemistry values up to LFU (Safety analysis set)
Time Frame study duration (from screening to Day 49 LFU visit)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set: all patients who received at least 1 dose of IP
Arm/Group Title Ceftazidime-Avibactam Plus Metronidazole Meropenem
Hide Arm/Group Description:
Ceftazidime-Avibactam powder for concentrate for solution for infusion 2000 mg/500 mg Plus Metronidazole 500mg/100ml solution for infusion
Meropenem powder for solution for infusion 1000mg
Overall Number of Participants Analyzed 215 217
Measure Type: Number
Unit of Measure: Number of patients
Alanine aminotransferase (μkat/L): PCS (High) 3 8
Alkaline phosphatase (μkat/L): PCS (Low) 0 0
Alkaline phosphatase (μkat/L): PCS (High) 2 3
Aspartate aminotransferase (μkat/L): PCS (High) 4 4
Bicarbonate (mmol/L) PCS (Low) 1 0
Bicarbonate (mmol/L): PCS (High) 0 0
Creatinine (μmol/L): PCS (High) 0 1
Glucose (non-fasting) (mmol/L): PCS (Low) 0 0
Glucose (non-fasting) (mmol/L): PCS (High) 1 1
Gamma-glutamyl transferase (μkat/L):PCS (High) 2 4
Inorganic phosphorus (mmol/L): PCS (Low) 3 7
Inorganic phosphorus (mmol/L): PCS (High) 0 0
Potassium (mmol/L): PCS (Low) 9 5
Potassium (mmol/L): PCS (High) 3 1
Total bilirubin (μmol/L): PCS (High) 0 1
Direct bilirubin (μmol/L): PCS (High) 1 1
40.Secondary Outcome
Title Safety and Tolerability:ECG , QTcB and QTcF Intervals
Hide Description Shifts in ECG interpretation and changes in QT, QTcB, and QTcF intervals , from baseline to post baseline.
Time Frame EOT visit/any observation on treatment
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set: all patients who received at least 1 dose of IP
Arm/Group Title Ceftazidime-Avibactam Plus Metronidazole Meropenem
Hide Arm/Group Description:
Ceftazidime-Avibactam powder for concentrate for solution for infusion 2000 mg/500 mg Plus Metronidazole 500mg/100ml solution for infusion
Meropenem powder for solution for infusion 1000mg
Overall Number of Participants Analyzed 215 217
Measure Type: Number
Unit of Measure: Number of patients
Normal to Abnormal: EOT 17 14
Normal to Abnormal: Anytime up to EOT 34 30
Reaching a value in QT: ≥450 (ms) 9 10
Reaching a value in QT: ≥480 (ms) 2 1
Reaching a value in QT: ≥500 (ms) 0 0
QT: ≥500 and increase from Baseline ≥60(ms) 0 0
Increase in QT: ≥30 (ms) 115 114
Increase in QT: ≥60 (ms) 50 44
Decrease in QT: ≥30 (ms) 24 24
Decrease in QT: ≥60 (ms) 12 4
Reaching a value in QTcB: ≥450(ms) 57 63
Reaching a value in QTcB: ≥480(ms) 13 8
Reaching a value in QTcB: ≥500 (ms) 4 2
QTcB: ≥500 and increase from Baseline ≥60(ms) 2 1
Increase in QTcB: ≥30 (ms) 21 27
Increase in QTcB: ≥60 (ms) 2 1
Decrease in QTcB: ≥30 (ms) 42 26
Decrease in QTcB: ≥60 (ms) 6 4
Reaching a value in QTcF: ≥450 (ms) 19 18
Reaching a value in QTcF: ≥480 (ms) 4 0
Reaching a value in QTcF: ≥500 (ms) 1 0
QTcF: ≥500 and increase from Baseline ≥60 (ms) 0 0
Increase in QTcF: ≥30 (ms) 42 41
Increase in QTcF: ≥60 (ms) 4 3
Decrease QTcF: ≥30 (ms) 21 19
Decrease QTcF: ≥60 (ms) 7 1
41.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 At Day 3: 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 Ceftazidime(1) Avibactam(1) Ceftazidime(2) Avibactam(2) Ceftazidime(3) Avibactam(3)
Hide Arm/Group Description:
15 minutes before or after
15 minutes before or after
30-90 minutes after
30-90 minutes after
300-360 minutes after
300-360 minutes after
Overall Number of Participants Analyzed 195 195 193 193 192 192
Geometric Mean (Full Range)
Unit of Measure: ng/mL
60300.4
(1390 to 1880000)
10126.9
(197 to 435000)
46473.9
(2080 to 210000)
7289.3
(229 to 36300)
9555.0
(1740 to 222000)
1207.2
(227 to 36300)
Time Frame Adverse event data were collected from the screening/consent visit until the late follow-up visit (i.e. Day -1/0 to Day 42). FOR SAE's - only those reported by 2 or more patients in either group are shown in this summary.
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 Plus Metronidazole Meropenem
Hide Arm/Group Description [Not Specified] Meropenem powder for solution for infusion 1000mg
All-Cause Mortality
CAZ-AVI Plus Metronidazole Meropenem
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
CAZ-AVI Plus Metronidazole Meropenem
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   9/215 (4.19%)      11/217 (5.07%)    
Blood and lymphatic system disorders     
Anaemia  1  1/215 (0.47%)  1 0/217 (0.00%)  0
Cardiac disorders     
Arteriosclerosis coronary artery  1  1/215 (0.47%)  1 0/217 (0.00%)  0
Gastrointestinal disorders     
Abdominal pain lower  1  1/215 (0.47%)  1 0/217 (0.00%)  0
Gastric ulcer  1  0/215 (0.00%)  0 1/217 (0.46%)  1
Gastritis  1  1/215 (0.47%)  1 0/217 (0.00%)  0
Ileus  1  0/215 (0.00%)  0 1/217 (0.46%)  1
General disorders     
Impaired healing  1  0/215 (0.00%)  0 1/217 (0.46%)  1
Pyrexia  1  0/215 (0.00%)  0 1/217 (0.46%)  1
Hepatobiliary disorders     
Cholangitis acute  1  1/215 (0.47%)  1 0/217 (0.00%)  0
Hepatic function abnormal  1  1/215 (0.47%)  1 0/217 (0.00%)  0
Infections and infestations     
Abdominal infection  1  1/215 (0.47%)  1 0/217 (0.00%)  0
Pneumonia  1  0/215 (0.00%)  0 1/217 (0.46%)  1
Postoperative wound infection  1  1/215 (0.47%)  1 1/217 (0.46%)  1
Injury, poisoning and procedural complications     
Incision site complication  1  0/215 (0.00%)  0 1/217 (0.46%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Metastasis  1  1/215 (0.47%)  1 0/217 (0.00%)  0
Non-Hodgkin's lymphoma  1  0/215 (0.00%)  0 1/217 (0.46%)  1
Psychiatric disorders     
Confusional state  1  0/215 (0.00%)  0 1/217 (0.46%)  1
Renal and urinary disorders     
Acute kidney injury  1  1/215 (0.47%)  1 1/217 (0.46%)  1
Respiratory, thoracic and mediastinal disorders     
Acute respiratory distress syndrome  1  1/215 (0.47%)  1 0/217 (0.00%)  0
Laryngeal disorder  1  1/215 (0.47%)  1 0/217 (0.00%)  0
Pneumonia aspiration  1  0/215 (0.00%)  0 1/217 (0.46%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 18.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 2%
CAZ-AVI Plus Metronidazole Meropenem
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   44/215 (20.47%)      47/217 (21.66%)    
Gastrointestinal disorders     
Constipation  1  5/215 (2.33%)  5 3/217 (1.38%)  4
Diarrhoea  1  13/215 (6.05%)  14 16/217 (7.37%)  20
Nausea  1  18/215 (8.37%)  25 4/217 (1.84%)  4
Vomiting  1  5/215 (2.33%)  8 4/217 (1.84%)  5
General disorders     
Pyrexia  1  9/215 (4.19%)  12 12/217 (5.53%)  21
Hepatobiliary disorders     
Hepatic function abnormal  1  0/215 (0.00%)  0 6/217 (2.76%)  6
Nervous system disorders     
Headache  1  3/215 (1.40%)  3 5/217 (2.30%)  5
Respiratory, thoracic and mediastinal disorders     
Cough  1  3/215 (1.40%)  3 8/217 (3.69%)  8
Productive cough  1  5/215 (2.33%)  5 6/217 (2.76%)  6
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 18.0
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 investigator agrees not to use such Confidential study information and not to disclose them to any other third parties, except that the undersigned shall not be prevented from using or disclosing information: (a) which by written records was previously known; (b) which is now public knowledge, (c) which is lawfully obtained by the undersigned from sources who have a lawful right to disclose such information.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: David Wilson, Statistical Team Leader - Infection
Organization: AstraZeneca
Phone: +44 1625 517830
EMail: David.Wilson2@astrazeneca.com
Layout table for additonal information
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT01726023     History of Changes
Other Study ID Numbers: D4280C00018
2011-003893-97
First Submitted: November 5, 2012
First Posted: November 14, 2012
Results First Submitted: February 1, 2016
Results First Posted: April 14, 2016
Last Update Posted: September 6, 2017