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

Sponsor

Pfizer (Industry)

Overall Status

Completed

CT.gov ID

NCT01726023

Collaborator

(none)

486

Enrollment

Locations

Arms

25.9

Duration (Months)

16.2

Patients Per Site

0.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the effects of Ceftazidime Avibactam plus Metronidazole compared to Meropenem for treating hospitalized patients with complicated intra-abdominal infections.

Condition or Disease	Intervention/Treatment	Phase
Complicated Intra-abdominal Infection	Drug: Ceftazidime-avibactam Drug: metronidazole Drug: Meropenem	Phase 3

Detailed Description

A Phase III, Randomized, Multicenter, Double Blind, Double-Dummy, Parallel-Group, Comparative Study to Determine the Efficacy, Safety, and Tolerability of Ceftazidime Avibactam Plus Metronidazole Versus Meropenem in the Treatment of Complicated Intra-Abdominal Infections In Hospitalized Adults

Study Design

Study Type:

Interventional

Actual Enrollment :

486 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Study Start Date :

Jan 1, 2013

Actual Primary Completion Date :

Mar 1, 2015

Actual Study Completion Date :

Mar 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Ceftazidime-Avibactam plus metronidazole	Drug: Ceftazidime-avibactam Ceftazidime-Avibactam powder for concentrate for solution for infusion 2000 mg/500 mg Drug: metronidazole Metronidazole 500mg/100ml solution for infusion
Active Comparator: Meropenem	Drug: Meropenem Meropenem powder for solution for infusion 1000mg

Arm

Intervention/Treatment

Experimental: Ceftazidime-Avibactam plus metronidazole

Drug: Ceftazidime-avibactam

Ceftazidime-Avibactam powder for concentrate for solution for infusion 2000 mg/500 mg

Drug: metronidazole

Metronidazole 500mg/100ml solution for infusion

Active Comparator: Meropenem

Drug: Meropenem

Meropenem powder for solution for infusion 1000mg

Outcome Measures

Primary Outcome Measures

The Proportion of Patients With Clinical Cure at the Test of Cure (TOC) Visit in the Clinically Evaluable (CE) Analysis Set. [At the test of cure visit (Day 28 to35)]
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.

Secondary Outcome Measures

The Proportion of Patients With Clinical Cure at the End of Treatment (EOT) Visit in the Microbiologically Evaluable (ME) Analysis Set. [At the end of treatment (EOT) (within 24 hours after last IV dose)]
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.
The Proportion of Patients With Clinical Cure at the Test of Cure (TOC) Visit in the Microbiologically Evaluable (ME) Analysis Set. [At the test of cure (TOC) (Day 28 to 35)]
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.
The Proportion of Patients With Clinical Cure at the Late Follow up (LFU) Visit in the Microbiologically Evaluable (ME) Analysis Set. [At the late follow up (LFU) (Day 42 to 49)]
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.
The Proportion of Patients With Clinical Cure at the End of Treatment (EOT) Visit in the Extended Microbiologically Evaluable (ME) Analysis Set. [At the end of treatment (EOT) (within 24 hours after last IV dose)]
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.
The Proportion of Patients With Clinical Cure at the Test of Cure (TOC) Visit in the Extended Microbiologically Evaluable (ME) Analysis Set. [At the test of cure (TOC) (Day 28 to 35)]
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.
The Proportion of Patients With Clinical Cure at the Late Follow up (LFU) Visit in the Extended Microbiologically Evaluable (ME) Analysis Set. [At the late follow up (LFU) (Day 42 to 49)]
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.
The Proportion of Patients With Clinical Cure at the End of Treatment (EOT) Visit in the Microbiological Modified Intent-to-treat (mMITT) Analysis Set. [At the end of treatment (EOT) (within 24 hours after last IV dose)]
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.
The Proportion of Patients With Clinical Cure at the Test of Cure (TOC) Visit in the Microbiological Modified Intent-to-treat (mMITT) Analysis Set. [At the test of cure (TOC) (Day 28 to 35)]
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.
The Proportion of Patients With Clinical Cure at the Late Follow up (LFU) Visit in the Microbiological Modified Intent-to-treat (mMITT) Analysis Set. [At the late follow up (LFU) (Day 42 to 49)]
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.
The Proportion of Patients With Clinical Cure at the End of Treatment (EOT) Visit in the Clinically Evaluable (CE) Analysis Set. [At the end of treatment (EOT) (within 24 hours after last IV dose)]
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.
The Proportion of Patients With Clinical Cure at the Late Follow up (LFU) Visit in the Clinically Evaluable (CE) Analysis Set. [At late follow up (LFU) visits (Day 42 to 49)]
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.
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. [At the end of treatment (EOT) (within 24 hours after last IV dose)]
Per-patient "favorable" response indicates that all of the patient's baseline pathogens are "eradicated" or "presumed eradicated".
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. [At the test of cure (TOC) (Day 28 to 35)]
Per-patient "favorable" response indicates that all of the patient's baseline pathogens are "eradicated" or "presumed eradicated".
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. [At the late follow up (LFU) (Day 42 to 49)]
Per-patient "favorable" response indicates that all of the patient's baseline pathogens are "eradicated" or "presumed eradicated".
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. [At the end of treatment (EOT) (within 24 hours after last IV dose)]
Per-patient "favorable" response indicates that all of the patient's baseline pathogens are "eradicated" or "presumed eradicated".
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. [At the test of cure (TOC) (Day 28 to 35)]
Per-patient "favorable" response indicates that all of the patient's baseline pathogens are "eradicated" or "presumed eradicated".
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. [At the late follow up (LFU) (Day 42 to 49)]
Per-patient "favorable" response indicates that all of the patient's baseline pathogens are "eradicated" or "presumed eradicated".
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. [At the end of treatment (EOT) (within 24 hours after last IV dose)]
Per-patient "favorable" response indicates that all of the patient's baseline pathogens are "eradicated" or "presumed eradicated".
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. [At the test of cure (TOC) (Day 28 to 35)]
Per-patient "favorable" response indicates that all of the patient's baseline pathogens are "eradicated" or "presumed eradicated".
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. [At the late follow up (LFU) (Day 42 to 49)]
Per-patient "favorable" response indicates that all of the patient's baseline pathogens are "eradicated" or "presumed eradicated".
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. [At the end of treatment (EOT) (within 24 hours after last IV dose)]
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.
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. [At the test of cure (TOC) (Day 28 to 35)]
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.
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. [At the late follow up (LFU) (Day 42 to 49)]
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.
The Proportion of Favorable Per-pathogen Microbiological Response at the End of Treatment (EOT) Visit in the Microbiologically Evaluable (ME) Analysis Set. [At the end of treatment (EOT) (within 24 hours after last IV dose)]
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.
The Proportion of Favorable Per-pathogen Microbiological Response at the Test of Cure (TOC) Visit in the Microbiologically Evaluable (ME) Analysis Set. [At the test of cure (TOC) (Day 28 to 35)]
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.
The Proportion of Favorable Per-pathogen Microbiological Response at the Late Follow up (LFU) Visit in the Microbiologically Evaluable (ME) Analysis Set. [At the late follow up (LFU) (Day 42 to 49)]
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.
The Proportion of Favorable Per-pathogen Microbiological Response at the End of Treatment (EOT) Visit in the Extended Microbiologically Evaluable (ME) Analysis Set. [At the end of treatment (EOT) (within 24 hours after last IV dose)]
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.
The Proportion of Favorable Per-pathogen Microbiological Response at the Test of Cure (TOC) Visit in the Extended Microbiologically Evaluable(ME) Analysis Set. [At the test of cure (TOC) (Day 28 to 35)]
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.
The Proportion of Favorable Per-pathogen Microbiological Response at the Late Follow up (LFU) Visit in the Extended Microbiologically Evaluable (ME) Analysis Set. [At the late follow up (LFU) (Day 42 to 49)]
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.
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. [At the test of cure (TOC) (Day 28 to 35)]
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).
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. [At the test of cure (TOC) (Day 28 to 35)]
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).
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. [At the test of cure (TOC) (Day 28 to 35)]
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).
The Time to First Defervescence in the Clinically Evaluable (CE) Analysis Set for Patients Who Have Fever at Study Entry. [while on study therapy (from Day 1 to Day 14)]
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.
The Time to First Defervescence in the Microbiological Modified Intent-to-treat (mMITT) Analysis Set for Patients Who Have Fever at Study Entry. [while on study therapy (from Day 1 to Day 14)]
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.
Safety and Tolerability by Incidence and Severity of Adverse Events and Serious Adverse Events and Mortality. [study duration (from screening to Day 49 LFU visit)]
Adverse event data were collected from the screening/consent visit until the late follow-up visit (i.e. Day -1/0 to Day 42).
Safety and Tolerability by Incidence: Extent of Exposure. [study duration (from screening to Day 49 LFU visit)]
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.
Safety and Tolerability: Clinical Laboratory Evaluation Hematology. [study duration (from screening to Day 49 LFU visit)]
Potentially clinically significant (PCS) post Baseline hematology values up to LFU (Safety analysis set)
Safety and Tolerability: Clinical Laboratory Evaluation Clinical Chemistry. [study duration (from screening to Day 49 LFU visit)]
Potentially clinically significant (PCS) post Baseline clinical chemistry values up to LFU (Safety analysis set)
Safety and Tolerability:ECG , QTcB and QTcF Intervals [EOT visit/any observation on treatment]
Shifts in ECG interpretation and changes in QT, QTcB, and QTcF intervals , from baseline to post baseline.
Plasma Concentrations for Ceftazidime and Avibactam [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.]
Blood samples were taken from all patients on Day 3 for the pharmacokinetic evaluation of ceftazidime and avibactam plasma concentrations

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 90 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patient must be 18 to 90 years of age, inclusive,
Female patients can participate if they are surgically sterilized or postmenopausal for at least 1 year or her sexual partner has had a vasectomy
Female of childbearing potential has had normal menstrual periods for 3 months and negative serum pregnancy test and agree to practice highly effective methods of birth control during treatment and for at least 7 days after last dose
Intraoperative/postoperative enrollment with visual confirmation (presence of pus within the abdominal cavity) of an intra-abdominal infection associated with peritonitis
Confirmation of infection by surgical intervention within 24 hours of entry: evidence of systemic inflammatory indicators; physical findings consistent with intra-abdominal infection; supportive radiologic imaging findings of intra-abdominal infections

Exclusion Criteria:

Patient is diagnosed with traumatic bowel perforation undergoing surgery within 12 hours; perforation of gastroduodenal ulcers undergoing surgery within 24 hours. Other intra-abdominal processes in which primary etiology is not likely to be infectious
Patient has abdominal wall abscess or bowel obstruction without perforation or ischemic bowel without perforation
Patients whose surgery will include staged abdominal repair, or "open abdomen" technique, or marsupialization
Patient has suspected intra-abdominal infections due to fungus, parasites, virus or tuberculosis
Patient is considered unlikely to survive the 6- to 8-week study period or has a rapidly progressive or terminal illness, including septic shock that is associated with a high risk of mortality

Contacts and Locations

Locations

	Site	City	Country
1	Research Site	Baotou	China
2	Research Site	Beijing	China
3	Research Site	Changsha	China
4	Research Site	Chengdu	China
5	Research Site	Chongqing	China
6	Research Site	Fuzhou	China
7	Research Site	Guangzhou	China
8	Research Site	Guilin	China
9	Research Site	Haikou	China
10	Research Site	Hebei	China
11	Research Site	Jiangyin	China
12	Research Site	Liaocheng	China
13	Research Site	Nan Chang	China
14	Research Site	Shanghai	China
15	Research Site	Tianjin	China
16	Research Site	Urumqi	China
17	Research Site	Wenzhou	China
18	Research Site	Wuxi	China
19	Research Site	Xi'an	China
20	Research Site	Ansan-si	Korea, Republic of
21	Research Site	Anyang-si	Korea, Republic of
22	Research Site	Busan	Korea, Republic of
23	Research Site	Cheongju-si	Korea, Republic of
24	Research Site	Daejeon	Korea, Republic of
25	Research Site	Gwangju	Korea, Republic of
26	Research Site	Jinju-si	Korea, Republic of
27	Research Site	Seoul	Korea, Republic of
28	Research Site	Wonju-si	Korea, Republic of
29	Research Site	Hanoi	Vietnam
30	Research Site	Hochiminh	Vietnam

Sponsors and Collaborators

Pfizer

Investigators

Study Director: Paul A Newell, MBBS, MRCP, AstraZeneca

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Pfizer

ClinicalTrials.gov Identifier:

NCT01726023

Other Study ID Numbers:

D4280C00018
2011-003893-97

First Posted:

Nov 14, 2012

Last Update Posted:

Sep 6, 2017

Last Verified:

Sep 1, 2017

Keywords provided by Pfizer

Ceftazidime-avibactam,

Metronidazole,

Meropenem,

Anti-Bacterial Agents,

Anti-Infective Agents,

Therapeutic Uses,

Pharmacologic Actions,

Physiological Effects of Drugs

Additional relevant MeSH terms:

Infections

Communicable Diseases

Intraabdominal Infections

Avibactam, ceftazidime drug combination

Study Results

Participant Flow

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 Detail	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
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

Baseline Characteristics

Arm/Group Title	Ceftazidime-Avibactam Plus Metronidazole	Meropenem	Total
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 Participants	214	217	431
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	48.5 (16.83)	48.5 (17.43)	48.5 (17.11)
Age, Customized (Number) [Number]
18-45 Years	89 41.6%	96 44.2%	185 42.9%
46-64 Years	85 39.7%	72 33.2%	157 36.4%
65-74 Years	28 13.1%	30 13.8%	58 13.5%
75-90 Years	12 5.6%	19 8.8%	31 7.2%
Sex: Female, Male (Count of Participants)
Female	73 34.1%	64 29.5%	137 31.8%
Male	141 65.9%	153 70.5%	294 68.2%
Race/Ethnicity, Customized (Number) [Number]
Asian	214 100%	217 100%	431 100%

Outcome Measures

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.
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)

Outcome Measure Data

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
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
Measure Participants	177	184
Clinical cure	166	173
Clinical failure	11	11

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
	Parameter Dispersion	Type: Value:
	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.
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)

Outcome Measure Data

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
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
Measure Participants	106	118
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.
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)

Outcome Measure Data

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
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
Measure Participants	99	113
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.
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)

Outcome Measure Data

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
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
Measure Participants	96	106
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.
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)

Outcome Measure Data

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
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
Measure Participants	107	125
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.
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)

Outcome Measure Data

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
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
Measure Participants	100	119
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.
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)

Outcome Measure Data

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
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
Measure Participants	97	112
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.
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)

Outcome Measure Data

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
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
Measure Participants	143	152
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.
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)

Outcome Measure Data

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
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
Measure Participants	143	152
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.
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)

Outcome Measure Data

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
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
Measure Participants	143	152
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.
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)

Outcome Measure Data

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
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
Measure Participants	190	196
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.
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)

Outcome Measure Data

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
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
Measure Participants	168	179
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.
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)

Outcome Measure Data

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
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
Measure Participants	106	118
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.
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)

Outcome Measure Data

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
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
Measure Participants	99	113
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.
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)

Outcome Measure Data

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
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
Measure Participants	96	106
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.
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)

Outcome Measure Data

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
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
Measure Participants	107	125
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.
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)

Outcome Measure Data

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
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
Measure Participants	100	119
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.
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)

Outcome Measure Data

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
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
Measure Participants	97	112
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.
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)

Outcome Measure Data

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
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
Measure Participants	143	152
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.
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)

Outcome Measure Data

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
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
Measure Participants	143	152
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.
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)

Outcome Measure Data

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
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
Measure Participants	143	152
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.
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)

Outcome Measure Data

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
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
Measure Participants	143	152
Escherichia coli (n=84, 89)	77 36%	86 39.6%
Klebsiella oxytoca (n=5, 5)	5 2.3%	5 2.3%
Klebsiella pneumoniae (n=28,35)	22 10.3%	32 14.7%
Pseudomonas aeruginosa (n=17, 20)	15 7%	17 7.8%
Streptococcus anginosus grou (n=8, 7)	7 3.3%	6 2.8%
Streptococcus mitis group (n=6, 5)	6 2.8%	5 2.3%
Enterococcus faecalis (n=6, 6)	5 2.3%	5 2.3%
Enterococcus faecium (n=4, 7)	4 1.9%	5 2.3%

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.
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)

Outcome Measure Data

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
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
Measure Participants	143	152
Escherichia coli (n=84, 89)	70 32.7%	84 38.7%
Klebsiella oxytoca (n=5, 5)	5 2.3%	5 2.3%
Klebsiella pneumoniae (n=28,35)	23 10.7%	31 14.3%
Pseudomonas aeruginosa (n=17, 20)	14 6.5%	17 7.8%
Streptococcus anginosus group (n=8, 7)	7 3.3%	5 2.3%
Streptococcus mitis group (n=6, 5)	6 2.8%	5 2.3%
Enterococcus faecalis (n=6, 6)	6 2.8%	4 1.8%
Enterococcus faecium (n=4, 7)	4 1.9%	5 2.3%

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.
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)

Outcome Measure Data

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
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
Measure Participants	143	152
Escherichia coli (n=84, 89)	70 32.7%	82 37.8%
Klebsiella pneumoniae (n=28, 35)	22 10.3%	31 14.3%
Pseudomonas aeruginosa (n=17, 20)	14 6.5%	17 7.8%
Klebsiella oxytoca (n=5, 5)	4 1.9%	5 2.3%
Enterococcus faecalis (n=6, 6)	4 1.9%	4 1.8%
Enterococcus faecium (n=4, 7)	3 1.4%	5 2.3%
Streptococcus anginosus group (n=8, 7)	7 3.3%	5 2.3%
Streptococcus mitis group (n=6, 5)	6 2.8%	5 2.3%

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.
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)

Outcome Measure Data

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
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
Measure Participants	99	113
Escherichia coli (n=69, 77)	68 31.8%	75 34.6%
Klebsiella oxytoca (n=5, 5)	5 2.3%	5 2.3%
Klebsiella pneumoniae (n=22, 29)	21 9.8%	28 12.9%
Pseudomonas aeruginosa (n=14, 16)	14 6.5%	14 6.5%

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.
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)

Outcome Measure Data

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
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
Measure Participants	99	113
Escherichia coli (n=69, 77)	64 29.9%	74 34.1%
Klebsiella oxytoca (n=5, 5)	5 2.3%	5 2.3%
Klebsiella pneumoniae (n=22, 29)	21 9.8%	28 12.9%
Pseudomonas aeruginosa (n=14, 16)	13 6.1%	14 6.5%

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.
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)

Outcome Measure Data

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
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
Measure Participants	99	113
Escherichia coli (n=69, 77)	63 29.4%	72 33.2%
Klebsiella oxytoca (n=5, 5)	4 1.9%	5 2.3%
Klebsiella pneumoniae (n=22, 29)	21 9.8%	27 12.4%
Pseudomonas aeruginosa (n=14, 16)	13 6.1%	14 6.5%

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.
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)

Outcome Measure Data

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
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
Measure Participants	100	119
Escherichia coli (n=70, 80)	69 32.2%	78 35.9%
Klebsiella oxytoca (n=5, 5)	5 2.3%	5 2.3%
Klebsiella pneumoniae (n=22, 30)	21 9.8%	29 13.4%
Pseudomonas aeruginosa (n=14, 18)	14 6.5%	16 7.4%

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.
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)

Outcome Measure Data

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
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
Measure Participants	100	119
Escherichia coli (n=70, 80)	65 30.4%	77 35.5%
Klebsiella oxytoca (n=5, 5)	5 2.3%	5 2.3%
Klebsiella pneumoniae (n=22, 30)	21 9.8%	29 13.4%
Pseudomonas aeruginosa (n=14, 18)	13 6.1%	16 7.4%

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.
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)

Outcome Measure Data

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
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
Measure Participants	100	119
Escherichia coli (n=70, 80)	64 29.9%	75 34.6%
Klebsiella oxytoca (n=5, 5)	4 1.9%	5 2.3%
Klebsiella pneumoniae (n=22, 30)	21 9.8%	28 12.9%
Pseudomonas aeruginosa (n=14, 18)	13 6.1%	16 7.4%

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.
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)

Outcome Measure Data

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
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
Measure Participants	29	29
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.
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)

Outcome Measure Data

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
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
Measure Participants	23	24
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.
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)

Outcome Measure Data

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
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
Measure Participants	23	26
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.
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)

Outcome Measure Data

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
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
Measure Participants	17	26
Median (Full Range) [Days]	1	1.5

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ceftazidime-Avibactam Plus Metronidazole, Meropenem
	Comments
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.773
	Comments
	Method	Log Rank
	Comments

Method of Estimation	Estimation Parameter	Difference in median time (days)
	Estimated Value	0.5
	Confidence Interval	() % to
	Parameter Dispersion	Type: Value:
	Estimation Comments

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.
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)

Outcome Measure Data

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
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
Measure Participants	16	26
Median (Full Range) [Days]	1	2

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ceftazidime-Avibactam Plus Metronidazole, Meropenem
	Comments
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.598
	Comments
	Method	Log Rank
	Comments

Method of Estimation	Estimation Parameter	Difference in median time (days)
	Estimated Value	1
	Confidence Interval	() % to
	Parameter Dispersion	Type: Value:
	Estimation Comments

36. Secondary Outcome

Title	Safety and Tolerability by Incidence and Severity of Adverse Events and Serious Adverse Events and Mortality.
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)

Outcome Measure Data

Analysis Population Description
Safety analysis set: all patients who received at least 1 dose of IP

Arm/Group Title	Ceftazidime-Avibactam Plus Metronidazole	Meropenem
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
Measure Participants	215	217
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.
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)

Outcome Measure Data

Analysis Population Description
Safety analysis set: all patients who received at least 1 dose of IP

Arm/Group Title	Ceftazidime-Avibactam Plus Metronidazole	Meropenem
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
Measure Participants	215	217
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.
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)

Outcome Measure Data

Analysis Population Description
Safety analysis set: all patients who received at least 1 dose of IP

Arm/Group Title	Ceftazidime-Avibactam Plus Metronidazole	Meropenem
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
Measure Participants	215	217
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.
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)

Outcome Measure Data

Analysis Population Description
Safety analysis set: all patients who received at least 1 dose of IP

Arm/Group Title	Ceftazidime-Avibactam Plus Metronidazole	Meropenem
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
Measure Participants	215	217
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
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

Outcome Measure Data

Analysis Population Description
Safety analysis set: all patients who received at least 1 dose of IP

Arm/Group Title	Ceftazidime-Avibactam Plus Metronidazole	Meropenem
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
Measure Participants	215	217
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
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.

Outcome Measure Data

Analysis Population Description
PK analysis set

Arm/Group Title	Ceftazidime(1)	Avibactam(1)	Ceftazidime(2)	Avibactam(2)	Ceftazidime(3)	Avibactam(3)
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
Measure Participants	195	195	193	193	192	192
Geometric Mean (Full Range) [ng/mL]	60300.4	10126.9	46473.9	7289.3	9555.0	1207.2

Adverse Events

	CAZ-AVI Plus Metronidazole		Meropenem
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
Arm/Group Description	Meropenem powder for solution for infusion 1000mg
All Cause Mortality
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	CAZ-AVI Plus Metronidazole		Meropenem
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	9/215 (4.2%)		11/217 (5.1%)
Blood and lymphatic system disorders
Anaemia	1/215 (0.5%)	1	0/217 (0%)	0
Cardiac disorders
Arteriosclerosis coronary artery	1/215 (0.5%)	1	0/217 (0%)	0
Gastrointestinal disorders
Abdominal pain lower	1/215 (0.5%)	1	0/217 (0%)	0
Gastric ulcer	0/215 (0%)	0	1/217 (0.5%)	1
Gastritis	1/215 (0.5%)	1	0/217 (0%)	0
Ileus	0/215 (0%)	0	1/217 (0.5%)	1
General disorders
Impaired healing	0/215 (0%)	0	1/217 (0.5%)	1
Pyrexia	0/215 (0%)	0	1/217 (0.5%)	1
Hepatobiliary disorders
Cholangitis acute	1/215 (0.5%)	1	0/217 (0%)	0
Hepatic function abnormal	1/215 (0.5%)	1	0/217 (0%)	0
Infections and infestations
Abdominal infection	1/215 (0.5%)	1	0/217 (0%)	0
Pneumonia	0/215 (0%)	0	1/217 (0.5%)	1
Postoperative wound infection	1/215 (0.5%)	1	1/217 (0.5%)	1
Injury, poisoning and procedural complications
Incision site complication	0/215 (0%)	0	1/217 (0.5%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastasis	1/215 (0.5%)	1	0/217 (0%)	0
Non-Hodgkin's lymphoma	0/215 (0%)	0	1/217 (0.5%)	1
Psychiatric disorders
Confusional state	0/215 (0%)	0	1/217 (0.5%)	1
Renal and urinary disorders
Acute kidney injury	1/215 (0.5%)	1	1/217 (0.5%)	1
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome	1/215 (0.5%)	1	0/217 (0%)	0
Laryngeal disorder	1/215 (0.5%)	1	0/217 (0%)	0
Pneumonia aspiration	0/215 (0%)	0	1/217 (0.5%)	1
Other (Not Including Serious) Adverse Events
	CAZ-AVI Plus Metronidazole		Meropenem
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	44/215 (20.5%)		47/217 (21.7%)
Gastrointestinal disorders
Constipation	5/215 (2.3%)	5	3/217 (1.4%)	4
Diarrhoea	13/215 (6%)	14	16/217 (7.4%)	20
Nausea	18/215 (8.4%)	25	4/217 (1.8%)	4
Vomiting	5/215 (2.3%)	8	4/217 (1.8%)	5
General disorders
Pyrexia	9/215 (4.2%)	12	12/217 (5.5%)	21
Hepatobiliary disorders
Hepatic function abnormal	0/215 (0%)	0	6/217 (2.8%)	6
Nervous system disorders
Headache	3/215 (1.4%)	3	5/217 (2.3%)	5
Respiratory, thoracic and mediastinal disorders
Cough	3/215 (1.4%)	3	8/217 (3.7%)	8
Productive cough	5/215 (2.3%)	5	6/217 (2.8%)	6

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

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

Name/Title	David Wilson, Statistical Team Leader - Infection
Organization	AstraZeneca
Phone	+44 1625 517830
Email	David.Wilson2@astrazeneca.com

Responsible Party:

Pfizer

ClinicalTrials.gov Identifier:

NCT01726023

Other Study ID Numbers:

D4280C00018
2011-003893-97

First Posted:

Nov 14, 2012

Last Update Posted:

Sep 6, 2017

Last Verified:

Sep 1, 2017

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

Study Details

Study Description

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Arms and Interventions

Outcome Measures

Primary Outcome Measures

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Baseline Characteristics

Outcome Measures

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Statistical Analysis 1

Outcome Measure Data

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Statistical Analysis 1

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Statistical Analysis 1

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Adverse Events

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