Trial Outcomes & Findings for Efficacy and Safety of Ceftazidime-Avibactam (CAZ-AVI) in Chinese Participants With HAP (Including VAP) (NCT NCT04774094)

Last Updated: 2024-09-19

Results Overview

Clinical cure: participants were considered to be a success for clinical response at TOC visit if the participants were not a clinical failure at end of treatment (EOT), and the participants were alive and all signs and symptoms of pneumonia were resolved or improved to an extent that no antibacterial therapy for HAP was taken between EOT and TOC inclusive. Gram negative is abbreviated as gram -ve and gram positive as gram +ve.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

235 participants

Primary outcome timeframe

TOC visit: any day from Day 21 to 25

Results posted on

2024-09-19

Participant Flow

A total of 235 Chinese adult participants with hospital acquired pneumonia (HAP) \[including ventilator-associated pneumonia {VA}\] were enrolled.

Participant milestones

Participant milestones
Measure	Ceftazidime-Avibactam (CAZ-AVI) Participants received CAZ-AVI (Zavicefta), 2.5 grams (g) \[ceftazidime 2g + avibactam 0.5g\], intravenously (IV) as 2 hours infusion every 8 hours for a minimum of 7 days and a maximum of 14 days. Participants were followed up to maximum of 32 days after the last dose of study intervention.
Overall Study STARTED	235
Overall Study COMPLETED	191
Overall Study NOT COMPLETED	44

Reasons for withdrawal

Reasons for withdrawal
Measure	Ceftazidime-Avibactam (CAZ-AVI) Participants received CAZ-AVI (Zavicefta), 2.5 grams (g) \[ceftazidime 2g + avibactam 0.5g\], intravenously (IV) as 2 hours infusion every 8 hours for a minimum of 7 days and a maximum of 14 days. Participants were followed up to maximum of 32 days after the last dose of study intervention.
Overall Study Other	2
Overall Study Withdrawal by Subject	9
Overall Study Lost to Follow-up	7
Overall Study Lack of Efficacy	5
Overall Study Death	17
Overall Study Adverse Event	4

Baseline Characteristics

Efficacy and Safety of Ceftazidime-Avibactam (CAZ-AVI) in Chinese Participants With HAP (Including VAP)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	CAZ-AVI 1 n=235 Participants Participants received CAZ-AVI (Zavicefta), 2.5 g (ceftazidime 2g + avibactam 0.5g), IV as 2 hours infusion every 8 hours for a minimum of 7 days and a maximum of 14 days. Participants were followed up to maximum of 32 days after the last dose of study intervention.
Age, Continuous	66.0 Years STANDARD_DEVIATION 14.36 • n=5 Participants
Sex: Female, Male Female	69 Participants n=5 Participants
Sex: Female, Male Male	166 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	235 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	235 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	0 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: TOC visit: any day from Day 21 to 25

Population: cMITT: MITT subset and participants whose baseline respiratory or blood culture showed gram -ve pathogens with or without concomitant gram +ve pathogens (excluding those with gram -ve pathogens unexpected to respond to either study drug \[participants with only monomicrobial gram -ve infection: any Acinetobacter species/ Legionella species/ Stenotrophomonas maltophilia/ Elizabethkingia meningoseptica\]) or in whom no etiologic pathogens identified from respiratory or blood culture at baseline.

Outcome measures

Outcome measures
Measure	CAZ-AVI n=209 Participants Participants with HAP received CAZ-AVI, 2.5 g, IV as 2 hours infusion every 8 hours for a maximum of 14 days.
Percentage of Participants With Clinical Cure at Test of Cure (TOC) Visit: Clinical Modified Intent-to-Treat (cMITT) Population	62.7 Percentage of participants Interval 56.0 to 69.0

SECONDARY outcome

Timeframe: EOT visit: within 24 hours after the completion of the last infusion of study intervention (study treatment was a minimum of 7 days and maximum of 14 days)

Clinical cure: participants were considered to be a success for clinical response at EOT visit if the participants were alive and all signs and symptoms of pneumonia were resolved or improved such that all antibacterial therapies for HAP/ VAP were stopped. No antibacterial therapy other than those outlined by the protocol was administered for HAP prior to EOT.

Outcome measures

Outcome measures
Measure	CAZ-AVI n=209 Participants Participants with HAP received CAZ-AVI, 2.5 g, IV as 2 hours infusion every 8 hours for a maximum of 14 days.
Percentage of Participants With Clinical Cure at EOT Visit: cMITT Population	75.1 Percentage of participants Interval 68.9 to 80.6

SECONDARY outcome

Timeframe: EOT visit: within 24 hours after the completion of the last infusion of study intervention (study treatment was a minimum of 7 days and maximum of 14 days); TOC visit: any day from Day 21 to 25

Population: mMITT:MITT subset and participants with proper respiratory culture (RC) showing gram-ve pathogens,excluding participants unexpected to respond to CAZ-AVI (participants with only monomicrobial gram-ve infections:any Acinetobacter species/Legionella species/Stenotrophomonas maltophilia/Elizabethkingia meningoseptica).If baseline RC unavailable or didn't identify respiratory pathogen, but gram-ve organism causing pneumonia was identified from baseline blood cultures,participant qualified for mMITT.

Clinical cure at EOT: participants were considered to be a success for clinical response at EOT visit if the participants were alive and all signs and symptoms of pneumonia were resolved or improved such that all antibacterial therapies for HAP/VAP were stopped. No antibacterial therapy other than those outlined by the protocol was administered for HAP prior to EOT. Clinical cure at TOC: participants were considered to be a success for clinical response at TOC visit if the participants were not a clinical failure at EOT, and the participants were alive and all signs and symptoms of pneumonia were resolved or improved to an extent that no antibacterial therapy for HAP was taken between EOT and TOC inclusive.

Outcome measures

Outcome measures
Measure	CAZ-AVI n=80 Participants Participants with HAP received CAZ-AVI, 2.5 g, IV as 2 hours infusion every 8 hours for a maximum of 14 days.
Percentage of Participants With Clinical Cure at EOT and TOC Visit: Microbiological Modified Intent-to-Treat (mMITT) Population EOT visit	70.0 Percentage of participants Interval 59.4 to 79.2
Percentage of Participants With Clinical Cure at EOT and TOC Visit: Microbiological Modified Intent-to-Treat (mMITT) Population TOC visit	57.5 Percentage of participants Interval 46.6 to 67.9

SECONDARY outcome

Population: mMITT:MITT subset and participants with proper RC showing gram-ve pathogens,excluding participants unexpected to respond to CAZ-AVI (participants with only monomicrobial gram-ve infections:any Acinetobacter species/Legionella species/Stenotrophomonas maltophilia/Elizabethkingia meningoseptica).If baseline RC unavailable or didn't identify respiratory pathogen, but gram-ve organism causing pneumonia was identified from baseline blood cultures,participant qualified for mMITT.

For participants from whom only 1 causative pathogen is isolated, the overall microbiological response assessment was based on the microbiological response assessment for that pathogen. For participants from whom more than 1 baseline pathogen was isolated, the overall microbiological response assessment was "favorable" only if the microbiological response assessment for each of the baseline pathogens isolated was "favorable". Favorable microbiological response included eradication (an adequate source specimen demonstrated absence of the original baseline pathogen) and presumed eradication (an adequate source specimen was not available to culture and the participant was assessed as a clinical cure). In this outcome measure percentage of participants with favorable per-participant microbiological response are recorded.

Outcome measures

Outcome measures
Measure	CAZ-AVI n=80 Participants Participants with HAP received CAZ-AVI, 2.5 g, IV as 2 hours infusion every 8 hours for a maximum of 14 days.
Percentage of Participants With Favorable Per-Participant Microbiological Response at the EOT and TOC Visits: mMITT Population EOT visit	77.5 Percentage of participants Interval 67.5 to 85.6
Percentage of Participants With Favorable Per-Participant Microbiological Response at the EOT and TOC Visits: mMITT Population TOC visit	51.3 Percentage of participants Interval 40.4 to 62.0

SECONDARY outcome

Population: mMITT analysis set evaluated. All participants reported under "Number of Participants Analyzed" contributed data to the table; however, may not have evaluable data for every row. Here, "Number Analyzed" signifies number of participants in mMITT analysis set evaluable for specified pathogens and visits.

Favorable microbiological response included eradication (an adequate source specimen demonstrated absence of the original baseline pathogen) and presumed eradication (an adequate source specimen was not available to culture and the participant was assessed as a clinical cure). In this outcome measure percentage of participants with favorable per-pathogen microbiological response are recorded.

Outcome measures

Outcome measures
Measure	CAZ-AVI n=80 Participants Participants with HAP received CAZ-AVI, 2.5 g, IV as 2 hours infusion every 8 hours for a maximum of 14 days.
Percentage of Participants With Favorable Per-Pathogen Microbiological Response at the EOT and TOC Visits: mMITT Population TOC visit: Morganella morganii	100 Percentage of participants Interval 14.7 to 100.0
Percentage of Participants With Favorable Per-Pathogen Microbiological Response at the EOT and TOC Visits: mMITT Population TOC visit: Proteus mirabilis	66.7 Percentage of participants Interval 17.7 to 96.1
Percentage of Participants With Favorable Per-Pathogen Microbiological Response at the EOT and TOC Visits: mMITT Population EOT visit: Enterobacter cloacae	33.3 Percentage of participants Interval 3.9 to 82.3
Percentage of Participants With Favorable Per-Pathogen Microbiological Response at the EOT and TOC Visits: mMITT Population EOT visit: Escherichia coli	100 Percentage of participants Interval 62.1 to 100.0
Percentage of Participants With Favorable Per-Pathogen Microbiological Response at the EOT and TOC Visits: mMITT Population EOT visit: Klebsiella aerogenes	80.0 Percentage of participants Interval 37.1 to 97.7
Percentage of Participants With Favorable Per-Pathogen Microbiological Response at the EOT and TOC Visits: mMITT Population EOT visit: Klebsiella pneumoniae	77.6 Percentage of participants Interval 64.5 to 87.4
Percentage of Participants With Favorable Per-Pathogen Microbiological Response at the EOT and TOC Visits: mMITT Population EOT visit: Klebsiella variicola	100 Percentage of participants Interval 14.7 to 100.0
Percentage of Participants With Favorable Per-Pathogen Microbiological Response at the EOT and TOC Visits: mMITT Population EOT visit: Morganella morganii	100 Percentage of participants Interval 14.7 to 100.0
Percentage of Participants With Favorable Per-Pathogen Microbiological Response at the EOT and TOC Visits: mMITT Population EOT visit: Proteus mirabilis	100 Percentage of participants Interval 46.4 to 100.0
Percentage of Participants With Favorable Per-Pathogen Microbiological Response at the EOT and TOC Visits: mMITT Population EOT visit: Proteus vulgaris	100 Percentage of participants Interval 14.7 to 100.0
Percentage of Participants With Favorable Per-Pathogen Microbiological Response at the EOT and TOC Visits: mMITT Population EOT visit: Providencia rettgeri	100 Percentage of participants Interval 14.7 to 100.0
Percentage of Participants With Favorable Per-Pathogen Microbiological Response at the EOT and TOC Visits: mMITT Population EOT visit: Providencia stuartii	100 Percentage of participants Interval 14.7 to 100.0
Percentage of Participants With Favorable Per-Pathogen Microbiological Response at the EOT and TOC Visits: mMITT Population EOT visit: Serratia marcescens	100 Percentage of participants Interval 14.7 to 100.0
Percentage of Participants With Favorable Per-Pathogen Microbiological Response at the EOT and TOC Visits: mMITT Population EOT visit: Acinetobacter baumannii	71.4 Percentage of participants Interval 35.2 to 93.5
Percentage of Participants With Favorable Per-Pathogen Microbiological Response at the EOT and TOC Visits: mMITT Population EOT visit: Haemophilus influenzae	100 Percentage of participants Interval 55.5 to 100.0
Percentage of Participants With Favorable Per-Pathogen Microbiological Response at the EOT and TOC Visits: mMITT Population EOT visit: Moraxella catarrhalis	0 Percentage of participants Interval 0.0 to 85.3
Percentage of Participants With Favorable Per-Pathogen Microbiological Response at the EOT and TOC Visits: mMITT Population EOT visit: Pseudomonas aeruginosa	75.0 Percentage of participants Interval 50.9 to 90.9
Percentage of Participants With Favorable Per-Pathogen Microbiological Response at the EOT and TOC Visits: mMITT Population EOT visit: Stenotrophomonas maltophilia	50.0 Percentage of participants Interval 6.1 to 93.9
Percentage of Participants With Favorable Per-Pathogen Microbiological Response at the EOT and TOC Visits: mMITT Population EOT visit: Enterococcus faecium	100 Percentage of participants Interval 14.7 to 100.0
Percentage of Participants With Favorable Per-Pathogen Microbiological Response at the EOT and TOC Visits: mMITT Population EOT visit: Staphylococcus aureus	57.1 Percentage of participants Interval 23.5 to 86.1
Percentage of Participants With Favorable Per-Pathogen Microbiological Response at the EOT and TOC Visits: mMITT Population EOT visit: Staphylococcus hominis	100 Percentage of participants Interval 14.7 to 100.0
Percentage of Participants With Favorable Per-Pathogen Microbiological Response at the EOT and TOC Visits: mMITT Population TOC visit: Enterobacter cloacae	33.3 Percentage of participants Interval 3.9 to 82.3
Percentage of Participants With Favorable Per-Pathogen Microbiological Response at the EOT and TOC Visits: mMITT Population TOC visit: Escherichia coli	100 Percentage of participants Interval 62.1 to 100.0
Percentage of Participants With Favorable Per-Pathogen Microbiological Response at the EOT and TOC Visits: mMITT Population TOC visit: Klebsiella aerogenes	80.0 Percentage of participants Interval 37.1 to 97.7
Percentage of Participants With Favorable Per-Pathogen Microbiological Response at the EOT and TOC Visits: mMITT Population TOC visit: Klebsiella pneumoniae	53.1 Percentage of participants Interval 39.2 to 66.5
Percentage of Participants With Favorable Per-Pathogen Microbiological Response at the EOT and TOC Visits: mMITT Population TOC visit: Klebsiella variicola	100 Percentage of participants Interval 14.7 to 100.0
Percentage of Participants With Favorable Per-Pathogen Microbiological Response at the EOT and TOC Visits: mMITT Population TOC visit: Proteus vulgaris	100 Percentage of participants Interval 14.7 to 100.0
Percentage of Participants With Favorable Per-Pathogen Microbiological Response at the EOT and TOC Visits: mMITT Population TOC visit: Providencia rettgeri	100 Percentage of participants Interval 14.7 to 100.0
Percentage of Participants With Favorable Per-Pathogen Microbiological Response at the EOT and TOC Visits: mMITT Population TOC visit: Providencia stuartii	100 Percentage of participants Interval 14.7 to 100.0
Percentage of Participants With Favorable Per-Pathogen Microbiological Response at the EOT and TOC Visits: mMITT Population TOC visit: Serratia marcescens	100 Percentage of participants Interval 14.7 to 100.0
Percentage of Participants With Favorable Per-Pathogen Microbiological Response at the EOT and TOC Visits: mMITT Population TOC visit: Acinetobacter baumannii	42.9 Percentage of participants Interval 13.9 to 76.5
Percentage of Participants With Favorable Per-Pathogen Microbiological Response at the EOT and TOC Visits: mMITT Population TOC visit: Haemophilus influenzae	100 Percentage of participants Interval 55.5 to 100.0
Percentage of Participants With Favorable Per-Pathogen Microbiological Response at the EOT and TOC Visits: mMITT Population TOC visit: Moraxella catarrhalis	0 Percentage of participants Interval 0.0 to 85.3
Percentage of Participants With Favorable Per-Pathogen Microbiological Response at the EOT and TOC Visits: mMITT Population TOC visit: Pseudomonas aeruginosa	37.5 Percentage of participants Interval 17.4 to 61.7
Percentage of Participants With Favorable Per-Pathogen Microbiological Response at the EOT and TOC Visits: mMITT Population TOC visit: Stenotrophomonas maltophilia	0 Percentage of participants Interval 0.0 to 66.7
Percentage of Participants With Favorable Per-Pathogen Microbiological Response at the EOT and TOC Visits: mMITT Population TOC visit: Enterococcus faecium	100 Percentage of participants Interval 14.7 to 100.0
Percentage of Participants With Favorable Per-Pathogen Microbiological Response at the EOT and TOC Visits: mMITT Population TOC visit: Staphylococcus aureus	42.9 Percentage of participants Interval 13.9 to 76.5
Percentage of Participants With Favorable Per-Pathogen Microbiological Response at the EOT and TOC Visits: mMITT Population TOC visit: Staphylococcus hominis	100 Percentage of participants Interval 14.7 to 100.0

SECONDARY outcome

Population: mMITT analysis set evaluated. Here, "Overall Number of Participants Analyzed" signifies number of participants who were evaluable for this outcome measure, i.e. participants in mMITT analysis set that with gram-negative baseline pathogens resistant to ceftazidime.

Outcome measures

Outcome measures
Measure	CAZ-AVI n=30 Participants Participants with HAP received CAZ-AVI, 2.5 g, IV as 2 hours infusion every 8 hours for a maximum of 14 days.
Percentage of Participants With Clinical Cure at the EOT and TOC Visits in Participants With Gram-negative Baseline Pathogens Resistant to Ceftazidime: mMITT Population EOT visit	63.3 Percentage of participants Interval 45.5 to 78.7
Percentage of Participants With Clinical Cure at the EOT and TOC Visits in Participants With Gram-negative Baseline Pathogens Resistant to Ceftazidime: mMITT Population TOC visit	53.3 Percentage of participants Interval 35.9 to 70.2

SECONDARY outcome

Outcome measures

Outcome measures
Measure	CAZ-AVI n=30 Participants Participants with HAP received CAZ-AVI, 2.5 g, IV as 2 hours infusion every 8 hours for a maximum of 14 days.
Percentage of Participants With Favorable Per-Participant Microbiologic Response at the EOT and TOC Visits in Participants With Gram-negative Baseline Pathogens Resistant to Ceftazidime: mMITT Population EOT visit	73.3 Percentage of participants Interval 55.9 to 86.5
Percentage of Participants With Favorable Per-Participant Microbiologic Response at the EOT and TOC Visits in Participants With Gram-negative Baseline Pathogens Resistant to Ceftazidime: mMITT Population TOC visit	46.7 Percentage of participants Interval 29.8 to 64.1

SECONDARY outcome

Timeframe: TOC visit: any day from Day 21 to 25; Day 28

Outcome measures

Outcome measures
Measure	CAZ-AVI n=209 Participants Participants with HAP received CAZ-AVI, 2.5 g, IV as 2 hours infusion every 8 hours for a maximum of 14 days.
Percentage of Participants With Death Due to Any Cause at the TOC Visit and at Day 28 Visit: cMITT Population TOC visit	5.7 Percentage of participants Interval 3.2 to 9.5
Percentage of Participants With Death Due to Any Cause at the TOC Visit and at Day 28 Visit: cMITT Population Day 28 visit	5.7 Percentage of participants Interval 3.2 to 9.5

SECONDARY outcome

Timeframe: TOC visit: any day from Day 21 to 25; Day 28

Outcome measures

Outcome measures
Measure	CAZ-AVI n=80 Participants Participants with HAP received CAZ-AVI, 2.5 g, IV as 2 hours infusion every 8 hours for a maximum of 14 days.
Percentage of Participants With Death Due to Any Cause at the TOC Visit and at Day 28 Visit: mMITT Population TOC visit	7.5 Percentage of participants Interval 3.2 to 14.8
Percentage of Participants With Death Due to Any Cause at the TOC Visit and at Day 28 Visit: mMITT Population Day 28 visit	7.5 Percentage of participants Interval 3.2 to 14.8

SECONDARY outcome

Timeframe: Day 1 up to 32 days after last dose of CAZ-AVI (maximum up to 46 days; maximum treatment duration was of 14 days)

Population: SAS included all participants who had taken at least 1 dose of study intervention.

An AE was any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. AEs included both SAEs and all non-SAEs that occurred in the study. TEAEs were AEs between first dose of study treatment and up to 32 days post last dose that were absent before treatment or that worsened relative to pretreatment state.

Outcome measures

Outcome measures
Measure	CAZ-AVI n=235 Participants Participants with HAP received CAZ-AVI, 2.5 g, IV as 2 hours infusion every 8 hours for a maximum of 14 days.
Number of Participants With Treatment Emergent Adverse Events (TEAEs)	204 Participants

SECONDARY outcome

Timeframe: Day 1 up to 32 days after last dose of CAZ-AVI (maximum up to 46 days; maximum treatment duration was of 14 days)

Population: SAS included all participants who had taken at least 1 dose of study intervention. Here "Number of Participants Analyzed" includes number of participants evaluable for laboratory abnormalities.

Hematology: Hemoglobin (Hg), hematocrit, erythrocytes: less than (\<)0.8\*lower limit of normal (LLN) \& change (chg) more than (\>)20% decrease (dec); platelets: \<0.65\*LLN \& chg \>50% dec \&, \>1.5\* upper limit of normal (ULN) \& chg \>100% increase (inc); leukocytes: \<0.65\*LLN \& chg \>60% dec \&, \>1.6\*ULN \& chg \>100% inc; lymphocytes, \<0.25\*LLN \& chg \>75% dec; neutrophils: \<0.65\*LLN \& chg \>75% dec \&, \>1.6\*ULN \& chg \>100% inc; basophils, monocytes: \>4.0\* ULN \& chg \>300% inc. Clinical chemistry: bilirubin: \>2.0\*ULN \& chg \>150% inc; aspartate aminotransferase (AT) \& Alanine AT: \>3.0\*ULN \& chg \>200% inc; alkaline phosphatase \<0.5\*LLN \& chg \>80% dec \& \>2.0\*ULN \& chg \>100% inc; creatinine: \>2.0\*ULN \& \>chg 100% inc; sodium: \<0.85\*LLN \& chg \>10% dec \& \>1.1\*ULN \& chg \>10% inc; potassium \& chloride: \<0.8\*LLN \& chg \>20% dec \& \>1.2\*ULN \& chg \>20% dec; calcium: \<0.7\*LLN \& chg \>30% dec \& bicarbonate: \<0.7\*LLN \& chg \>40% dec. Clinical significance was judged by investigator.

Outcome measures

Outcome measures
Measure	CAZ-AVI n=234 Participants Participants with HAP received CAZ-AVI, 2.5 g, IV as 2 hours infusion every 8 hours for a maximum of 14 days.
Number of Participants With Clinically Significant Post-Baseline Laboratory Test Abnormalities	102 Participants

SECONDARY outcome

Timeframe: Day 1 up to 32 days after last dose of CAZ-AVI (maximum up to 46 days; maximum treatment duration was of 14 days)

Population: SAS included all participants who had taken at least 1 dose of study intervention.

Vital signs included diastolic blood pressure (millimeters of mercury \[mmHg\]); pulse rate (beats per minute \[bpm\]) and systolic blood pressure (mmHg). Pre-defined criteria: Diastolic blood pressure: Value \<50 mmHg, Diastolic blood pressure: Change more than or equal to (\>=) 20 mmHg increase, Diastolic blood pressure: Change \>= 20 mmHg decrease, Pulse rate: Value \<40 bpm, Pulse rate: Value \>120 bpm, Systolic blood pressure: Value \<90 mmHg, Systolic blood pressure: Change \>= 30 mmHg increase, Systolic blood pressure: Change \>= 30 mmHg decrease. One participant could have more than one vital sign abnormality.

Outcome measures

Outcome measures
Measure	CAZ-AVI n=235 Participants Participants with HAP received CAZ-AVI, 2.5 g, IV as 2 hours infusion every 8 hours for a maximum of 14 days.
Number of Participants With Vital Signs Data According to Pre-defined Criteria Diastolic blood pressure: Change >=20 mmHg increase	72 Participants
Number of Participants With Vital Signs Data According to Pre-defined Criteria Diastolic blood pressure: Change >= 20 mmHg decrease	54 Participants
Number of Participants With Vital Signs Data According to Pre-defined Criteria Pulse rate: Value <40 bpm	1 Participants
Number of Participants With Vital Signs Data According to Pre-defined Criteria Pulse rate: Value >120 bpm	31 Participants
Number of Participants With Vital Signs Data According to Pre-defined Criteria Systolic blood pressure: Value <90 mmHg	11 Participants
Number of Participants With Vital Signs Data According to Pre-defined Criteria Systolic blood pressure: Change >= 30 mmHg increase	61 Participants
Number of Participants With Vital Signs Data According to Pre-defined Criteria Systolic blood pressure: Change >= 30 mmHg decrease	64 Participants
Number of Participants With Vital Signs Data According to Pre-defined Criteria Diastolic blood pressure: <50 mmHg	18 Participants

Adverse Events

CAZ-AVI

Serious events: 35 serious events

Other events: 43 other events

Deaths: 17 deaths

Serious adverse events

Serious adverse events
Measure	CAZ-AVI n=235 participants at risk Participants received CAZ-AVI (Zavicefta), 2.5 g (ceftazidime 2g + avibactam 0.5g), IV as 2 hours infusion every 8 hours for a minimum of 7 days and a maximum of 14 days. Participants were followed up to maximum of 32 days after the last dose of study intervention.
Cardiac disorders Cardiac arrest	0.43% 1/235 • Day 1 up to 32 days after last dose of CAZ-AVI (maximum up to 46 days; maximum treatment duration was of 14 days) Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Non-SAES are reported at 5% threshold.
Cardiac disorders Cardio-respiratory arrest	0.43% 1/235 • Day 1 up to 32 days after last dose of CAZ-AVI (maximum up to 46 days; maximum treatment duration was of 14 days) Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Non-SAES are reported at 5% threshold.
Cardiac disorders Cardiogenic shock	0.43% 1/235 • Day 1 up to 32 days after last dose of CAZ-AVI (maximum up to 46 days; maximum treatment duration was of 14 days) Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Non-SAES are reported at 5% threshold.
Cardiac disorders Myocardial infarction	0.43% 1/235 • Day 1 up to 32 days after last dose of CAZ-AVI (maximum up to 46 days; maximum treatment duration was of 14 days) Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Non-SAES are reported at 5% threshold.
Gastrointestinal disorders Ileus	0.43% 1/235 • Day 1 up to 32 days after last dose of CAZ-AVI (maximum up to 46 days; maximum treatment duration was of 14 days) Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Non-SAES are reported at 5% threshold.
General disorders Death	0.43% 1/235 • Day 1 up to 32 days after last dose of CAZ-AVI (maximum up to 46 days; maximum treatment duration was of 14 days) Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Non-SAES are reported at 5% threshold.
General disorders Effusion	0.43% 1/235 • Day 1 up to 32 days after last dose of CAZ-AVI (maximum up to 46 days; maximum treatment duration was of 14 days) Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Non-SAES are reported at 5% threshold.
General disorders Multiple organ dysfunction syndrome	0.43% 1/235 • Day 1 up to 32 days after last dose of CAZ-AVI (maximum up to 46 days; maximum treatment duration was of 14 days) Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Non-SAES are reported at 5% threshold.
General disorders Pyrexia	0.43% 1/235 • Day 1 up to 32 days after last dose of CAZ-AVI (maximum up to 46 days; maximum treatment duration was of 14 days) Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Non-SAES are reported at 5% threshold.
General disorders Sudden cardiac death	0.43% 1/235 • Day 1 up to 32 days after last dose of CAZ-AVI (maximum up to 46 days; maximum treatment duration was of 14 days) Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Non-SAES are reported at 5% threshold.
Hepatobiliary disorders Hepatic function abnormal	0.85% 2/235 • Day 1 up to 32 days after last dose of CAZ-AVI (maximum up to 46 days; maximum treatment duration was of 14 days) Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Non-SAES are reported at 5% threshold.
Hepatobiliary disorders Liver injury	0.85% 2/235 • Day 1 up to 32 days after last dose of CAZ-AVI (maximum up to 46 days; maximum treatment duration was of 14 days) Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Non-SAES are reported at 5% threshold.
Immune system disorders Anti-neutrophil cytoplasmic antibody positive vasculitis	0.43% 1/235 • Day 1 up to 32 days after last dose of CAZ-AVI (maximum up to 46 days; maximum treatment duration was of 14 days) Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Non-SAES are reported at 5% threshold.
Infections and infestations Fungaemia	0.43% 1/235 • Day 1 up to 32 days after last dose of CAZ-AVI (maximum up to 46 days; maximum treatment duration was of 14 days) Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Non-SAES are reported at 5% threshold.
Infections and infestations Intracranial infection	0.43% 1/235 • Day 1 up to 32 days after last dose of CAZ-AVI (maximum up to 46 days; maximum treatment duration was of 14 days) Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Non-SAES are reported at 5% threshold.
Infections and infestations Pneumonia	3.0% 7/235 • Day 1 up to 32 days after last dose of CAZ-AVI (maximum up to 46 days; maximum treatment duration was of 14 days) Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Non-SAES are reported at 5% threshold.
Infections and infestations Pneumonia aspiration	0.43% 1/235 • Day 1 up to 32 days after last dose of CAZ-AVI (maximum up to 46 days; maximum treatment duration was of 14 days) Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Non-SAES are reported at 5% threshold.
Infections and infestations Pneumonia fungal	0.43% 1/235 • Day 1 up to 32 days after last dose of CAZ-AVI (maximum up to 46 days; maximum treatment duration was of 14 days) Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Non-SAES are reported at 5% threshold.
Infections and infestations Puncture site infection	0.43% 1/235 • Day 1 up to 32 days after last dose of CAZ-AVI (maximum up to 46 days; maximum treatment duration was of 14 days) Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Non-SAES are reported at 5% threshold.
Infections and infestations Septic shock	0.43% 1/235 • Day 1 up to 32 days after last dose of CAZ-AVI (maximum up to 46 days; maximum treatment duration was of 14 days) Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Non-SAES are reported at 5% threshold.
Infections and infestations Urinary tract infection	0.43% 1/235 • Day 1 up to 32 days after last dose of CAZ-AVI (maximum up to 46 days; maximum treatment duration was of 14 days) Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Non-SAES are reported at 5% threshold.
Injury, poisoning and procedural complications Brain herniation	0.85% 2/235 • Day 1 up to 32 days after last dose of CAZ-AVI (maximum up to 46 days; maximum treatment duration was of 14 days) Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Non-SAES are reported at 5% threshold.
Injury, poisoning and procedural complications Wound haemorrhage	0.43% 1/235 • Day 1 up to 32 days after last dose of CAZ-AVI (maximum up to 46 days; maximum treatment duration was of 14 days) Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Non-SAES are reported at 5% threshold.
Nervous system disorders Cerebral haemorrhage	0.43% 1/235 • Day 1 up to 32 days after last dose of CAZ-AVI (maximum up to 46 days; maximum treatment duration was of 14 days) Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Non-SAES are reported at 5% threshold.
Nervous system disorders Hypoxic-ischaemic encephalopathy	0.85% 2/235 • Day 1 up to 32 days after last dose of CAZ-AVI (maximum up to 46 days; maximum treatment duration was of 14 days) Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Non-SAES are reported at 5% threshold.
Nervous system disorders Subdural effusion	0.43% 1/235 • Day 1 up to 32 days after last dose of CAZ-AVI (maximum up to 46 days; maximum treatment duration was of 14 days) Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Non-SAES are reported at 5% threshold.
Renal and urinary disorders Acute kidney injury	0.43% 1/235 • Day 1 up to 32 days after last dose of CAZ-AVI (maximum up to 46 days; maximum treatment duration was of 14 days) Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Non-SAES are reported at 5% threshold.
Respiratory, thoracic and mediastinal disorders Asphyxia	0.85% 2/235 • Day 1 up to 32 days after last dose of CAZ-AVI (maximum up to 46 days; maximum treatment duration was of 14 days) Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Non-SAES are reported at 5% threshold.
Respiratory, thoracic and mediastinal disorders Respiratory failure	1.7% 4/235 • Day 1 up to 32 days after last dose of CAZ-AVI (maximum up to 46 days; maximum treatment duration was of 14 days) Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Non-SAES are reported at 5% threshold.

Other adverse events

Other adverse events
Measure	CAZ-AVI n=235 participants at risk Participants received CAZ-AVI (Zavicefta), 2.5 g (ceftazidime 2g + avibactam 0.5g), IV as 2 hours infusion every 8 hours for a minimum of 7 days and a maximum of 14 days. Participants were followed up to maximum of 32 days after the last dose of study intervention.
Gastrointestinal disorders Diarrhoea	7.2% 17/235 • Day 1 up to 32 days after last dose of CAZ-AVI (maximum up to 46 days; maximum treatment duration was of 14 days) Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Non-SAES are reported at 5% threshold.
Hepatobiliary disorders Hepatic function abnormal	11.5% 27/235 • Day 1 up to 32 days after last dose of CAZ-AVI (maximum up to 46 days; maximum treatment duration was of 14 days) Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Non-SAES are reported at 5% threshold.

Additional Information

Pfizer ClinicalTrials.gov Call Center

Pfizer Inc.

Phone: 1-800-718-1021

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
Publication restrictions are in place

Restriction type: OTHER