Trial Outcomes & Findings for Efficacy and Safety of CAZ-AVI in the Treatment of Infections Due to Carbapenem-resistant G- Pathogens in Chinese Adults (NCT NCT04882085)

NCT ID: NCT04882085

Last Updated: 2024-10-21

Results Overview

Clinical cure was defined as improvement in baseline signs and symptoms such that no further antimicrobial treatment was required for the index infection (i.e, complicated intra-abdominal infection \[cIAI\], complicated urinary-tract infection \[cUTI\], hospital-acquired pneumonia/ventilator-associated pneumonia \[HAP/VAP\] or bloodstream infection \[BSI\]) after study treatment. Also, for cIAI participants, no unplanned drainage or surgical intervention was necessary since the initial procedure. The clinical response was assessed by the independent adjudication committee. 95 percent (%) confidence interval (CI) was calculated using Jeffrey's method.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

60 participants

Primary outcome timeframe

At TOC visit (From Day 21 up to Day 24)

Results posted on

2024-10-21

Participant Flow

A total of 64 participants were screened of which 3 participants failed screening and 1 participant was not randomized in the study. A total of 60 participants were enrolled and randomized in the study.

Participant milestones

Participant milestones
Measure	Ceftazidime-Avibactam Participants with confirmed carbapenem-resistant Gram-negative pathogens infection received Ceftazidime-Avibactam (CAZ-AVI) 2.5 grams (g) (2 g ceftazidime + 0.5 g avibactam) administered intravenously (IV) as 2-hour infusion every 8 hours (q8h) for 14 days.	Best Available Treatment Participants with confirmed carbapenem-resistant Gram-negative pathogens infection received best available treatment (BAT) based on investigative site practice and local epidemiology and guideline for 14 days.
Overall Study STARTED	31	29
Overall Study Safety Analysis Set	30	29
Overall Study COMPLETED	24	17
Overall Study NOT COMPLETED	7	12

Reasons for withdrawal

Reasons for withdrawal
Measure	Ceftazidime-Avibactam Participants with confirmed carbapenem-resistant Gram-negative pathogens infection received Ceftazidime-Avibactam (CAZ-AVI) 2.5 grams (g) (2 g ceftazidime + 0.5 g avibactam) administered intravenously (IV) as 2-hour infusion every 8 hours (q8h) for 14 days.	Best Available Treatment Participants with confirmed carbapenem-resistant Gram-negative pathogens infection received best available treatment (BAT) based on investigative site practice and local epidemiology and guideline for 14 days.
Overall Study Death	6	9
Overall Study Withdrawal by Subject	0	3
Overall Study Randomized not treated	1	0

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Ceftazidime-Avibactam n=30 Participants Participants with confirmed carbapenem-resistant Gram-negative pathogens infection received CAZ-AVI 2.5 g (2 g ceftazidime + 0.5 g avibactam) administered IV as 2-hour infusion q8h for 14 days.	Best Available Treatment n=29 Participants Participants with confirmed carbapenem-resistant Gram-negative pathogens infection received BAT based on investigative site practice and local epidemiology and guideline for 14 days.	Total n=59 Participants Total of all reporting groups
Age, Customized 18-44 years	1 Participants n=30 Participants	2 Participants n=29 Participants	3 Participants n=59 Participants
Age, Customized 45-64 years	8 Participants n=30 Participants	8 Participants n=29 Participants	16 Participants n=59 Participants
Age, Customized Greater than equal to (>=) 65 years	21 Participants n=30 Participants	19 Participants n=29 Participants	40 Participants n=59 Participants
Sex: Female, Male Female	8 Participants n=30 Participants	9 Participants n=29 Participants	17 Participants n=59 Participants
Sex: Female, Male Male	22 Participants n=30 Participants	20 Participants n=29 Participants	42 Participants n=59 Participants
Race and Ethnicity Not Collected	—	—	0 Participants Race and Ethnicity were not collected from any participant.

PRIMARY outcome

Timeframe: At TOC visit (From Day 21 up to Day 24)

Population: mMITT analysis set (subset of ITT analysis set) included all participants who met minimum disease requirements and received any amount of study therapy, had at least 1 carbapenem-resistant Gram-negative pathogen in an adequate initial/pre-study culture. Participants with inherently resistant pathogens (monomicrobial infections due to any Acinetobacter species) were excluded from mMITT analysis set.

Outcome measures

Outcome measures
Measure	Ceftazidime-Avibactam n=27 Participants Participants with confirmed carbapenem-resistant Gram-negative pathogens infection received CAZ-AVI 2.5 g (2 g ceftazidime + 0.5 g avibactam) administered IV as 2-hour infusion q8h for 14 days.	Best Available Treatment n=27 Participants Participants with confirmed carbapenem-resistant Gram-negative pathogens infection received BAT based on investigative site practice and local epidemiology and guideline for 14 days.
Percentage of Participants With Clinical Cure at Test of Cure (TOC) Visit - Microbiologically Modified Intent-to-Treat (mMITT) Analysis Set	59.3 Percentage of participants Interval 40.6 to 76.1	25.9 Percentage of participants Interval 12.4 to 44.3

SECONDARY outcome

Timeframe: At TOC visit (From Day 21 up to Day 24)

Population: ME analysis set was evaluated.

Clinical cure: improvement in baseline signs and symptoms such that no further antimicrobial treatment was required for index infection (i.e. cIAI, cUTI, HAP/VAP or BSI) after study treatment. Also, for cIAI participants, no unplanned drainage or surgical intervention was necessary since initial procedure. 95% CI based on Jeffrey's method. ME analysis set (sub-set of mMITT): participants who received 3 days of study intervention, or received study intervention for \>=48 hours with \>= 80% compliance, or for \<48 hours before discontinuation due to adverse event, no concomitant antibiotics against baseline carbapenem-resistant gram negative pathogens between first dose and TOC (excluding participants with failed study therapy requiring additional antibiotics), had baseline organisms genetically confirmed by central microbiological testing, no indeterminate clinical outcome at end of treatment (EOT) or TOC visits, no important protocol deviations that affect assessment of efficacy.

Outcome measures

Outcome measures
Measure	Ceftazidime-Avibactam n=14 Participants Participants with confirmed carbapenem-resistant Gram-negative pathogens infection received CAZ-AVI 2.5 g (2 g ceftazidime + 0.5 g avibactam) administered IV as 2-hour infusion q8h for 14 days.	Best Available Treatment n=19 Participants Participants with confirmed carbapenem-resistant Gram-negative pathogens infection received BAT based on investigative site practice and local epidemiology and guideline for 14 days.
Percentage of Participants With Clinical Cure at TOC Visit - Microbiologically Evaluable (ME) Analysis Set	78.6 Percentage of participants Interval 53.1 to 93.6	26.3 Percentage of participants Interval 10.8 to 48.4

SECONDARY outcome

Timeframe: At EOT visit (up to 24 hours after the last infusion on Day 14)

Clinical cure was defined as improvement in baseline signs and symptoms such that no further antimicrobial treatment was required for the index infection (i.e., cIAI, cUTI, HAP/VAP or BSI) after study treatment. Also, for cIAI participants, no unplanned drainage or surgical intervention was necessary since the initial procedure. The clinical response was assessed by the independent adjudication committee. 95% CI was calculated using Jeffrey's method.

Outcome measures

Outcome measures
Measure	Ceftazidime-Avibactam n=27 Participants Participants with confirmed carbapenem-resistant Gram-negative pathogens infection received CAZ-AVI 2.5 g (2 g ceftazidime + 0.5 g avibactam) administered IV as 2-hour infusion q8h for 14 days.	Best Available Treatment n=27 Participants Participants with confirmed carbapenem-resistant Gram-negative pathogens infection received BAT based on investigative site practice and local epidemiology and guideline for 14 days.
Percentage of Participants With Clinical Cure at End of Treatment (EOT) Visit -mMITT Analysis Set	66.7 Percentage of participants Interval 47.9 to 82.1	29.6 Percentage of participants Interval 15.1 to 48.2

SECONDARY outcome

Timeframe: At EOT visit (up to 24 hours after the last infusion on Day 14)

Population: ME analysis set was evaluated.

Clinical cure: improvement in baseline signs and symptoms such that no further antimicrobial treatment was required for index infection (i.e., cIAI, cUTI, HAP/VAP or BSI) after study treatment. Also, for cIAI participants, no unplanned drainage or surgical intervention was necessary since initial procedure. 95% CI based on Jeffrey's method. ME analysis set (sub-set of mMITT): participants who received 3 days of study intervention, or received study intervention for \>=48 hours with \>= 80% compliance, or for \<48 hours before discontinuation due to adverse event, no concomitant antibiotics against baseline carbapenem-resistant gram negative pathogens between first dose and TOC (excluding participants with failed study therapy requiring additional antibiotics), had baseline organisms genetically confirmed by central microbiological testing, no indeterminate clinical outcome at EOT or TOC visits, no important protocol deviations that affect assessment of efficacy.

Outcome measures

Outcome measures
Measure	Ceftazidime-Avibactam n=14 Participants Participants with confirmed carbapenem-resistant Gram-negative pathogens infection received CAZ-AVI 2.5 g (2 g ceftazidime + 0.5 g avibactam) administered IV as 2-hour infusion q8h for 14 days.	Best Available Treatment n=19 Participants Participants with confirmed carbapenem-resistant Gram-negative pathogens infection received BAT based on investigative site practice and local epidemiology and guideline for 14 days.
Percentage of Participants With Clinical Cure at EOT Visit - ME Analysis Set	78.6 Percentage of participants Interval 53.1 to 93.6	31.6 Percentage of participants Interval 14.4 to 53.9

SECONDARY outcome

Timeframe: At TOC visit (From Day 21 up to Day 24)

Favorable microbiological response was defined as eradication or presumed eradication. Eradication was defined as absence (or urine quantification \<10\^3 colony forming units per milliliter \[CFU/mL\] for cUTI participants) of causative pathogen from an appropriately obtained specimen at the site of infection. Presumed eradication was defined as repeat culture of specimens were not performed/ clinically indicated in a participant who had a clinical response of cure (specific to cIAI and HAP/VAP participants). 95% CI was calculated using Jeffrey's method.

Outcome measures

Outcome measures
Measure	Ceftazidime-Avibactam n=27 Participants Participants with confirmed carbapenem-resistant Gram-negative pathogens infection received CAZ-AVI 2.5 g (2 g ceftazidime + 0.5 g avibactam) administered IV as 2-hour infusion q8h for 14 days.	Best Available Treatment n=27 Participants Participants with confirmed carbapenem-resistant Gram-negative pathogens infection received BAT based on investigative site practice and local epidemiology and guideline for 14 days.
Percentage of Participants With Favorable Per-Participant Microbiological Response at TOC Visit - mMITT Analysis Set	59.3 Percentage of participants Interval 40.6 to 76.1	25.9 Percentage of participants Interval 12.4 to 44.3

SECONDARY outcome

Timeframe: At TOC visit (From Day 21 up to Day 24)

Population: ME analysis set was evaluated.

Favorable microbiological response=eradication: absence (or urine quantification \<10\^3 CFU/mL for cUTI participants) of causative pathogen from appropriately obtained specimen at site of infection or presumed eradication: repeat culture of specimens were not performed/clinically indicated in participant who had clinical cure (specific to cIAI,HAP/VAP participants). 95% CI was calculated using Jeffrey's method. ME analysis set: participants received 3 days of study intervention,or received study intervention for \>= 48 hours with \>=80% compliance or for \<48 hours before discontinuation due to adverse event, no concomitant antibiotics against baseline carbapenem-resistant gram negative pathogens between first dose and TOC (excluding participants with failed study therapy requiring additional antibiotics), had baseline organisms confirmed by central microbiological testing, no indeterminate clinical outcome at EOT/TOC, no important protocol deviations that affect assessment of efficacy.

Outcome measures

Outcome measures
Measure	Ceftazidime-Avibactam n=14 Participants Participants with confirmed carbapenem-resistant Gram-negative pathogens infection received CAZ-AVI 2.5 g (2 g ceftazidime + 0.5 g avibactam) administered IV as 2-hour infusion q8h for 14 days.	Best Available Treatment n=19 Participants Participants with confirmed carbapenem-resistant Gram-negative pathogens infection received BAT based on investigative site practice and local epidemiology and guideline for 14 days.
Percentage of Participants With Favorable Per-Participant Microbiological Response at TOC Visit - ME Analysis Set	71.4 Percentage of participants Interval 45.5 to 89.5	31.6 Percentage of participants Interval 14.4 to 53.9

SECONDARY outcome

Timeframe: At EOT visit (Up to 24 hours after last infusion on Day 14)

Favorable microbiological response was defined as eradication or presumed eradication. Eradication was defined as absence (or urine quantification \<10\^3 CFU/mL for cUTI participants) of causative pathogen from an appropriately obtained specimen at the site of infection. Presumed eradication was defined as repeat culture of specimens were not performed/clinically indicated in a participant who had a clinical response of cure (specific to cIAI and HAP/VAP participants). 95% CI was calculated using Jeffrey's method.

Outcome measures

Outcome measures
Measure	Ceftazidime-Avibactam n=27 Participants Participants with confirmed carbapenem-resistant Gram-negative pathogens infection received CAZ-AVI 2.5 g (2 g ceftazidime + 0.5 g avibactam) administered IV as 2-hour infusion q8h for 14 days.	Best Available Treatment n=27 Participants Participants with confirmed carbapenem-resistant Gram-negative pathogens infection received BAT based on investigative site practice and local epidemiology and guideline for 14 days.
Percentage of Participants With Favorable Per-Participant Microbiological Response at EOT Visit - mMITT Analysis Set	81.5 Percentage of participants Interval 64.1 to 92.6	33.3 Percentage of participants Interval 17.9 to 52.1

SECONDARY outcome

Timeframe: At EOT visit (Up to 24 hours after last infusion on Day 14)

Population: ME analysis set was evaluated.

Outcome measures

Outcome measures
Measure	Ceftazidime-Avibactam n=14 Participants Participants with confirmed carbapenem-resistant Gram-negative pathogens infection received CAZ-AVI 2.5 g (2 g ceftazidime + 0.5 g avibactam) administered IV as 2-hour infusion q8h for 14 days.	Best Available Treatment n=19 Participants Participants with confirmed carbapenem-resistant Gram-negative pathogens infection received BAT based on investigative site practice and local epidemiology and guideline for 14 days.
Percentage of Participants With Favorable Per-Participant Microbiological Response at EOT Visit - ME Analysis Set	78.6 Percentage of participants Interval 53.1 to 93.6	42.1 Percentage of participants Interval 22.3 to 64.1

SECONDARY outcome

Timeframe: At TOC visit (From Day 21 up to Day 24)

Population: mMITT analysis set: all participants who met minimum disease requirements, received any amount of study therapy, had at least 1 carbapenem-resistant Gram-negative pathogen in an adequate initial/pre-study culture. Participants with inherently resistant pathogens were excluded. All participants reported under 'Overall Number of Participants Analyzed' contributed data to table but may not have evaluable data for every row. 'Number Analyzed' =number of participants evaluable for the specified rows.

Outcome measures

Outcome measures
Measure	Ceftazidime-Avibactam n=27 Participants Participants with confirmed carbapenem-resistant Gram-negative pathogens infection received CAZ-AVI 2.5 g (2 g ceftazidime + 0.5 g avibactam) administered IV as 2-hour infusion q8h for 14 days.	Best Available Treatment n=27 Participants Participants with confirmed carbapenem-resistant Gram-negative pathogens infection received BAT based on investigative site practice and local epidemiology and guideline for 14 days.
Percentage of Participants With Favorable Per-Pathogen Microbiological Response at TOC Visit - mMITT Analysis Set Escherichia Coli	100.0 Percentage of participants Interval 14.7 to 100.0	—
Percentage of Participants With Favorable Per-Pathogen Microbiological Response at TOC Visit - mMITT Analysis Set Enterococcus Faecium	—	0 Percentage of participants Interval 0.0 to 85.3
Percentage of Participants With Favorable Per-Pathogen Microbiological Response at TOC Visit - mMITT Analysis Set Klebsiella Pneumoniae	63.2 Percentage of participants Interval 40.9 to 81.8	30.4 Percentage of participants Interval 14.8 to 50.7
Percentage of Participants With Favorable Per-Pathogen Microbiological Response at TOC Visit - mMITT Analysis Set Pseudomonas Aeruginosa	37.5 Percentage of participants Interval 11.9 to 70.5	0 Percentage of participants Interval 0.0 to 44.5
Percentage of Participants With Favorable Per-Pathogen Microbiological Response at TOC Visit - mMITT Analysis Set Staphylococcus Aureus	0 Percentage of participants Interval 0.0 to 85.3	—
Percentage of Participants With Favorable Per-Pathogen Microbiological Response at TOC Visit - mMITT Analysis Set Staphylococcus Capitis Subspecies	100.0 Percentage of participants Interval 14.7 to 100.0	—

SECONDARY outcome

Timeframe: At EOT visit (Up to 24 hours after last infusion on Day 14)

Outcome measures

Outcome measures
Measure	Ceftazidime-Avibactam n=27 Participants Participants with confirmed carbapenem-resistant Gram-negative pathogens infection received CAZ-AVI 2.5 g (2 g ceftazidime + 0.5 g avibactam) administered IV as 2-hour infusion q8h for 14 days.	Best Available Treatment n=27 Participants Participants with confirmed carbapenem-resistant Gram-negative pathogens infection received BAT based on investigative site practice and local epidemiology and guideline for 14 days.
Percentage of Participants With Favorable Per-Pathogen Microbiological Response at EOT Visit - mMITT Analysis Set Enterococcus Faecium	—	0 Percentage of participants Interval 0.0 to 85.3
Percentage of Participants With Favorable Per-Pathogen Microbiological Response at EOT Visit - mMITT Analysis Set Escherichia Coli	100.0 Percentage of participants Interval 14.7 to 100.0	—
Percentage of Participants With Favorable Per-Pathogen Microbiological Response at EOT Visit - mMITT Analysis Set Klebsiella Pneumoniae	89.5 Percentage of participants Interval 70.3 to 97.7	39.1 Percentage of participants Interval 21.4 to 59.4
Percentage of Participants With Favorable Per-Pathogen Microbiological Response at EOT Visit - mMITT Analysis Set Pseudomonas Aeruginosa	75.0 Percentage of participants Interval 40.8 to 94.4	0 Percentage of participants Interval 0.0 to 44.5
Percentage of Participants With Favorable Per-Pathogen Microbiological Response at EOT Visit - mMITT Analysis Set Staphylococcus Aureus	0 Percentage of participants Interval 0.0 to 85.3	—
Percentage of Participants With Favorable Per-Pathogen Microbiological Response at EOT Visit - mMITT Analysis Set Staphylococcus Capitis Subspecies	100.0 Percentage of participants Interval 14.7 to 100.0	—

SECONDARY outcome

Timeframe: From first dose of study intervention (Day 1) up to Day 28

Population: Intent-to-Treat (ITT) Analysis Set included all participants randomly assigned to study intervention and who took at least one dose of study intervention.

Percentage of participants who died due to any cause up to Day 28 was reported in this outcome measure. The 95% CI was calculated using the Jeffrey's method.

Outcome measures

Outcome measures
Measure	Ceftazidime-Avibactam n=30 Participants Participants with confirmed carbapenem-resistant Gram-negative pathogens infection received CAZ-AVI 2.5 g (2 g ceftazidime + 0.5 g avibactam) administered IV as 2-hour infusion q8h for 14 days.	Best Available Treatment n=29 Participants Participants with confirmed carbapenem-resistant Gram-negative pathogens infection received BAT based on investigative site practice and local epidemiology and guideline for 14 days.
Percentage of Participants Who Died Due to Any Cause Until Day 28	13.3 Percentage of participants Interval 4.7 to 28.7	13.8 Percentage of participants Interval 4.8 to 29.5

SECONDARY outcome

Timeframe: From start of study treatment on Day 1 up to 32 days after the last dose of study intervention (Up to 46 days)

Population: Safety analysis set included all participants who took any study intervention. Participants were analyzed according to the product they actually received.

An adverse event (AE) was any untoward medical occurrence in a study participant temporally associated with the use of study intervention, whether or not considered related to the study intervention. Treatment-emergent adverse event (TEAE) was any AE that started after the study intervention start date and time.

Outcome measures

Outcome measures
Measure	Ceftazidime-Avibactam n=30 Participants Participants with confirmed carbapenem-resistant Gram-negative pathogens infection received CAZ-AVI 2.5 g (2 g ceftazidime + 0.5 g avibactam) administered IV as 2-hour infusion q8h for 14 days.	Best Available Treatment n=29 Participants Participants with confirmed carbapenem-resistant Gram-negative pathogens infection received BAT based on investigative site practice and local epidemiology and guideline for 14 days.
Number of Participants With Treatment-Emergent Adverse Events	24 Participants	26 Participants

SECONDARY outcome

Timeframe: From start of study treatment on Day 1 up to 32 days after the last dose of study intervention (Up to 46 days)

Population: Safety analysis set included all participants who took any study intervention. Participants were analyzed according to the product they actually received.

Number of participants who discontinued the study due to adverse events were reported in this outcome measure. Discontinuations from study due to TEAEs included all participants with an AE record indicating that the AE caused permanent discontinuation from the study. Permanent discontinuations from any study intervention due to TEAEs included participants with an AE record indicating that action taken with study treatment was drug withdrawn but AE did not cause the participant to be discontinued from study.

Outcome measures

Outcome measures
Measure	Ceftazidime-Avibactam n=30 Participants Participants with confirmed carbapenem-resistant Gram-negative pathogens infection received CAZ-AVI 2.5 g (2 g ceftazidime + 0.5 g avibactam) administered IV as 2-hour infusion q8h for 14 days.	Best Available Treatment n=29 Participants Participants with confirmed carbapenem-resistant Gram-negative pathogens infection received BAT based on investigative site practice and local epidemiology and guideline for 14 days.
Number of Participants With Discontinuation Due to Adverse Events Discontinuations from study due to TEAEs	0 Participants	0 Participants
Number of Participants With Discontinuation Due to Adverse Events Permanent discontinuations from any study intervention due to TEAEs	1 Participants	6 Participants

SECONDARY outcome

Timeframe: From first dose of study treatment (Day 1) until TOC (Up to Day 24)

Population: Safety analysis set included all participants who took any study intervention. Participants were analyzed according to the product they actually received. Here, 'Overall Number of Participants Analyzed' signifies participants evaluable for this outcome measure.

Potentially clinically significant hematology parameters included Hemoglobin (gram/deciliter), Hematocrit (%), Erythrocytes (10\^12/Liter \[L\]): value \< 0.8\*lower limit of normal (LLN) and change (Chg) \> 20% decrease, value \> 1.3\*upper limit of normal (ULN) and Chg \> 30% increase. Platelets (10\^9/L): Value \< 0.65\*LLN and Chg \> 50% decrease, Value \> 1.5\*ULN and Chg \> 100% increase. Leukocytes (10\^9/L): Value \< 0.65\*LLN and Chg \> 60% decrease, Value \> 1.6\*ULN and Chg \> 100% increase. Lymphocytes (10\^9/L): Value \< 0.25\*LLN and Chg \> 75% decrease, Value \> 1.5\*ULN and Chg \> 100% increase. Neutrophils (10\^9/L): Value \< 0.65\*LLN and Chg \> 75% decrease, Value \> 1.6\*ULN and Chg \> 100% increase. Basophils (10\^9/L), Eosinophils (10\^9/L), Monocytes (10\^9/L): Value \> 4.0\*ULN and Chg \> 300% increase. Number of participants with potentially clinically significant values for any hematology parameters were reported in this outcome measure.

Outcome measures

Outcome measures
Measure	Ceftazidime-Avibactam n=29 Participants Participants with confirmed carbapenem-resistant Gram-negative pathogens infection received CAZ-AVI 2.5 g (2 g ceftazidime + 0.5 g avibactam) administered IV as 2-hour infusion q8h for 14 days.	Best Available Treatment n=28 Participants Participants with confirmed carbapenem-resistant Gram-negative pathogens infection received BAT based on investigative site practice and local epidemiology and guideline for 14 days.
Number of Participants With Potentially Clinically Significant Post-baseline Hematology Values	7 Participants	13 Participants

SECONDARY outcome

Timeframe: From first dose of study treatment (Day 1) until TOC (Up to Day 24)

Potentially clinically significant criteria included Bilirubin(mg/dL): \>2.0\*ULN and Chg \>150% increase (inc).Aspartate Aminotransferase,Alanine Aminotransferase(Units/Liter\[U/L\]):\>3.0\*ULN and Chg \>200% inc.Alkaline Phosphatase(U/L):\<0.5\*LLN and Chg \>80% decrease (dec),\> 2.0\*ULN and Chg \>100% inc.Protein,Albumin(g/dL):\<0.5\*LLN and Chg \>50% dec,\>1.5\*ULN and Chg \>50% inc.Blood Urea Nitrogen(mg/dL):\<0.2\*LLN and Chg \>100% dec, \>3.0\*ULN and Chg \>200% inc.Creatinine(mg/dL):\>2.0\*ULN and Chg \>100% inc.Sodium(milliequivalent\[mEq\]/L):\<0.85\*LLN and Chg \>10% dec, \>1.1\*ULN and Chg \>10% inc.Potassium,Chloride(mEq/L):\<0.8\*LLN and Chg \>20% dec, \>1.2\*ULN and Chg \>20% inc.Calcium(mg/dL):\<0.7\*LLN and Chg \>30% dec,\> 1.3\*ULN and Chg \>30% inc.Bicarbonate(mEq/L):\<0.7\*LLN and Chg \>40% dec, \>1.3\*ULN and Chg \>40% inc.Glucose(mg/dL):\<0.6\*LLN and Chg \>40% dec, \>3.0\*ULN and Chg \>200% inc.Number of participants with potentially clinically significant values for any clinical chemistry parameters were reported.

Outcome measures

Outcome measures
Measure	Ceftazidime-Avibactam n=30 Participants Participants with confirmed carbapenem-resistant Gram-negative pathogens infection received CAZ-AVI 2.5 g (2 g ceftazidime + 0.5 g avibactam) administered IV as 2-hour infusion q8h for 14 days.	Best Available Treatment n=28 Participants Participants with confirmed carbapenem-resistant Gram-negative pathogens infection received BAT based on investigative site practice and local epidemiology and guideline for 14 days.
Number of Participants With Potentially Clinically Significant Post-baseline Clinical Chemistry Values	4 Participants	7 Participants

Adverse Events

Ceftazidime-Avibactam

Serious events: 7 serious events

Other events: 17 other events

Deaths: 6 deaths

Best Available Treatment

Serious events: 11 serious events

Other events: 18 other events

Deaths: 9 deaths

Serious adverse events

Other adverse events

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 publication 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

Measure	Ceftazidime-Avibactam n=30 participants at risk Participants with confirmed carbapenem-resistant Gram-negative pathogens infection received CAZ-AVI 2.5 g (2 g ceftazidime + 0.5 g avibactam) administered IV as 2-hour infusion q8h for 14 days.	Best Available Treatment n=29 participants at risk Participants with confirmed carbapenem-resistant Gram-negative pathogens infection received BAT based on investigative site practice and local epidemiology and guideline for 14 days.
Cardiac disorders Cardiac arrest	0.00% 0/30 • From start of study intervention on Day 1 up to 32 days after the last dose of study intervention (up to 46 days) Same event may appear as both non-SAE and SAE but what is presented are distinct events. Event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both serious and non-serious event. All-cause mortality was assessed in ITT analysis set and SAEs and non-SAEs were assessed in safety population.	3.4% 1/29 • From start of study intervention on Day 1 up to 32 days after the last dose of study intervention (up to 46 days) Same event may appear as both non-SAE and SAE but what is presented are distinct events. Event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both serious and non-serious event. All-cause mortality was assessed in ITT analysis set and SAEs and non-SAEs were assessed in safety population.
Cardiac disorders Cardiac failure acute	0.00% 0/30 • From start of study intervention on Day 1 up to 32 days after the last dose of study intervention (up to 46 days) Same event may appear as both non-SAE and SAE but what is presented are distinct events. Event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both serious and non-serious event. All-cause mortality was assessed in ITT analysis set and SAEs and non-SAEs were assessed in safety population.	3.4% 1/29 • From start of study intervention on Day 1 up to 32 days after the last dose of study intervention (up to 46 days) Same event may appear as both non-SAE and SAE but what is presented are distinct events. Event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both serious and non-serious event. All-cause mortality was assessed in ITT analysis set and SAEs and non-SAEs were assessed in safety population.
Gastrointestinal disorders Gastrointestinal haemorrhage	3.3% 1/30 • From start of study intervention on Day 1 up to 32 days after the last dose of study intervention (up to 46 days) Same event may appear as both non-SAE and SAE but what is presented are distinct events. Event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both serious and non-serious event. All-cause mortality was assessed in ITT analysis set and SAEs and non-SAEs were assessed in safety population.	3.4% 1/29 • From start of study intervention on Day 1 up to 32 days after the last dose of study intervention (up to 46 days) Same event may appear as both non-SAE and SAE but what is presented are distinct events. Event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both serious and non-serious event. All-cause mortality was assessed in ITT analysis set and SAEs and non-SAEs were assessed in safety population.
Gastrointestinal disorders Large intestinal obstruction	0.00% 0/30 • From start of study intervention on Day 1 up to 32 days after the last dose of study intervention (up to 46 days) Same event may appear as both non-SAE and SAE but what is presented are distinct events. Event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both serious and non-serious event. All-cause mortality was assessed in ITT analysis set and SAEs and non-SAEs were assessed in safety population.	3.4% 1/29 • From start of study intervention on Day 1 up to 32 days after the last dose of study intervention (up to 46 days) Same event may appear as both non-SAE and SAE but what is presented are distinct events. Event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both serious and non-serious event. All-cause mortality was assessed in ITT analysis set and SAEs and non-SAEs were assessed in safety population.
Gastrointestinal disorders Upper gastrointestinal haemorrhage	0.00% 0/30 • From start of study intervention on Day 1 up to 32 days after the last dose of study intervention (up to 46 days) Same event may appear as both non-SAE and SAE but what is presented are distinct events. Event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both serious and non-serious event. All-cause mortality was assessed in ITT analysis set and SAEs and non-SAEs were assessed in safety population.	3.4% 1/29 • From start of study intervention on Day 1 up to 32 days after the last dose of study intervention (up to 46 days) Same event may appear as both non-SAE and SAE but what is presented are distinct events. Event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both serious and non-serious event. All-cause mortality was assessed in ITT analysis set and SAEs and non-SAEs were assessed in safety population.
General disorders Death	0.00% 0/30 • From start of study intervention on Day 1 up to 32 days after the last dose of study intervention (up to 46 days) Same event may appear as both non-SAE and SAE but what is presented are distinct events. Event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both serious and non-serious event. All-cause mortality was assessed in ITT analysis set and SAEs and non-SAEs were assessed in safety population.	3.4% 1/29 • From start of study intervention on Day 1 up to 32 days after the last dose of study intervention (up to 46 days) Same event may appear as both non-SAE and SAE but what is presented are distinct events. Event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both serious and non-serious event. All-cause mortality was assessed in ITT analysis set and SAEs and non-SAEs were assessed in safety population.
General disorders Pyrexia	0.00% 0/30 • From start of study intervention on Day 1 up to 32 days after the last dose of study intervention (up to 46 days) Same event may appear as both non-SAE and SAE but what is presented are distinct events. Event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both serious and non-serious event. All-cause mortality was assessed in ITT analysis set and SAEs and non-SAEs were assessed in safety population.	3.4% 1/29 • From start of study intervention on Day 1 up to 32 days after the last dose of study intervention (up to 46 days) Same event may appear as both non-SAE and SAE but what is presented are distinct events. Event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both serious and non-serious event. All-cause mortality was assessed in ITT analysis set and SAEs and non-SAEs were assessed in safety population.
Hepatobiliary disorders Acute hepatic failure	3.3% 1/30 • From start of study intervention on Day 1 up to 32 days after the last dose of study intervention (up to 46 days) Same event may appear as both non-SAE and SAE but what is presented are distinct events. Event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both serious and non-serious event. All-cause mortality was assessed in ITT analysis set and SAEs and non-SAEs were assessed in safety population.	0.00% 0/29 • From start of study intervention on Day 1 up to 32 days after the last dose of study intervention (up to 46 days) Same event may appear as both non-SAE and SAE but what is presented are distinct events. Event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both serious and non-serious event. All-cause mortality was assessed in ITT analysis set and SAEs and non-SAEs were assessed in safety population.
Infections and infestations Pneumonia	0.00% 0/30 • From start of study intervention on Day 1 up to 32 days after the last dose of study intervention (up to 46 days) Same event may appear as both non-SAE and SAE but what is presented are distinct events. Event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both serious and non-serious event. All-cause mortality was assessed in ITT analysis set and SAEs and non-SAEs were assessed in safety population.	3.4% 1/29 • From start of study intervention on Day 1 up to 32 days after the last dose of study intervention (up to 46 days) Same event may appear as both non-SAE and SAE but what is presented are distinct events. Event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both serious and non-serious event. All-cause mortality was assessed in ITT analysis set and SAEs and non-SAEs were assessed in safety population.
Infections and infestations Sepsis	3.3% 1/30 • From start of study intervention on Day 1 up to 32 days after the last dose of study intervention (up to 46 days) Same event may appear as both non-SAE and SAE but what is presented are distinct events. Event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both serious and non-serious event. All-cause mortality was assessed in ITT analysis set and SAEs and non-SAEs were assessed in safety population.	0.00% 0/29 • From start of study intervention on Day 1 up to 32 days after the last dose of study intervention (up to 46 days) Same event may appear as both non-SAE and SAE but what is presented are distinct events. Event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both serious and non-serious event. All-cause mortality was assessed in ITT analysis set and SAEs and non-SAEs were assessed in safety population.
Infections and infestations Septic shock	3.3% 1/30 • From start of study intervention on Day 1 up to 32 days after the last dose of study intervention (up to 46 days) Same event may appear as both non-SAE and SAE but what is presented are distinct events. Event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both serious and non-serious event. All-cause mortality was assessed in ITT analysis set and SAEs and non-SAEs were assessed in safety population.	6.9% 2/29 • From start of study intervention on Day 1 up to 32 days after the last dose of study intervention (up to 46 days) Same event may appear as both non-SAE and SAE but what is presented are distinct events. Event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both serious and non-serious event. All-cause mortality was assessed in ITT analysis set and SAEs and non-SAEs were assessed in safety population.
Infections and infestations Urinary tract infection bacterial	3.3% 1/30 • From start of study intervention on Day 1 up to 32 days after the last dose of study intervention (up to 46 days) Same event may appear as both non-SAE and SAE but what is presented are distinct events. Event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both serious and non-serious event. All-cause mortality was assessed in ITT analysis set and SAEs and non-SAEs were assessed in safety population.	0.00% 0/29 • From start of study intervention on Day 1 up to 32 days after the last dose of study intervention (up to 46 days) Same event may appear as both non-SAE and SAE but what is presented are distinct events. Event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both serious and non-serious event. All-cause mortality was assessed in ITT analysis set and SAEs and non-SAEs were assessed in safety population.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/30 • From start of study intervention on Day 1 up to 32 days after the last dose of study intervention (up to 46 days) Same event may appear as both non-SAE and SAE but what is presented are distinct events. Event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both serious and non-serious event. All-cause mortality was assessed in ITT analysis set and SAEs and non-SAEs were assessed in safety population.	3.4% 1/29 • From start of study intervention on Day 1 up to 32 days after the last dose of study intervention (up to 46 days) Same event may appear as both non-SAE and SAE but what is presented are distinct events. Event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both serious and non-serious event. All-cause mortality was assessed in ITT analysis set and SAEs and non-SAEs were assessed in safety population.
Respiratory, thoracic and mediastinal disorders Haemothorax	3.3% 1/30 • From start of study intervention on Day 1 up to 32 days after the last dose of study intervention (up to 46 days) Same event may appear as both non-SAE and SAE but what is presented are distinct events. Event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both serious and non-serious event. All-cause mortality was assessed in ITT analysis set and SAEs and non-SAEs were assessed in safety population.	0.00% 0/29 • From start of study intervention on Day 1 up to 32 days after the last dose of study intervention (up to 46 days) Same event may appear as both non-SAE and SAE but what is presented are distinct events. Event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both serious and non-serious event. All-cause mortality was assessed in ITT analysis set and SAEs and non-SAEs were assessed in safety population.
Respiratory, thoracic and mediastinal disorders Respiratory failure	6.7% 2/30 • From start of study intervention on Day 1 up to 32 days after the last dose of study intervention (up to 46 days) Same event may appear as both non-SAE and SAE but what is presented are distinct events. Event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both serious and non-serious event. All-cause mortality was assessed in ITT analysis set and SAEs and non-SAEs were assessed in safety population.	10.3% 3/29 • From start of study intervention on Day 1 up to 32 days after the last dose of study intervention (up to 46 days) Same event may appear as both non-SAE and SAE but what is presented are distinct events. Event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both serious and non-serious event. All-cause mortality was assessed in ITT analysis set and SAEs and non-SAEs were assessed in safety population.
Vascular disorders Circulatory collapse	0.00% 0/30 • From start of study intervention on Day 1 up to 32 days after the last dose of study intervention (up to 46 days) Same event may appear as both non-SAE and SAE but what is presented are distinct events. Event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both serious and non-serious event. All-cause mortality was assessed in ITT analysis set and SAEs and non-SAEs were assessed in safety population.	3.4% 1/29 • From start of study intervention on Day 1 up to 32 days after the last dose of study intervention (up to 46 days) Same event may appear as both non-SAE and SAE but what is presented are distinct events. Event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both serious and non-serious event. All-cause mortality was assessed in ITT analysis set and SAEs and non-SAEs were assessed in safety population.
Vascular disorders Haemorrhage	0.00% 0/30 • From start of study intervention on Day 1 up to 32 days after the last dose of study intervention (up to 46 days) Same event may appear as both non-SAE and SAE but what is presented are distinct events. Event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both serious and non-serious event. All-cause mortality was assessed in ITT analysis set and SAEs and non-SAEs were assessed in safety population.	3.4% 1/29 • From start of study intervention on Day 1 up to 32 days after the last dose of study intervention (up to 46 days) Same event may appear as both non-SAE and SAE but what is presented are distinct events. Event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both serious and non-serious event. All-cause mortality was assessed in ITT analysis set and SAEs and non-SAEs were assessed in safety population.
Vascular disorders Shock	0.00% 0/30 • From start of study intervention on Day 1 up to 32 days after the last dose of study intervention (up to 46 days) Same event may appear as both non-SAE and SAE but what is presented are distinct events. Event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both serious and non-serious event. All-cause mortality was assessed in ITT analysis set and SAEs and non-SAEs were assessed in safety population.	6.9% 2/29 • From start of study intervention on Day 1 up to 32 days after the last dose of study intervention (up to 46 days) Same event may appear as both non-SAE and SAE but what is presented are distinct events. Event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both serious and non-serious event. All-cause mortality was assessed in ITT analysis set and SAEs and non-SAEs were assessed in safety population.