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    Clinical Trial Results:
    A prospective, randomized, open-label, comparative study to assess the efficacy, safety and tolerability of aztreonam-avibactam (ATM-AVI) and best available therapy for the treatment of serious infections due to multi-drug resistant gram-negative bacteria producing metallo-β-lactamase (MBL)

    Summary
    EudraCT number
    		 2017-004544-38
    Trial protocol
    		 GR   RO  
    Global end of trial date
    23 Jan 2023

    Results information
    Results version number
    		 v1(current)
    This version publication date
    28 Jan 2024
    First version publication date
    28 Jan 2024
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    C3601009
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT03580044
    WHO universal trial number (UTN)
    		 -
    Other trial identifiers
    		 Assemble: Other study ID
    Sponsors
    Sponsor organisation name
    Pfizer Inc.
    Sponsor organisation address
    235 E 42nd Street, New York, United States, NY 10017
    Public contact
    Pfizer ClinicalTrials.gov Call Center, Pfizer Inc., 001 8007181021, ClinicalTrials.gov_Inquiries@pfizer.com
    Scientific contact
    Pfizer ClinicalTrials.gov Call Center, Pfizer Inc., 001 8007181021, ClinicalTrials.gov_Inquiries@pfizer.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    30 Jun 2023
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    23 Jan 2023
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    To evaluate the efficacy, of aztreonam- avibactam (ATM- AVI) and best available therapy (BAT) at the Test of Cure (TOC) visit in the microbiological Intent- To-Treat (micro-ITT) population for the treatment of selected serious infections that are due to MBL-producing Gram-negative bacteria.
    Protection of trial subjects
    The study was in compliance with the ethical principles derived from the Declaration of Helsinki and in compliance with all International Council for Harmonization (ICH) Good Clinical Practice (GCP) Guidelines. All the local regulatory requirements pertinent to safety of trials subjects were followed.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    25 Dec 2020
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    China: 2
    Country: Number of subjects enrolled
    Greece: 3
    Country: Number of subjects enrolled
    India: 1
    Country: Number of subjects enrolled
    Malaysia: 2
    Country: Number of subjects enrolled
    Mexico: 1
    Country: Number of subjects enrolled
    Philippines: 1
    Country: Number of subjects enrolled
    Romania: 2
    Country: Number of subjects enrolled
    Russian Federation: 2
    Country: Number of subjects enrolled
    Thailand: 1
    Worldwide total number of subjects
    15
    EEA total number of subjects
    5
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    10
    From 65 to 84 years
    5
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 Subjects hospitalized with a diagnosis of complicated intra-abdominal infection (cIAI), nosocomial pneumonia (NP) including hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP), complicated urinary tract infection (cUTI), or bloodstream infections (BSI) due to producing Gram-negative bacteria were enrolled.

    Pre-assignment
    Screening details
    		 A total of 15 subjects signed the informed consent form and were randomized in the study. This study was conducted across 9 countries from 25 Dec-2020 to 23-Jan-2023. The study was terminated as recruitment of subjects with serious infections caused by gram-negative bacteria producing MBL was challenging.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Aztreonam- Avibactam (ATM- AVI)
    Arm description
    		 Subjects were administered a loading dose of aztreonam- avibactam (ATM-AVI) by intravenous (IV) infusion over 30 minutes immediately followed by an extended loading dose of ATM-AVI by infusion over 3 hours, and then started a maintenance dose of ATM-AVI by IV infusion over 3 hours on Day 1. Subjects with creatinine clearance >50 milliliters per minute (mL/min) and >30 to 50 mL per minute were administered maintenance dose once every 6 hours for maximum of 14 days. Subjects with creatinine clearance >15 to 30 mL/min were administered maintenance dose once every 8 hours for maximum of 14 days. Subjects with cIAI also received metronidazole (MTZ) 500 milligram (mg) every 8 hours by IV infusion over 60 minutes.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Aztreonam
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder for concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Aztreonam 2 gram powder concentrate for infusion.

    Investigational medicinal product name
    Metronidazole
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Metronidazole 500 mg/100 millilitre (mL) solution for infusion.

    Investigational medicinal product name
    Avibactam
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder for concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Avibactam 600 milligrams (mg) powder concentrate for infusion.

    Arm title
    		 Best Available Therapy (BAT)
    Arm description
    		 Subjects who were hospitalized with a diagnosis of cIAI, NP, HAP, VAP, cUTI or BSI received Best Available Therapy (BAT) based upon site practice and local epidemiology for a maximum of 14 days. Subjects with cIAI in the BAT arm received metronidazole if BAT did not provide adequate anaerobic coverage.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    BAT
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Based on investigative site practice and local epidemiology.

    Number of subjects in period 1
    		Aztreonam- Avibactam (ATM- AVI) Best Available Therapy (BAT)
    Started
    12
    3
    Treated
    12
    2
    Completed
    9
    1
    Not completed
    3
    2
         Consent withdrawn by subject
    1
    1
         Death
    2
    1

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Aztreonam- Avibactam (ATM- AVI)
    Reporting group description
    		 Subjects were administered a loading dose of aztreonam- avibactam (ATM-AVI) by intravenous (IV) infusion over 30 minutes immediately followed by an extended loading dose of ATM-AVI by infusion over 3 hours, and then started a maintenance dose of ATM-AVI by IV infusion over 3 hours on Day 1. Subjects with creatinine clearance >50 milliliters per minute (mL/min) and >30 to 50 mL per minute were administered maintenance dose once every 6 hours for maximum of 14 days. Subjects with creatinine clearance >15 to 30 mL/min were administered maintenance dose once every 8 hours for maximum of 14 days. Subjects with cIAI also received metronidazole (MTZ) 500 milligram (mg) every 8 hours by IV infusion over 60 minutes.

    Reporting group title
    Best Available Therapy (BAT)
    Reporting group description
    		 Subjects who were hospitalized with a diagnosis of cIAI, NP, HAP, VAP, cUTI or BSI received Best Available Therapy (BAT) based upon site practice and local epidemiology for a maximum of 14 days. Subjects with cIAI in the BAT arm received metronidazole if BAT did not provide adequate anaerobic coverage.

    Reporting group values
    		 Aztreonam- Avibactam (ATM- AVI) Best Available Therapy (BAT) Total
    Number of subjects
    		 12 3 15
    Age Categorical
    Units: Subjects
        <65 years
    		 8 2 10
        65-74 years
    		 3 1 4
        75-84 years
    		 1 0 1
    Age Continuous
    Units: Years
        arithmetic mean (standard deviation)
    		 56.6 ( 17.14 ) 65.7 ( 6.66 ) -
    Sex: Female, Male
    Units: Subjects
        Female
    		 4 2 6
        Male
    		 8 1 9
    Race
    Units: Subjects
        American Indian or Alaska Native
    		 1 0 1
        Asian
    		 6 1 7
        Native Hawaiian or Other Pacific Islander
    		 0 0 0
        Black or African American
    		 0 0 0
        White
    		 5 2 7
        More than one race
    		 0 0 0
        Unknown or Not Reported
    		 0 0 0
    Ethnicity
    Units: Subjects
        Hispanic or Latino
    		 1 0 1
        Not Hispanic or Latino
    		 11 3 14
        Unknown or Not Reported
    		 0 0 0

    End points

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    End points reporting groups
    Reporting group title
    Aztreonam- Avibactam (ATM- AVI)
    Reporting group description
    		 Subjects were administered a loading dose of aztreonam- avibactam (ATM-AVI) by intravenous (IV) infusion over 30 minutes immediately followed by an extended loading dose of ATM-AVI by infusion over 3 hours, and then started a maintenance dose of ATM-AVI by IV infusion over 3 hours on Day 1. Subjects with creatinine clearance >50 milliliters per minute (mL/min) and >30 to 50 mL per minute were administered maintenance dose once every 6 hours for maximum of 14 days. Subjects with creatinine clearance >15 to 30 mL/min were administered maintenance dose once every 8 hours for maximum of 14 days. Subjects with cIAI also received metronidazole (MTZ) 500 milligram (mg) every 8 hours by IV infusion over 60 minutes.

    Reporting group title
    Best Available Therapy (BAT)
    Reporting group description
    		 Subjects who were hospitalized with a diagnosis of cIAI, NP, HAP, VAP, cUTI or BSI received Best Available Therapy (BAT) based upon site practice and local epidemiology for a maximum of 14 days. Subjects with cIAI in the BAT arm received metronidazole if BAT did not provide adequate anaerobic coverage.

    Primary: Percentage of Subjects With Clinical Cure at the Test of Cure (TOC) Visit -Microbiological Intent to Treat (Micro-ITT) Analysis Set

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    End point title
    		 Percentage of Subjects With Clinical Cure at the Test of Cure (TOC) Visit -Microbiological Intent to Treat (Micro-ITT) Analysis Set [1]
    End point description
    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 subjects, no unplanned drainage or surgical intervention was necessary since the initial procedure. The clinical response assessment was determined by a blinded independent adjudication committee. 95% confidence interval (CI) was calculated using Jeffrey’s method. Micro-ITT analysis set was a subset of the ITT analysis set and included all subjects who had at least 1 MBL-positive Gram-negative baseline pathogen from an adequate specimen at the start of study treatment. 99999 indicates data could not be calculated due to insufficient number of subjects.
    End point type
    Primary
    End point timeframe
    Day 28
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No statistical analysis was planned for this endpoint
    End point values
    		 Aztreonam- Avibactam (ATM- AVI) Best Available Therapy (BAT)
    Number of subjects analysed
    12
    3
    Units: Percentage of subjects
        number (confidence interval 95%)
    41.7 (18.0 to 68.8)
    0.0 (-99999 to 99999)
    No statistical analyses for this end point

    Secondary: Percentage of Subjects With Clinical Cure at the End of Treatment (EOT) Visit- Micro-ITT Analysis Set

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    End point title
    		 Percentage of Subjects With Clinical Cure at the End of Treatment (EOT) Visit- Micro-ITT Analysis Set
    End point description
    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 subjects, no unplanned drainage or surgical intervention was necessary since the initial procedure. The clinical response assessment was determined by a blinded independent adjudication committee. 95% CI was calculated using Jeffrey’s method. Micro-ITT analysis set was a subset of the ITT analysis set and included all subjects who had at least 1 MBL-positive Gram-negative baseline pathogen from an adequate specimen at the start of study treatment. 99999 indicates data could not be calculated due to insufficient number of subjects.
    End point type
    Secondary
    End point timeframe
    Up to 24 hours after the last infusion on Day 14
    End point values
    		 Aztreonam- Avibactam (ATM- AVI) Best Available Therapy (BAT)
    Number of subjects analysed
    12
    3
    Units: Percentage of subjects
        number (confidence interval 95%)
    58.3 (31.2 to 82.0)
    0.0 (-99999 to 99999)
    No statistical analyses for this end point

    Secondary: Percentage of Subjects With Clinical Cure at the TOC Visit-Microbiologically Evaluable (ME) Analysis Set

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    End point title
    		 Percentage of Subjects With Clinical Cure at the TOC Visit-Microbiologically Evaluable (ME) Analysis Set
    End point description
    Clinical cure = 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 subjects, no unplanned drainage or surgical intervention was necessary since the initial procedure. The clinical response assessment was determined by a blinded independent adjudication committee. 95% CI calculated using Jeffrey’s method. ME analysis set: Subjects from micro-ITT who received at least 48 hours of study therapy or <48 hours before discontinuation due to an adverse event, no concomitant antibiotics against baseline MBL positive pathogens between 1st dose and TOC (excluding subjects with failed study therapy requiring additional antibiotics), had baseline organisms confirmed by central microbiological testing (except when locally confirmed) and no indeterminate clinical outcomes at TOC. 99999= data could not be calculated due to insufficient number of subjects.
    End point type
    Secondary
    End point timeframe
    Day 28
    End point values
    		 Aztreonam- Avibactam (ATM- AVI) Best Available Therapy (BAT)
    Number of subjects analysed
    9
    1
    Units: Percentage of subjects
        number (confidence interval 95%)
    55.6 (25.4 to 82.7)
    0.0 (-99999 to 99999)
    No statistical analyses for this end point

    Secondary: Percentage of Subjects With Clinical Cure at the EOT Visit- ME Analysis Set

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    End point title
    		 Percentage of Subjects With Clinical Cure at the EOT Visit- ME Analysis Set
    End point description
    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.For cIAI subjects,no unplanned drainage or surgical intervention was necessary since the initial procedure.The clinical response assessment was determined by a blinded independent adjudication committee.95% CI was calculated using Jeffrey’s method.ME analysis set:Subjects from micro-ITT who received at least 48 hours of study therapy or <48 hours before discontinuation due to an adverse event, no concomitant antibiotics against baseline MBL positive pathogens between first dose of study therapy and TOC(excluding subjects with failed study therapy requiring additional antibiotics)had baseline organisms confirmed by central microbiological testing (except when locally confirmed) and no indeterminate clinical outcomes at TOC.99999=data could not be calculated due to insufficient number of subjects.
    End point type
    Secondary
    End point timeframe
    Up to 24 hours after the last infusion on Day 14
    End point values
    		 Aztreonam- Avibactam (ATM- AVI) Best Available Therapy (BAT)
    Number of subjects analysed
    9
    1
    Units: Percentage of subjects
        number (confidence interval 95%)
    66.7 (34.8 to 89.6)
    0.0 (-99999 to 99999)
    No statistical analyses for this end point

    Secondary: Percentage of Subjects With a Favorable Per Subject Microbiological Response at EOT Visit-Micro-ITT Analysis Set

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    End point title
    		 Percentage of Subjects With a Favorable Per Subject Microbiological Response at EOT Visit-Micro-ITT Analysis Set
    End point description
    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 subjects) 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 subject who had a clinical response of cure (specific to cIAI and HAP/VAP subjects). Micro-ITT analysis set was a subset of the ITT analysis set and included all subjects who had at least 1 MBL-positive Gram-negative baseline pathogen from an adequate specimen at the start of study treatment. Subjects with a per subject response of Indeterminate were excluded from this analysis. Here ‘Number of Subjects Analyzed’ signifies subjects evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    Up to 24 hours after the last infusion on Day 14
    End point values
    		 Aztreonam- Avibactam (ATM- AVI) Best Available Therapy (BAT)
    Number of subjects analysed
    11
    1
    Units: Percentage of subjects
        number (not applicable)
    81.82
    0.0
    No statistical analyses for this end point

    Secondary: Percentage of Subjects With a Favorable Per Subject Microbiological Response at TOC Visit-Micro-ITT Analysis Set

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    End point title
    		 Percentage of Subjects With a Favorable Per Subject Microbiological Response at TOC Visit-Micro-ITT Analysis Set
    End point description
    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 subjects) 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 subject who had a clinical response of cure (specific to cIAI and HAP/VAP subjects). Micro-ITT analysis set was a subset of the ITT analysis set and included all subjects who had at least 1 MBL-positive Gram-negative baseline pathogen from an adequate specimen at the start of study treatment. Subjects with a per subject response of Indeterminate were excluded from this analysis. Here ‘Number of Subjects Analyzed’ signifies participants evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    Day 28
    End point values
    		 Aztreonam- Avibactam (ATM- AVI) Best Available Therapy (BAT)
    Number of subjects analysed
    10
    1
    Units: Percentage of subjects
        number (not applicable)
    60.00
    0.0
    No statistical analyses for this end point

    Secondary: Percentage of Subjects With a Favorable Per Subject Microbiological Response at EOT Visit-ME Analysis Set

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    End point title
    		 Percentage of Subjects With a Favorable Per Subject Microbiological Response at EOT Visit-ME Analysis Set
    End point description
    Favorable microbiological response was defined as eradication or presumed eradication. Eradication was defined as absence (or urine quantification <10^3 CFU/mL for cUTI subjects) 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 subject who had a clinical response of cure (specific to cIAI and HAP/VAP subjects). ME analysis set: Subjects from micro-ITT who received at least 48 hours of study therapy or <48 hours before discontinuation due to an adverse event; no concomitant antibiotics against baseline MBL positive pathogens between first dose of study therapy and TOC (excluding subjects with failed study therapy requiring additional antibiotics), had baseline organisms confirmed by central microbiological testing (except when locally confirmed) and no indeterminate clinical outcomes at TOC.
    End point type
    Secondary
    End point timeframe
    Up to 24 hours after the last infusion on Day 14
    End point values
    		 Aztreonam- Avibactam (ATM- AVI) Best Available Therapy (BAT)
    Number of subjects analysed
    9
    1
    Units: Percentage of subjects
        number (not applicable)
    66.67
    0.00
    No statistical analyses for this end point

    Secondary: Percentage of Subjects With a Favorable Per Subject Microbiological Response at TOC Visit-ME Analysis Set

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    End point title
    		 Percentage of Subjects With a Favorable Per Subject Microbiological Response at TOC Visit-ME Analysis Set
    End point description
    Favorable microbiological response was defined as eradication or presumed eradication. Eradication was defined as absence (or urine quantification <10^3 CFU/mL for cUTI subjects) 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 subject who had a clinical response of cure (specific to cIAI and HAP/VAP subjects). ME analysis set: Subjects from micro-ITT who received at least 48 hours of study therapy or <48 hours before discontinuation due to an adverse event, no concomitant antibiotics against baseline MBL positive pathogens between first dose of study therapy and TOC (excluding subjects with failed study therapy requiring additional antibiotics), had baseline organisms confirmed by central microbiological testing (except when locally confirmed) and no indeterminate clinical outcomes at TOC.
    End point type
    Secondary
    End point timeframe
    Day 28
    End point values
    		 Aztreonam- Avibactam (ATM- AVI) Best Available Therapy (BAT)
    Number of subjects analysed
    9
    1
    Units: Percentage of subjects
        number (not applicable)
    66.7
    0.00
    No statistical analyses for this end point

    Secondary: Percentage of Pathogens According to Favourable Per-Pathogen Microbiological Response at the EOT Visit-Micro-ITT Analysis Set

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    End point title
    		 Percentage of Pathogens According to Favourable Per-Pathogen Microbiological Response at the EOT Visit-Micro-ITT Analysis Set
    End point description
    Favorable microbiological response was defined as eradication or presumed eradication. Eradication: absence (or urine quantification <10^3 CFU/mL for cUTI subjects) 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 subject who had a clinical response of cure (specific to cIAI and HAP/VAP subjects). Micro-ITT analysis set was a subset of the ITT analysis set and included all subjects who had at least 1 MBL-positive Gram-negative baseline pathogen from an adequate specimen at the start of study treatment. Here, n= pathogens evaluable for specified rows. 99999 indicates data could not be calculated due to insufficient pathogen.
    End point type
    Secondary
    End point timeframe
    Up to 24 hours after the last infusion on Day 14
    End point values
    		 Aztreonam- Avibactam (ATM- AVI) Best Available Therapy (BAT)
    Number of subjects analysed
    12
    3
    Units: Percentage of pathogens
    number (not applicable)
        Enterobacterales (n=12,3)
    75.0
    0.0
        Pseudomonas aeruginosa (n=2,0)
    50.0
    99999
        Stenotrophomonas maltophilia (n=3,0)
    66.7
    99999
        Enterococcus faecium (n=1,0)
    100.0
    99999
    No statistical analyses for this end point

    Secondary: Percentage of Pathogens According to Favourable Per-Pathogen Microbiological Response at the TOC Visit-Micro-ITT Analysis Set

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    End point title
    		 Percentage of Pathogens According to Favourable Per-Pathogen Microbiological Response at the TOC Visit-Micro-ITT Analysis Set
    End point description
    Favorable microbiological response was defined as eradication or presumed eradication. Eradication: absence (or urine quantification <10^3 CFU/mL for cUTI subjects) 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 subject who had a clinical response of cure (specific to cIAI and HAP/VAP subject).Micro-ITT analysis set was a subset of the ITT analysis set and included all subjects who had at least 1 MBL-positive Gram-negative baseline pathogen from an adequate specimen at the start of study treatment. n= pathogens evaluable for specified rows. 99999 indicates data could not be calculated due to insufficient pathogen.
    End point type
    Secondary
    End point timeframe
    Day 28
    End point values
    		 Aztreonam- Avibactam (ATM- AVI) Best Available Therapy (BAT)
    Number of subjects analysed
    12
    3
    Units: Percentage of pathogens
    number (not applicable)
        Enterobacterales (n=12,3)
    50.0
    0.00
        Pseudomonas aeruginosa (n=2,0)
    0.0
    99999
        Stenotrophomonas maltophilia (n=3,0)
    33.3
    99999
        Enterococcus faecium (n=1,0)
    0.0
    99999
    No statistical analyses for this end point

    Secondary: Percentage of Pathogens According to Favourable Per-Pathogen Microbiological Response at the EOT Visit-ME Analysis Set

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    End point title
    		 Percentage of Pathogens According to Favourable Per-Pathogen Microbiological Response at the EOT Visit-ME Analysis Set
    End point description
    Favorable microbiological response was defined as eradication or presumed eradication. Eradication: absence (or urine quantification <10^3 CFU/mL for cUTI subjects)of causative pathogen from an appropriately obtained specimen at the site of infection. Presumed eradication: repeat culture of specimens were not performed/clinically indicated in a subject who had a clinical response of cure (specific to cIAI and HAP/VAP subjects). ME analysis set: Subjects from micro-ITT who received at least 48 hours or <48 hours of study therapy before discontinuation due to AE,no concomitant antibiotics against baseline MBL positive pathogens between 1st dose and TOC (excluding those with failed study therapy requiring additional antibiotics),had baseline organisms confirmed by central microbiological testing (except when locally confirmed);no indeterminate clinical outcomes at TOC. n= pathogens evaluable for specified rows. 99999= data could not be calculated due to insufficient pathogens.
    End point type
    Secondary
    End point timeframe
    Up to 24 hours after the last infusion on Day 14
    End point values
    		 Aztreonam- Avibactam (ATM- AVI) Best Available Therapy (BAT)
    Number of subjects analysed
    9
    1
    Units: Percentage of pathogens
    number (not applicable)
        Enterobacterales (n=10,1)
    80.0
    0.0
        Stenotrophomonas maltophilia (n=2,0)
    100.0
    99999
        Enterococcus faecium (n=1,0)
    100.0
    99999
    No statistical analyses for this end point

    Secondary: Percentage of Pathogens According to Favourable Per-Pathogen Microbiological Response at the TOC Visit-ME Analysis Set

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    End point title
    		 Percentage of Pathogens According to Favourable Per-Pathogen Microbiological Response at the TOC Visit-ME Analysis Set
    End point description
    Favorable microbiological response was defined as eradication or presumed eradication. Eradication:absence (or urine quantification <10^3 CFU/mL for cUTI subjects)of causative pathogen from an appropriately obtained specimen at the site of infection. Presumed eradication: repeat culture of specimens were not performed/clinically indicated in a subject who had a clinical response of cure (specific to cIAI and HAP/VAP subjects). ME analysis set: Subjects from micro-ITT who received at least 48 hours or <48 hours of study therapy before discontinuation due to AE,no concomitant antibiotics against baseline MBL positive pathogens between 1st dose and TOC (excluding those with failed study therapy requiring additional antibiotics),had baseline organisms confirmed by central microbiological testing (except when locally confirmed);no indeterminate clinical outcomes at TOC. n= pathogens evaluable for specified rows. 99999= data could not be calculated due to insufficient number of subjects.
    End point type
    Secondary
    End point timeframe
    Day 28
    End point values
    		 Aztreonam- Avibactam (ATM- AVI) Best Available Therapy (BAT)
    Number of subjects analysed
    9
    1
    Units: Percentage of pathogens
    number (not applicable)
        Enterobacterales (n= 10,1)
    60.0
    0.0
        Stenotrophomonas maltophilia (n=2,0)
    50.0
    99999
        Enterococcus faecium (n=1,0)
    0.0
    99999
    No statistical analyses for this end point

    Secondary: Percentage of Subjects who Died Within 28 Days From Randomisation- Micro ITT Analysis Set

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    End point title
    		 Percentage of Subjects who Died Within 28 Days From Randomisation- Micro ITT Analysis Set
    End point description
    Percentage of subjects who died due to any cause on or before 28 days after randomisation were reported in this this endpoint. Micro-ITT analysis set was a subset of the ITT analysis set and included all subjects who had at least 1 MBL-positive Gram-negative baseline pathogen from an adequate specimen at the start of study treatment.
    End point type
    Secondary
    End point timeframe
    From randomisation up to Day 28
    End point values
    		 Aztreonam- Avibactam (ATM- AVI) Best Available Therapy (BAT)
    Number of subjects analysed
    12
    3
    Units: Percentage of subjects
        number (not applicable)
    8.3
    33.3
    No statistical analyses for this end point

    Secondary: Percentage of Subjects who Died Within 28 Days From Randomisation-ITT Analysis Set

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    End point title
    		 Percentage of Subjects who Died Within 28 Days From Randomisation-ITT Analysis Set
    End point description
    Percentage of subjects who died due to any cause on or before 28 days after randomisation were reported in this endpoint. ITT analysis set included all randomized subjects regardless of receipt of study drug.
    End point type
    Secondary
    End point timeframe
    From randomisation up to Day 28
    End point values
    		 Aztreonam- Avibactam (ATM- AVI) Best Available Therapy (BAT)
    Number of subjects analysed
    12
    3
    Units: Percentage of subjects
        number (not applicable)
    8.3
    33.3
    No statistical analyses for this end point

    Secondary: Number of Subjects With Treatment Emergent Adverse Events and Serious Adverse Events

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    End point title
    		 Number of Subjects With Treatment Emergent Adverse Events and Serious Adverse Events
    End point description
    An adverse event (AE) was any untoward medical occurrence in a study subject administered a product or medical device; the event need not necessarily have a causal relationship with the treatment or usage. A serious adverse event (SAE) was any untoward medical occurrence at any dose that: resulted in death; was life-threatening (immediate risk of death); required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/ incapacity; resulted in congenital anomaly/birth defect; considered an important medical event. Treatment-emergent adverse event (TEAE) was any AE that started after the study medication start date and time. Safety analysis set included all subjects who received any amount of study treatment. Subjects were analysed according to the treatment they received.
    End point type
    Secondary
    End point timeframe
    From first dose of study treatment (Day 1) until late follow-up visit (Up to Day 45)
    End point values
    		 Aztreonam- Avibactam (ATM- AVI) Best Available Therapy (BAT)
    Number of subjects analysed
    12
    2
    Units: Subjects
        TEAEs
    11
    2
        SAEs
    5
    2
    No statistical analyses for this end point

    Secondary: Number of Subjects With Vital Sign Abnormalities

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    End point title
    		 Number of Subjects With Vital Sign Abnormalities
    End point description
    Vital signs included blood pressure and heart rate and were measured in a supine position after at least 10 minutes of rest for the subjects. Criteria for vital sign abnormalities included: systolic blood pressure (SBP): value >150 millimeters of mercury (mmHg) and increase from baseline >=30 mmHg and value <90 and decrease from baseline >=30. Diastolic BP (DBP) (mm Hg) Value >100 and increase from baseline >= 20 and Value <50 and decrease from baseline >=20. Heart Rate (beats per minute [BPM]) Value <40 or >120. Safety analysis set included all subjects who received any amount of study treatment. Subjects were analyzed according to the treatment they received. Here ‘Number of Subjects Analysed’ signifies subjects evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    From first dose of study treatment (Day 1) until TOC (Up to Day 28)
    End point values
    		 Aztreonam- Avibactam (ATM- AVI) Best Available Therapy (BAT)
    Number of subjects analysed
    11
    2
    Units: Subjects
        SBP: Value >150 and increase from baseline >=30
    3
    0
        SBP: Value <90 and decrease from baseline >=30
    0
    1
        DBP: Value >100 and increase from baseline >=20
    0
    0
        DBP: Value <50 and decrease from baseline >=20
    0
    0
        Heart Rate (BPM): <40 or >120
    6
    2
    No statistical analyses for this end point

    Secondary: Number of Subjects With Abnormal Physical Examination Findings

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    End point title
    		 Number of Subjects With Abnormal Physical Examination Findings
    End point description
    Physical examination included assessment of the following: abdomen, cardiovascular, ears, eyes, general appearance, head, lungs, lymph nodes, musculoskeletal, neurological, nose, skin and throat. Number of subjects with abnormal physical examination findings for each body system is reported in this outcome measure. Safety analysis set included all subjects who received any amount of study treatment. Subjects were analyzed according to the treatment they received. Here, 'Number Analyzed’= subjects evaluable for specified rows.
    End point type
    Secondary
    End point timeframe
    Baseline (last non-missing value observed before start of treatment on Day 1), EOT (Up to 24 hours after the last infusion on Day 14), TOC (Day 28)
    End point values
    		 Aztreonam- Avibactam (ATM- AVI) Best Available Therapy (BAT)
    Number of subjects analysed
    12
    2
    Units: Subjects
        Abdomen - Baseline (n=12,2)
    3
    0
        Abdomen - End of Treatment (11,1)
    4
    0
        Abdomen -Test of cure (8,1)
    2
    0
        Cardiovascular - Baseline (n=12,2)
    1
    2
        Cardiovascular - End of Treatment (11,1)
    1
    1
        Cardiovascular -Test of cure (8,1)
    0
    1
        Ears- Baseline (n=12,2)
    0
    0
        Ears - End of Treatment (11,1)
    0
    0
        Ears-Test of cure (8,1)
    0
    0
        Eyes - Baseline (n=12,2)
    2
    0
        Eyes - End of Treatment (11,1)
    3
    0
        Eyes -Test of cure (8,1)
    1
    0
        General Appearance- Baseline (n=12,2)
    5
    1
        General Appearance - End of Treatment (11,1)
    3
    0
        General Appearance-Test of cure (8,1)
    0
    0
        Head- Baseline (n=12,2)
    2
    0
        Head- End of Treatment (11,1)
    2
    0
        Head- Test of cure (8,1)
    0
    0
        Lungs- Baseline (n=12,2)
    4
    1
        Lungs-End of Treatment (11,1)
    2
    0
        Lungs-Test of cure (8,1)
    1
    0
        Lymph Nodes-Baseline (n=12,2)
    0
    0
        Lymph Nodes-End of Treatment (11,1)
    0
    0
        Lymph Nodes-Test of cure (8,1)
    0
    0
        Musculoskeletal-Baseline (n=12,2)
    3
    2
        Musculoskeletal-End of Treatment (11,1)
    1
    1
        Musculoskeletal-Test of cure (8,1)
    1
    1
        Neurological-Baseline (n=12,2)
    8
    1
        Neurological-End of Treatment (11,1)
    5
    0
        Neurological-Test of cure (8,1)
    3
    0
        Nose-Baseline (n=12,2)
    1
    0
        Nose-End of Treatment (11,1)
    0
    0
        Nose-Test of cure (8,1)
    0
    0
        Skin-Baseline (n=12,2)
    5
    0
        Skin-End of Treatment (11,1)
    3
    0
        Skin-Test of cure (8,1)
    1
    0
        Throat-Baseline (n=11,2)
    0
    1
        Throat-End of Treatment (11,1)
    1
    0
        Throat-Test of cure (8,1)
    1
    0
    No statistical analyses for this end point

    Secondary: Number of Subjects With Clinically Significant Abnormalities in Hematology Assessments

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    End point title
    		 Number of Subjects With Clinically Significant Abnormalities in Hematology Assessments
    End point description
    Potential clinically significant criteria included: Hematocrit, hemoglobin and erythrocytes <0.7*lower limit of normal (LLN) and >30% Decrease from Baseline (DFB) or >1.3*upper limit of normal (ULN) and >30% Increase from Baseline (IFB); Leukocytes:<0.65*LLN and >60% DFB or >1.5*ULN and >100% DFB; Basophils/Leukocytes, Eosinophils/Leukocytes and Monocytes/Leukocytes:>4.0*ULN and >300% Increase from Baseline; Lymphocytes/Leukocytes <0.25*LLN and >75% DFB and >1.5* ULN and >100% IFB; Neutrophils/Leukocytes: <0.65*LLN and >75% DFB or >1.6*ULN and >100% IFB; Platelets<0.65*LLN and >50% DFB or >1.5*ULN and >100% IFB. Safety analysis set- all subjects who received any amount of study treatment. Subjects were analyzed according to the treatment received. All subjects reported under ‘N’ contributed data to the table but may not have evaluable data for every row. ‘n’= subjects evaluable for specified rows.
    End point type
    Secondary
    End point timeframe
    From first dose of study treatment (Day 1) until TOC (Up to Day 28)
    End point values
    		 Aztreonam- Avibactam (ATM- AVI) Best Available Therapy (BAT)
    Number of subjects analysed
    12
    2
    Units: Subjects
        Hematocrit: <0.7*LLN & >30% DFB (n=11,1)
    0
    0
        Hematocrit: >1.3*ULN & >30% IFB (n=11,1)
    0
    0
        Hemoglobin: <0.7*LLN & >30% DFB (n=11,1)
    0
    0
        Hemoglobin: >1.3*ULN & >30% IFB (n=11,1)
    0
    0
        Erythrocytes: <0.7*LLN & >30% DFB (n=11,1)
    0
    0
        Erythrocytes: >1.3*ULN & >30% IFB (n=11,1)
    0
    0
        Leukocytes: <0.65*LLN & >60% DFB (n=11,1)
    0
    0
        Leukocytes:>1.5*ULN & >100% IFB (n=11,1)
    0
    0
        Basophils/Leukocytes: >4.0*ULN & >300% IFB(n=11,1)
    0
    0
        Eosinophils/Leukocytes:>4.0*ULN& >300% IFB(n=11,1)
    0
    0
        Lymphocytes/Leukocytes: <0.25*LLN& >75%DFB(n=11,1)
    0
    0
        Lymphocytes/Leukocytes: >1.5*ULN&>100% IFB(n=11,1)
    0
    0
        Monocytes/Leukocytes:>4.0*ULN & >300% IFB (n=11,1)
    0
    0
        Neutrophils/Leukocytes:<0.65*LLN& >75% DFB(n=11,1)
    0
    0
        Neutrophils/Leukocytes: >1.6*ULN&>100% IFB(n=11,1)
    0
    0
        Platelets: <0.65*LLN & >50% DFB (n=11,1)
    0
    0
        Platelets: >1.5 *ULN & >100% IFB (n=11,1)
    1
    0
    No statistical analyses for this end point

    Secondary: Number of Subjects With Clinically Significant Abnormalities in Clinical Chemistry Assessments

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    End point title
    		 Number of Subjects With Clinically Significant Abnormalities in Clinical Chemistry Assessments
    End point description
    Potential clinically significant criteria included: Aspartate Aminotransferase(AST) and Alanine Aminotransferase (ALT): >3.0*ULN and >100% IFB; Bilirubin: >1.5*ULN and >100% IFB;Direct Bilirubin: >2.0*ULN and >150% IFB; Alkaline Phosphatase (ALP): 80% decrease from baseline (DFB) and >3.0*ULN and >100% IFB; Urea Nitrogen:100% DFB and >3.0*ULN and >200% IFB; Creatinine >2.0*ULN and >100% IFB; Sodium :10% DFB or >1.1*ULN and >10% IFB; Potassium: 20% DFB or >1.2*ULN and >20% IFB; Chloride: 20% DFB or >1.2*ULN and >20% IFB; Bicarbonate: 40% DFB or >1.3*ULN and >40% IFB; Calcium: 30% DFB or >1.3*ULN and >30% IFB; Albumin: 50% DFB or >1.5* ULN and >50% IFB; Glucose: 40% DFB or >3.0*ULN and >200% IFB. Safety analysis set- all subjects who received any amount of study treatment. Subject were analysed according to the treatment received. All subjects reported under ‘N’ contributed data to the table but may not have evaluable data for every row. Here,‘n’= subjects evaluable for specified rows.
    End point type
    Secondary
    End point timeframe
    From first dose of study treatment (Day 1) until TOC (Up to Day 28)
    End point values
    		 Aztreonam- Avibactam (ATM- AVI) Best Available Therapy (BAT)
    Number of subjects analysed
    12
    2
    Units: Subjects
        AST: >3.0* ULN & >100% IFB (n=11,1)
    1
    0
        ALT: >3.0* ULN & >100% IFB (n=11,1)
    0
    0
        Bilirubin: >1.5* ULN & >100% IFB (n=11,1)
    1
    0
        Direct Bilirubin: >2.0* ULN & >150% IFB (n=11,1)
    1
    0
        ALP:80% DFB (n=11,1)
    0
    0
        ALP:>3.0*ULN & >100% IFB (n=11,1)
    1
    0
        Urea Nitrogen:100% DFB (n=11,1)
    0
    0
        Urea Nitrogen:>3.0* ULN & >200% IFB (n=11,1)
    0
    0
        Creatinine:>2.0* ULN & >100% IFB (n=11,2)
    0
    0
        Sodium:10% DFB (n=11,1)
    0
    0
        Sodium:>1.1* ULN & >10% IFB (n=11,1)
    0
    0
        Potassium:20% DFB (n=11,1)
    1
    0
        Potassium:>1.2* ULN & >20% IFB (n=11,1)
    0
    0
        Chloride:20% DFB (n=11,1)
    0
    0
        Chloride:>1.2*ULN & >20% IFB (n=11,1)
    0
    0
        Bicarbonate:40% DFB (n=11,1)
    0
    0
        Bicarbonate:>1.3* ULN & >40% IFB (n=11,1)
    0
    0
        Calcium:30% DFB (n=11,1)
    0
    0
        Calcium:>1.3* ULN & >30% IFB (n=11,1)
    0
    0
        Albumin:50% DFB (n=11,1)
    0
    0
        Albumin:>1.5* ULN & >50% IFB (n=11,1)
    0
    0
        Glucose:40% DFB (n=11,1)
    0
    0
        Glucose:>3.0*ULN & >200% IFB (n=11,1)
    0
    0
    No statistical analyses for this end point

    Secondary: Number of Subjects With Clinically Significant Abnormalities in Electrocardiogram (ECG)

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    End point title
    		 Number of Subjects With Clinically Significant Abnormalities in Electrocardiogram (ECG)
    End point description
    A standard 12-lead ECG was recorded with the subject in a supine position after at least 10 minutes of rest. The following ECG parameters were recorded: heart rate, PR-interval, QRS-duration, QT-interval, QTc-interval, RR interval. Clinical significance of ECG abnormalities were judged by Investigator. Safety analysis set included all subjects who received any amount of study treatment. Subjects were analyzed according to the treatment they received.
    End point type
    Secondary
    End point timeframe
    From first dose of study treatment (Day 1) until TOC (Up to Day 28)
    End point values
    		 Aztreonam- Avibactam (ATM- AVI) Best Available Therapy (BAT)
    Number of subjects analysed
    12
    2
    Units: Subjects
    1
    0
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    From first dose of study drug up to the Last follow up visit (up to maximum of 45 days)
    Adverse event reporting additional description
    Same event may appear as non-SAE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 subject and as non-serious in another subject or 1 subject may have experienced both serious and non-serious event during study. Analysis was performed on safety population.
    Assessment type
    		 Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    25.1
    Reporting groups
    Reporting group title
    Best Available Therapy (BAT)
    Reporting group description
    		 Subjects who were hospitalized with a diagnosis of cIAI, NP, HAP, VAP, cUTI or BSI received Best Available Therapy (BAT) based upon site practice and local epidemiology for a maximum of 14 days. Subjects with cIAI in the BAT arm received metronidazole if BAT did not provide adequate anaerobic coverage.

    Reporting group title
    Aztreonam- Avibactam (ATM- AVI)
    Reporting group description
    		 Subjects were administered a loading dose of aztreonam- avibactam (ATM-AVI) by intravenous (IV) infusion over 30 minutes immediately followed by an extended loading dose of ATM-AVI by infusion over 3 hours, and then started a maintenance dose of ATM-AVI by IV infusion over 3 hours on Day 1. Subjects with creatinine clearance >50 milliliters per minute (mL/min) and >30 to 50 mL per minute were administered maintenance dose once every 6 hours for maximum of 14 days. Subjects with creatinine clearance >15 to 30 mL/min were administered maintenance dose once every 8 hours for maximum of 14 days. Subjects with cIAI also received metronidazole (MTZ) 500 milligram (mg) every 8 hours by IV infusion over 60 minutes.

    Serious adverse events
    		 Best Available Therapy (BAT) Aztreonam- Avibactam (ATM- AVI)
    Total subjects affected by serious adverse events
         subjects affected / exposed
    2 / 2 (100.00%)
    5 / 12 (41.67%)
         number of deaths (all causes)
    1
    2
         number of deaths resulting from adverse events
    1
    2
    Investigations
    Bacterial test positive
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 12 (8.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Enterococcus test positive
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 12 (8.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Neoplasm progression
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 12 (8.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Vascular disorders
    Thrombophlebitis
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 12 (8.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Cardiac arrest
         subjects affected / exposed
    1 / 2 (50.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    General disorders and administration site conditions
    Multiple organ dysfunction syndrome
         subjects affected / exposed
    1 / 2 (50.00%)
    1 / 12 (8.33%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    Respiratory, thoracic and mediastinal disorders
    Acute pulmonary oedema
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 12 (8.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    Urinary tract obstruction
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 12 (8.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acute kidney injury
         subjects affected / exposed
    1 / 2 (50.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Sepsis
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 12 (8.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Pyelonephritis
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 12 (8.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    1 / 2 (50.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    		 Best Available Therapy (BAT) Aztreonam- Avibactam (ATM- AVI)
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    1 / 2 (50.00%)
    9 / 12 (75.00%)
    Vascular disorders
    Phlebitis
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    Haematoma
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    General disorders and administration site conditions
    Chest discomfort
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    Pyrexia
         subjects affected / exposed
    1 / 2 (50.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    Psychiatric disorders
    Intensive care unit delirium
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    Product issues
    Device occlusion
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    Investigations
    Aspartate aminotransferase increased
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    Alanine aminotransferase increased
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    Blood alkaline phosphatase increased
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    Catheter culture positive
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    Blood creatinine increased
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    Platelet count increased
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    Staphylococcus test positive
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    Injury, poisoning and procedural complications
    Stoma prolapse
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    Abdominal wound dehiscence
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    Blood and lymphatic system disorders
    Thrombocytopenia
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    Eye disorders
    Ocular hypertension
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    Gastrointestinal disorders
    Frequent bowel movements
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    Hepatobiliary disorders
    Hepatic function abnormal
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    Skin and subcutaneous tissue disorders
    Decubitus ulcer
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    Skin maceration
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    Renal and urinary disorders
    Ureterolithiasis
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    Infections and infestations
    Bacteraemia
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    Intervertebral discitis
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    Metabolism and nutrition disorders
    Hypokalaemia
         subjects affected / exposed
    0 / 2 (0.00%)
    2 / 12 (16.67%)
         occurrences all number
    0
    3

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    23 May 2022
    Amendment 2.0: Updated section 4: Study eligibility criteria to better reflect the target patient population in clinical practice.

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    Total number of deaths is reported for safety set under Adverse Events section. Actual number of deaths were 2 for Aztreonam-Avibactam and 1 for Best Available Therapy for ITT population as well.
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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