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Ceftazidime-Avibactam for the Treatment of Infections Due to Ceftazidime Resistant Pathogens

Primary Purpose

Complicated Urinary Tract Infection, Complicated Intra-abdominal Infection

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Ceftazidime - Avibactam ( CAZ-AVI)
Best Available Therapy
Metronidazole
Sponsored by
Pfizer
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Complicated Urinary Tract Infection focused on measuring Ceftazidime,, avibactam,, metronidazone,, Anti-Infectives

Eligibility Criteria

18 Years - 90 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Patient must be ≥18 and ≤90 years of age
  • Female patients can participate if they are surgically sterile or completed menopause or females capable of having children and agree not to attempt pregnancy while receiving IV study therapy and for a period of 7 days after
  • Patient has a ceftazidime-resistant Gram negative pathogen that was isolated from an appropriate culture within 5 days prior to study entry (ie, within 5 days prior to Screening; the study-qualifying culture), which was determined to be the causative agent of the entry infection

Exclusion Criteria:

  • Patient has an APACHE II score >30 (cIAI patients only)
  • Patient has an infection due to Gram negative pathogen that is unlikely to respond to CAZ-AVI treatment (eg, Acinetobacter spp., Stenotrophomonas spp.)
  • Patient is receiving hemodialysis or peritoneal dialysis or had a renal transplant Patient is immunocompromised
  • Patient has a rapidly progressive or terminal illness with a high risk of mortality due to any cause, including acute hepatic failure, respiratory failure or severe septic shock such that they are unlikely to survive the 4- to 5-week study period.

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Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Ceftazidime - Avibactam ( CAZ-AVI)

Best Available Therapy

Arm Description

IV treatment

IV treatment

Outcomes

Primary Outcome Measures

Clinical Response at Test of Cure (TOC) in Microbiological Modified Intent-to-treat (mMITT) Analysis Set
Proportion of patients with clinical cure at the TOC visit in the mMITT analysis set. Clinical cure: Complete resolution or significant improvement of signs and symptoms of the index infection such that no further antibacterial therapy (other than those allowed per protocol) is necessary; for cIAI patients no drainage or surgical intervention after 96 hours from randomization is necessary (ie. drainage or surgical intervention up to 96 hours from randomization is permissible).

Secondary Outcome Measures

Clinical Response at End of Treatment (EOT) in mMITT Analysis Set.
Proportion of patients with clinical cure at the EOT visit in the mMITT analysis set. Clinical cure: Complete resolution or significant improvement of signs and symptoms of the index infection such that no further antibacterial therapy (other than those allowed per protocol) is necessary; for cIAI patients no drainage or surgical intervention after 96 hours from randomization is necessary (ie. drainage or surgical intervention up to 96 hours from randomization is permissible).
Clinical Response at Follow-up 1 (FU1) in mMITT Analysis Set
Proportion of patients with clinical cure at the FU1 visit in the mMITT analysis set. Clinical cure: Complete resolution or significant improvement of signs and symptoms of the index infection such that no further antibacterial therapy (other than those allowed per protocol) is necessary; for cIAI patients no drainage or surgical intervention after 96 hours from randomization is necessary (ie. drainage or surgical intervention up to 96 hours from randomization is permissible).
Clinical Response at Follow-up 2 (FU2) in mMITT Analysis Set
Proportion of patients with clinical cure at the FU2 visit in the mMITT analysis set. Clinical cure: Complete resolution or significant improvement of signs and symptoms of the index infection such that no further antibacterial therapy (other than those allowed per protocol) is necessary; for cIAI patients no drainage or surgical intervention after 96 hours from randomization is necessary (ie. drainage or surgical intervention up to 96 hours from randomization is permissible).
Clinical Response at EOT in Extended Microbiologically Evaluable (EME) at EOT Analysis Set.
Proportion of patients with clinical cure at the EOT visit in the EME at EOT analysis set. Clinical cure: Complete resolution or significant improvement of signs and symptoms of the index infection such that no further antibacterial therapy (other than those allowed per protocol) is necessary; for cIAI patients no drainage or surgical intervention after 96 hours from randomization is necessary (ie. drainage or surgical intervention up to 96 hours from randomization is permissible).
Clinical Response at TOC in EME at TOC Analysis Set.
Proportion of patients with clinical cure at the TOC visit in the EME at TOC analysis set. Clinical cure: Complete resolution or significant improvement of signs and symptoms of the index infection such that no further antibacterial therapy (other than those allowed per protocol) is necessary; for cIAI patients no drainage or surgical intervention after 96 hours from randomization is necessary (ie. drainage or surgical intervention up to 96 hours from randomization is permissible).
Clinical Response at FU1 in EME at FU1 Analysis Set.
Proportion of patients with clinical cure at the FU1 visit in EME at FU1 analysis set. Clinical cure: Complete resolution or significant improvement of signs and symptoms of the index infection such that no further antibacterial therapy (other than those allowed per protocol) is necessary; for cIAI patients no drainage or surgical intervention after 96 hours from randomization is necessary (ie. drainage or surgical intervention up to 96 hours from randomization is permissible).
Clinical Response at FU2 in EME at FU2 Analysis Set
Proportion of patients with clinical cure at the FU2 visit in EME at FU2 analysis set. Clinical cure: Complete resolution or significant improvement of signs and symptoms of the index infection such that no further antibacterial therapy (other than those allowed per protocol) is necessary.
Clinical Cure at TOC by Baseline Gram-negative Pathogen in mMITT Analysis Set
Proportion of patients with clinical cure at TOC visit by baseline pathogen (>=10% of frequency in the combined cIAI and cUTI patients) in the mMITT analysis set. Clinical cure: Complete resolution or significant improvement of signs and symptoms of the index infection such that no further antibacterial therapy (other than those allowed per protocol) is necessary; for cIAI patients no drainage or surgical intervention after 96 hours from randomization is necessary (ie. drainage or surgical intervention up to 96 hours from randomization is permissible).
Clinical Cure at TOC by Baseline Gram-negative Pathogen in EME at TOC Analysis Set
Proportion of patients with clinical cure at TOC visit by baseline Gram-negative pathogen (>=10% of frequency in the combined cIAI and cUTI patients) in EME at TOC analysis set. Clinical cure: Complete resolution or significant improvement of signs and symptoms of the index infection such that no further antibacterial therapy (other than those allowed per protocol) is necessary; for cIAI patients no drainage or surgical intervention after 96 hours from randomization is necessary (ie. drainage or surgical intervention up to 96 hours from randomization is permissible).
Clinical Cure at TOC by Previously Failed Treatment Class in mMITT Analysis Set
Proportion of patients with clinical cure at TOC visit by previously failed treatment class in the mMITT analysis set. Clinical cure: Complete resolution or significant improvement of signs and symptoms of the index infection such that no further antibacterial therapy (other than those allowed per protocol) is necessary; for cIAI patients no drainage or surgical intervention after 96 hours from randomization is necessary (ie. drainage or surgical intervention up to 96 hours from randomization is permissible).
Clinical Cure at EOT by Previously Failed Treatment Class in EME at EOT Analysis Set
Proportion of patients with clinical cure at EOT visit by previously failed treatment class in EME at EOT analysis set. Clinical cure: Complete resolution or significant improvement of signs and symptoms of the index infection such that no further antibacterial therapy (other than those allowed per protocol) is necessary; for cIAI patients no drainage or surgical intervention after 96 hours from randomization is necessary (ie. drainage or surgical intervention up to 96 hours from randomization is permissible).
Clinical Cure at TOC by Previously Failed Treatment Class in EME at TOC Analysis Set
Proportion of patients with clinical cure at TOC visit by previously failed treatment class in EME at TOC analysis set. Clinical cure: Complete resolution or significant improvement of signs and symptoms of the index infection such that no further antibacterial therapy (other than those allowed per protocol) is necessary; for cIAI patients no drainage or surgical intervention after 96 hours from randomization is necessary (ie. drainage or surgical intervention up to 96 hours from randomization is permissible).
Clinical Cure at FU1 by Previously Failed Treatment Class in EME at FU1 Analysis Set
Proportion of patients with clinical cure at FU1 visit by previously failed treatment class in EME at FU1 analysis set. Clinical cure: Complete resolution or significant improvement of signs and symptoms of the index infection such that no further antibacterial therapy (other than those allowed per protocol) is necessary; for cIAI patients no drainage or surgical intervention after 96 hours from randomization is necessary (ie. drainage or surgical intervention up to 96 hours from randomization is permissible).
Clinical Cure at FU2 by Previously Failed Treatment Class in EME at FU2 Analysis Set
Proportion of patients with clinical cure at FU2 visit by previously failed treatment class in EME at FU2 analysis set. Clinical cure: Complete resolution or significant improvement of signs and symptoms of the index infection such that no further antibacterial therapy (other than those allowed per protocol) is necessary.
Per-patient Microbiological Response at EOT in mMITT Analysis Set
Microbiological responses as per the protocoled criteria: responses other than "indeterminate" were classified as "favorable" or "unfavorable." Favorable microbiological response assessments included "eradication" and "presumed eradication." Unfavorable microbiological response assessments included "persistence," "persistence with increasing minimum inhibitory concentration (MIC)," and "presumed persistence." Indeterminate microbiologic response assessments included cIAI patients where the clinical response was changed to indeterminate due to a Surgical Review Panel assessment of inadequate source control (ie, circumstances that preclude classification as eradication, presumed eradication, persistence, persistence with increasing MIC, and presumed persistence).
Per-patient Microbiological Response at TOC in mMITT Analysis Set
Microbiological responses as per the protocoled criteria: responses other than "indeterminate" were classified as "favorable" or "unfavorable." Favorable microbiological response assessments included "eradication" and "presumed eradication." Unfavorable microbiological response assessments included "persistence," "persistence with increasing minimum inhibitory concentration (MIC)," and "presumed persistence." Indeterminate microbiologic response assessments included cIAI patients where the clinical response was changed to indeterminate due to a Surgical Review Panel assessment of inadequate source control (ie, circumstances that preclude classification as eradication, presumed eradication, persistence, persistence with increasing MIC, and presumed persistence).
Per-patient Microbiological Response at FU1 in mMITT Analysis Set
Microbiological responses as per the protocoled criteria: responses other than "indeterminate" were classified as "favorable" or "unfavorable." Favorable microbiological response assessments included "eradication" and "presumed eradication." Unfavorable microbiological response assessments included "persistence," "persistence with increasing minimum inhibitory concentration (MIC)," and "presumed persistence." Indeterminate microbiologic response assessments included cIAI patients where the clinical response was changed to indeterminate due to a Surgical Review Panel assessment of inadequate source control (ie, circumstances that preclude classification as eradication, presumed eradication, persistence, persistence with increasing MIC, and presumed persistence).
Per-patient Microbiological Response at FU2 in mMITT Analysis Set
Microbiological responses as per the protocoled criteria: responses other than "indeterminate" were classified as "favorable" or "unfavorable." Favorable microbiological response assessments included "eradication" and "presumed eradication." Unfavorable microbiological response assessments included "persistence," "persistence with increasing minimum inhibitory concentration (MIC)," and "presumed persistence." Indeterminate microbiologic response assessments included cIAI patients where the clinical response was changed to indeterminate due to a Surgical Review Panel assessment of inadequate source control (ie, circumstances that preclude classification as eradication, presumed eradication, persistence, persistence with increasing MIC, and presumed persistence).
Per-patient Microbiological Response at EOT in EME at EOT Analysis Set
Microbiological responses as per the protocoled criteria: responses other than "indeterminate" were classified as "favorable" or "unfavorable." Favorable microbiological response assessments included "eradication" and "presumed eradication." Unfavorable microbiological response assessments included "persistence," "persistence with increasing minimum inhibitory concentration (MIC)," and "presumed persistence." Indeterminate microbiologic response assessments included cIAI patients where the clinical response was changed to indeterminate due to a Surgical Review Panel assessment of inadequate source control (ie, circumstances that preclude classification as eradication, presumed eradication, persistence, persistence with increasing MIC, and presumed persistence).
Per-patient Microbiological Response at TOC in EME at TOC Analysis Set
Microbiological responses as per the protocoled criteria: responses other than "indeterminate" were classified as "favorable" or "unfavorable." Favorable microbiological response assessments included "eradication" and "presumed eradication." Unfavorable microbiological response assessments included "persistence," "persistence with increasing minimum inhibitory concentration (MIC)," and "presumed persistence." Indeterminate microbiologic response assessments included cIAI patients where the clinical response was changed to indeterminate due to a Surgical Review Panel assessment of inadequate source control (ie, circumstances that preclude classification as eradication, presumed eradication, persistence, persistence with increasing MIC, and presumed persistence).
Per-patient Microbiological Response at FU1 in EME at FU1 Analysis Set
Microbiological responses as per the protocoled criteria: responses other than "indeterminate" were classified as "favorable" or "unfavorable." Favorable microbiological response assessments included "eradication" and "presumed eradication." Unfavorable microbiological response assessments included "persistence," "persistence with increasing minimum inhibitory concentration (MIC)," and "presumed persistence." Indeterminate microbiologic response assessments included cIAI patients where the clinical response was changed to indeterminate due to a Surgical Review Panel assessment of inadequate source control (ie, circumstances that preclude classification as eradication, presumed eradication, persistence, persistence with increasing MIC, and presumed persistence).
Per-patient Microbiological Response at FU2 in EME at FU2 Analysis Set
Microbiological responses as per the protocoled criteria: responses other than "indeterminate" were classified as "favorable" or "unfavorable." Favorable microbiological response assessments included "eradication" and "presumed eradication." Unfavorable microbiological response assessments included "persistence," "persistence with increasing minimum inhibitory concentration (MIC)," and "presumed persistence." Indeterminate microbiologic response assessments included cIAI patients where the clinical response was changed to indeterminate due to a Surgical Review Panel assessment of inadequate source control (ie, circumstances that preclude classification as eradication, presumed eradication, persistence, persistence with increasing MIC, and presumed persistence).
Per-pathogen Microbiological Response of Gram-negative Pathogen at EOT in mMITT Analysis Set
Proportion of patients with a favorable per-pathogen microbiological response for pathogens (>=10% of frequency in the combined cIAI and cUTI patients): favourable microbiological response includes: Eradication Absence (or urine quantification less than 10^4 CFU/ml for cUTI patients) of causative pathogen from an appropriately obtained specimen at the site of infection. If the patient was bacteremic at Screening, the bacteremia has also resolved. Presumed eradication where, repeat cultures were not performed/clinically indicated in a patient who had a clinical response of cure (specific to cIAI population).
Per-pathogen Microbiological Response of Gram-negative Pathogen at TOC in mMITT Analysis Set
Proportion of patients with a favorable per-pathogen microbiological response for pathogens (>=10% of frequency in the combined cIAI and cUTI patients): favourable microbiological response includes: Eradication Absence (or urine quantification less than 10^4 CFU/ml for cUTI patients) of causative pathogen from an appropriately obtained specimen at the site of infection. If the patient was bacteremic at Screening, the bacteremia has also resolved. Presumed eradication where, repeat cultures were not performed/clinically indicated in a patient who had a clinical response of cure (specific to cIAI population).
Per-pathogen Microbiological Response of Gram-negative Pathogen at FU1 in mMITT Analysis Set
Proportion of patients with a favorable per-pathogen microbiological response for pathogens (>=10% of frequency in the combined cIAI and cUTI patients): favourable microbiological response includes: Eradication Absence (or urine quantification less than 10^4 CFU/ml for cUTI patients) of causative pathogen from an appropriately obtained specimen at the site of infection. If the patient was bacteremic at Screening, the bacteremia has also resolved. Presumed eradication where, repeat cultures were not performed/clinically indicated in a patient who had a clinical response of cure (specific to cIAI population).
Per-pathogen Microbiological Response of Gram-negative Pathogen at FU2 in mMITT Analysis Set
Proportion of patients with a favorable per-pathogen microbiological response for pathogens (>=10% of frequncy in the combined cIAI and cUTI patients): favourable microbiological response includes: Eradication Absence (or urine quantification less than 10^4 CFU/ml for cUTI patients) of causative pathogen from an appropriately obtained specimen at the site of infection. If the patient was bacteremic at Screening, the bacteremia has also resolved. Presumed eradication where, repeat cultures were not performed/clinically indicated in a patient who had a clinical response of cure (specific to cIAI population).
Per-pathogen Microbiological Response of Gram-negative Pathogen at EOT in EME at EOT Analysis Set
Proportion of patients with a favorable per-pathogen microbiological response for pathogens (>=10% of frequncy in the combined cIAI and cUTI patients): favourable microbiological response includes: Eradication Absence (or urine quantification less than 10^4 CFU/ml for cUTI patients) of causative pathogen from an appropriately obtained specimen at the site of infection. If the patient was bacteremic at Screening, the bacteremia has also resolved. Presumed eradication where, repeat cultures were not performed/clinically indicated in a patient who had a clinical response of cure (specific to cIAI population).
Per-pathogen Microbiological Response of Gram-negative Pathogen at TOC in EME at TOC Analysis Set
Proportion of patients with a favorable per-pathogen microbiological response for pathogens (>=10% of frequncy in the combined cIAI and cUTI patients): favourable microbiological response includes: Eradication Absence (or urine quantification less than 10^4 CFU/ml for cUTI patients) of causative pathogen from an appropriately obtained specimen at the site of infection. If the patient was bacteremic at Screening, the bacteremia has also resolved. Presumed eradication where, repeat cultures were not performed/clinically indicated in a patient who had a clinical response of cure (specific to cIAI population).
Per-pathogen Microbiological Response of Gram-negative Pathogen at FU1 in EME at FU1 Analysis Set
Proportion of patients with a favorable per-pathogen microbiological response for pathogens (>=10% of frequncy in the combined cIAI and cUTI patients): favourable microbiological response includes: Eradication Absence (or urine quantification less than 10^4 CFU/ml for cUTI patients) of causative pathogen from an appropriately obtained specimen at the site of infection. If the patient was bacteremic at Screening, the bacteremia has also resolved. Presumed eradication where, repeat cultures were not performed/clinically indicated in a patient who had a clinical response of cure (specific to cIAI population).
Per-pathogen Microbiological Response of Gram-negative Pathogen at FU2 in EME at FU2 Analysis Set
Proportion of patients with a favorable per-pathogen microbiological response for pathogens (>=10% of frequncy in the combined cIAI and cUTI patients): favourable microbiological response includes: Eradication Absence (or urine quantification less than 10^4 CFU/ml for cUTI patients) of causative pathogen from an appropriately obtained specimen at the site of infection. If the patient was bacteremic at Screening, the bacteremia has also resolved. Presumed eradication where, repeat cultures were not performed/clinically indicated in a patient who had a clinical response of cure (specific to cIAI population).
Per-pathogen Microbiological Response of Gram-negative Pathogen at TOC by CAZ-AVI MIC in mMITT Analysis Set
Proportion of patients with a favorable per-pathogen microbiological response for pathogens (>=10% of frequncy in the combined cIAI and cUTI patients): favourable microbiological response includes: Eradication Absence (or urine quantification less than 10^4 CFU/ml for cUTI patients) of causative pathogen from an appropriately obtained specimen at the site of infection. If the patient was bacteremic at Screening, the bacteremia has also resolved. Presumed eradication where, repeat cultures were not performed/clinically indicated in a patient who had a clinical response of cure (specific to cIAI population). For E.coli, MIC available values are: <=0.008, 0.03, 0.06, 0.12, 0.25, 0.5, 1, 2, 8. For K. pneumoniae, MIC available values are: 0.06, 0.12, 0.25, 0.5, 1, 2, 4, 32, >32. For P. aeruginosa, MIC available values are: 2, 4, 8, 16, 32, >32.
Per-pathogen Microbiological Response of Gram-negative Pathogen at TOC by CAZ-AVI MIC in EME at TOC Analysis Set
Proportion of patients with a favorable per-pathogen microbiological response for pathogens (>=10% of frequncy in the combined cIAI and cUTI patients): favourable microbiological response includes: Eradication Absence (or urine quantification less than 10^4 CFU/ml for cUTI patients) of causative pathogen from an appropriately obtained specimen at the site of infection. If the patient was bacteremic at Screening, the bacteremia has also resolved. Presumed eradication where, repeat cultures were not performed/clinically indicated in a patient who had a clinical response of cure (specific to cIAI population). For E.coli, MIC available values are: <=0.008, 0.03, 0.06, 0.12, 0.25, 0.5, 1, 2, 8. For K. pneumoniae, MIC available values are: 0.06, 0.12, 0.25, 0.5, 1, 2, 4, >32. For P. aeruginosa, MIC available values are: 2, 4, 8, 16, 32, >32.
The Reason for Treatment Change/Discontinuation in mMITT Analysis Set
Proportion of patients in the mMITT analysis set for whom the assigned study treatment was changed, discontinued, or interrupted. Creatinine clearance (CrCl)
The 28 Days All Cause Mortality Rate in mMITT Analysis Set
Proportion of patients with Day 28 all-cause mortality in mMITT analysis set. The death in the cIAI patient were reviewed independently by the SRP Chair.
The 28 Days All Cause Mortality Rate in EME at TOC Analysis Set
Proportion of patients with Day 28 all-cause mortality in EME at TOC analysis set. The death in the cIAI patient were reviewed independently by the SRP Chair.
Plasma Concentrations for Ceftazidime and Avibactam - cIAI in PK Analysis Set
Blood samples were taken on Day 3 for ceftazidime and avibactam plasma concentration.
Plasma Concentrations for Ceftazidime and Avibactam - cUTI in PK Analysis Set
Blood samples were taken on Day 3 for ceftazidime and avibactam plasma concentration.

Full Information

First Posted
June 28, 2012
Last Updated
August 31, 2017
Sponsor
Pfizer
Collaborators
Forest Laboratories
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1. Study Identification

Unique Protocol Identification Number
NCT01644643
Brief Title
Ceftazidime-Avibactam for the Treatment of Infections Due to Ceftazidime Resistant Pathogens
Official Title
An Open-Label, Randomized, Multicenter, Phase III Study of Ceftazidime Avibactam (CAZ-AVI, Formerly CAZ104) and Best Available Therapy for the Treatment of Infections Due to Ceftazidime Resistant Gram Negative Pathogens
Study Type
Interventional

2. Study Status

Record Verification Date
August 2017
Overall Recruitment Status
Completed
Study Start Date
January 2013 (undefined)
Primary Completion Date
September 2014 (Actual)
Study Completion Date
September 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Pfizer
Collaborators
Forest Laboratories

4. Oversight

5. Study Description

Brief Summary
To Evaluate the Effects of Ceftazidime-Avibactam and Best Available Therapy in patients with complicated urinary tract infections and complicated intra-abdominal infections.
Detailed Description
An Open-Label, Randomized, Multicenter, Phase III Study of Ceftazidime Avibactam (CAZ-AVI, formerly CAZ104) and Best Available Therapy for the Treatment of Infections Due to Ceftazidime Resistant Gram Negative Pathogens

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Complicated Urinary Tract Infection, Complicated Intra-abdominal Infection
Keywords
Ceftazidime,, avibactam,, metronidazone,, Anti-Infectives

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
345 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Ceftazidime - Avibactam ( CAZ-AVI)
Arm Type
Experimental
Arm Description
IV treatment
Arm Title
Best Available Therapy
Arm Type
Active Comparator
Arm Description
IV treatment
Intervention Type
Drug
Intervention Name(s)
Ceftazidime - Avibactam ( CAZ-AVI)
Intervention Description
Ceftazidime 2000 mg and 500 mg of avibactam Patients randomized to receive CAZ-AVI will receive an infusion of CAZ-AVI (2000 mg ceftazidime and 500 mg avibactam) every 8 hours administered by intravenous (IV) infusion in a volume of 100 mL at a constant rate over 120 minutes
Intervention Type
Drug
Intervention Name(s)
Best Available Therapy
Intervention Description
Patients randomized to receive Best Available Therapy will receive the best available standard of care (SOC) anti-infective therapy for their infection administered in accord with approved local label recommendation
Intervention Type
Drug
Intervention Name(s)
Metronidazole
Other Intervention Name(s)
Flagyl
Intervention Description
Anti-infective, 500 mg (cIAI only) Patients randomized to receive CAZ-AVI for cIAI will also receive metronidazole (500 mg) administered by IV infusion in a volume of 100 mL at a constant rate over 60 minutes immediately following the CAZ-AVI infusion
Primary Outcome Measure Information:
Title
Clinical Response at Test of Cure (TOC) in Microbiological Modified Intent-to-treat (mMITT) Analysis Set
Description
Proportion of patients with clinical cure at the TOC visit in the mMITT analysis set. Clinical cure: Complete resolution or significant improvement of signs and symptoms of the index infection such that no further antibacterial therapy (other than those allowed per protocol) is necessary; for cIAI patients no drainage or surgical intervention after 96 hours from randomization is necessary (ie. drainage or surgical intervention up to 96 hours from randomization is permissible).
Time Frame
6-12 days after last infusion of study therapy. Duration of study therapy was 5 to 21 days.
Secondary Outcome Measure Information:
Title
Clinical Response at End of Treatment (EOT) in mMITT Analysis Set.
Description
Proportion of patients with clinical cure at the EOT visit in the mMITT analysis set. Clinical cure: Complete resolution or significant improvement of signs and symptoms of the index infection such that no further antibacterial therapy (other than those allowed per protocol) is necessary; for cIAI patients no drainage or surgical intervention after 96 hours from randomization is necessary (ie. drainage or surgical intervention up to 96 hours from randomization is permissible).
Time Frame
28 hours after completion of last infusion of study therapy. Duration of study therapy was 5 to 21 days.
Title
Clinical Response at Follow-up 1 (FU1) in mMITT Analysis Set
Description
Proportion of patients with clinical cure at the FU1 visit in the mMITT analysis set. Clinical cure: Complete resolution or significant improvement of signs and symptoms of the index infection such that no further antibacterial therapy (other than those allowed per protocol) is necessary; for cIAI patients no drainage or surgical intervention after 96 hours from randomization is necessary (ie. drainage or surgical intervention up to 96 hours from randomization is permissible).
Time Frame
cIAI: 27-37 calendar days from randomization/cUTI: 20-27 calendar days from randomization
Title
Clinical Response at Follow-up 2 (FU2) in mMITT Analysis Set
Description
Proportion of patients with clinical cure at the FU2 visit in the mMITT analysis set. Clinical cure: Complete resolution or significant improvement of signs and symptoms of the index infection such that no further antibacterial therapy (other than those allowed per protocol) is necessary; for cIAI patients no drainage or surgical intervention after 96 hours from randomization is necessary (ie. drainage or surgical intervention up to 96 hours from randomization is permissible).
Time Frame
At FU2, data was only collected for the cUTI Arms: 28-34 calendar days from randomization
Title
Clinical Response at EOT in Extended Microbiologically Evaluable (EME) at EOT Analysis Set.
Description
Proportion of patients with clinical cure at the EOT visit in the EME at EOT analysis set. Clinical cure: Complete resolution or significant improvement of signs and symptoms of the index infection such that no further antibacterial therapy (other than those allowed per protocol) is necessary; for cIAI patients no drainage or surgical intervention after 96 hours from randomization is necessary (ie. drainage or surgical intervention up to 96 hours from randomization is permissible).
Time Frame
28 hours after completion of last infusion of study therapy. Duration of study therapy was 5 to 21 days.
Title
Clinical Response at TOC in EME at TOC Analysis Set.
Description
Proportion of patients with clinical cure at the TOC visit in the EME at TOC analysis set. Clinical cure: Complete resolution or significant improvement of signs and symptoms of the index infection such that no further antibacterial therapy (other than those allowed per protocol) is necessary; for cIAI patients no drainage or surgical intervention after 96 hours from randomization is necessary (ie. drainage or surgical intervention up to 96 hours from randomization is permissible).
Time Frame
6-12 days after last infusion of study therapy.Duration of study therapy was 5 to 21 days.
Title
Clinical Response at FU1 in EME at FU1 Analysis Set.
Description
Proportion of patients with clinical cure at the FU1 visit in EME at FU1 analysis set. Clinical cure: Complete resolution or significant improvement of signs and symptoms of the index infection such that no further antibacterial therapy (other than those allowed per protocol) is necessary; for cIAI patients no drainage or surgical intervention after 96 hours from randomization is necessary (ie. drainage or surgical intervention up to 96 hours from randomization is permissible).
Time Frame
cIAI: 27-37 calendar days from randomization/cUTI: 20-27 calendar days from randomization
Title
Clinical Response at FU2 in EME at FU2 Analysis Set
Description
Proportion of patients with clinical cure at the FU2 visit in EME at FU2 analysis set. Clinical cure: Complete resolution or significant improvement of signs and symptoms of the index infection such that no further antibacterial therapy (other than those allowed per protocol) is necessary.
Time Frame
At FU2, data was only collected for the cUTI Arms: 28-34 calendar days from randomization
Title
Clinical Cure at TOC by Baseline Gram-negative Pathogen in mMITT Analysis Set
Description
Proportion of patients with clinical cure at TOC visit by baseline pathogen (>=10% of frequency in the combined cIAI and cUTI patients) in the mMITT analysis set. Clinical cure: Complete resolution or significant improvement of signs and symptoms of the index infection such that no further antibacterial therapy (other than those allowed per protocol) is necessary; for cIAI patients no drainage or surgical intervention after 96 hours from randomization is necessary (ie. drainage or surgical intervention up to 96 hours from randomization is permissible).
Time Frame
6-12 days after last infusion of study therapy.Duration of study therapy was 5 to 21 days.
Title
Clinical Cure at TOC by Baseline Gram-negative Pathogen in EME at TOC Analysis Set
Description
Proportion of patients with clinical cure at TOC visit by baseline Gram-negative pathogen (>=10% of frequency in the combined cIAI and cUTI patients) in EME at TOC analysis set. Clinical cure: Complete resolution or significant improvement of signs and symptoms of the index infection such that no further antibacterial therapy (other than those allowed per protocol) is necessary; for cIAI patients no drainage or surgical intervention after 96 hours from randomization is necessary (ie. drainage or surgical intervention up to 96 hours from randomization is permissible).
Time Frame
6-12 days after last infusion of study therapy.Duration of study therapy was 5 to 21 days.
Title
Clinical Cure at TOC by Previously Failed Treatment Class in mMITT Analysis Set
Description
Proportion of patients with clinical cure at TOC visit by previously failed treatment class in the mMITT analysis set. Clinical cure: Complete resolution or significant improvement of signs and symptoms of the index infection such that no further antibacterial therapy (other than those allowed per protocol) is necessary; for cIAI patients no drainage or surgical intervention after 96 hours from randomization is necessary (ie. drainage or surgical intervention up to 96 hours from randomization is permissible).
Time Frame
6-12 days after last infusion of study therapy. Duration of study therapy was 5 to 21 days.
Title
Clinical Cure at EOT by Previously Failed Treatment Class in EME at EOT Analysis Set
Description
Proportion of patients with clinical cure at EOT visit by previously failed treatment class in EME at EOT analysis set. Clinical cure: Complete resolution or significant improvement of signs and symptoms of the index infection such that no further antibacterial therapy (other than those allowed per protocol) is necessary; for cIAI patients no drainage or surgical intervention after 96 hours from randomization is necessary (ie. drainage or surgical intervention up to 96 hours from randomization is permissible).
Time Frame
28 hours after completion of last infusion of study therapy.Duration of study therapy was 5 to 21 days.
Title
Clinical Cure at TOC by Previously Failed Treatment Class in EME at TOC Analysis Set
Description
Proportion of patients with clinical cure at TOC visit by previously failed treatment class in EME at TOC analysis set. Clinical cure: Complete resolution or significant improvement of signs and symptoms of the index infection such that no further antibacterial therapy (other than those allowed per protocol) is necessary; for cIAI patients no drainage or surgical intervention after 96 hours from randomization is necessary (ie. drainage or surgical intervention up to 96 hours from randomization is permissible).
Time Frame
6-12 days after last infusion of study therapy. Duration of study therapy was 5 to 21 days.
Title
Clinical Cure at FU1 by Previously Failed Treatment Class in EME at FU1 Analysis Set
Description
Proportion of patients with clinical cure at FU1 visit by previously failed treatment class in EME at FU1 analysis set. Clinical cure: Complete resolution or significant improvement of signs and symptoms of the index infection such that no further antibacterial therapy (other than those allowed per protocol) is necessary; for cIAI patients no drainage or surgical intervention after 96 hours from randomization is necessary (ie. drainage or surgical intervention up to 96 hours from randomization is permissible).
Time Frame
cIAI: 27-37 calendar days from randomization/cUTI: 20-27 calendar days from randomization
Title
Clinical Cure at FU2 by Previously Failed Treatment Class in EME at FU2 Analysis Set
Description
Proportion of patients with clinical cure at FU2 visit by previously failed treatment class in EME at FU2 analysis set. Clinical cure: Complete resolution or significant improvement of signs and symptoms of the index infection such that no further antibacterial therapy (other than those allowed per protocol) is necessary.
Time Frame
At FU2, data was only collected for the cUTI Arms: 28-34 calendar days from randomization
Title
Per-patient Microbiological Response at EOT in mMITT Analysis Set
Description
Microbiological responses as per the protocoled criteria: responses other than "indeterminate" were classified as "favorable" or "unfavorable." Favorable microbiological response assessments included "eradication" and "presumed eradication." Unfavorable microbiological response assessments included "persistence," "persistence with increasing minimum inhibitory concentration (MIC)," and "presumed persistence." Indeterminate microbiologic response assessments included cIAI patients where the clinical response was changed to indeterminate due to a Surgical Review Panel assessment of inadequate source control (ie, circumstances that preclude classification as eradication, presumed eradication, persistence, persistence with increasing MIC, and presumed persistence).
Time Frame
28 hours after completion of last infusion of study therapy. Duration of study therapy was 5 to 21 days.
Title
Per-patient Microbiological Response at TOC in mMITT Analysis Set
Description
Microbiological responses as per the protocoled criteria: responses other than "indeterminate" were classified as "favorable" or "unfavorable." Favorable microbiological response assessments included "eradication" and "presumed eradication." Unfavorable microbiological response assessments included "persistence," "persistence with increasing minimum inhibitory concentration (MIC)," and "presumed persistence." Indeterminate microbiologic response assessments included cIAI patients where the clinical response was changed to indeterminate due to a Surgical Review Panel assessment of inadequate source control (ie, circumstances that preclude classification as eradication, presumed eradication, persistence, persistence with increasing MIC, and presumed persistence).
Time Frame
6-12 days after last infusion of study therapy. Duration of study therapy was 5 to 21 days.
Title
Per-patient Microbiological Response at FU1 in mMITT Analysis Set
Description
Microbiological responses as per the protocoled criteria: responses other than "indeterminate" were classified as "favorable" or "unfavorable." Favorable microbiological response assessments included "eradication" and "presumed eradication." Unfavorable microbiological response assessments included "persistence," "persistence with increasing minimum inhibitory concentration (MIC)," and "presumed persistence." Indeterminate microbiologic response assessments included cIAI patients where the clinical response was changed to indeterminate due to a Surgical Review Panel assessment of inadequate source control (ie, circumstances that preclude classification as eradication, presumed eradication, persistence, persistence with increasing MIC, and presumed persistence).
Time Frame
cUTI: 20-27 calendar days from randomization/cIAI: 27-37 calendar days from randomization
Title
Per-patient Microbiological Response at FU2 in mMITT Analysis Set
Description
Microbiological responses as per the protocoled criteria: responses other than "indeterminate" were classified as "favorable" or "unfavorable." Favorable microbiological response assessments included "eradication" and "presumed eradication." Unfavorable microbiological response assessments included "persistence," "persistence with increasing minimum inhibitory concentration (MIC)," and "presumed persistence." Indeterminate microbiologic response assessments included cIAI patients where the clinical response was changed to indeterminate due to a Surgical Review Panel assessment of inadequate source control (ie, circumstances that preclude classification as eradication, presumed eradication, persistence, persistence with increasing MIC, and presumed persistence).
Time Frame
At FU2, data was only collected for the cUTI Arms: 28-34 calendar days from randomization
Title
Per-patient Microbiological Response at EOT in EME at EOT Analysis Set
Description
Microbiological responses as per the protocoled criteria: responses other than "indeterminate" were classified as "favorable" or "unfavorable." Favorable microbiological response assessments included "eradication" and "presumed eradication." Unfavorable microbiological response assessments included "persistence," "persistence with increasing minimum inhibitory concentration (MIC)," and "presumed persistence." Indeterminate microbiologic response assessments included cIAI patients where the clinical response was changed to indeterminate due to a Surgical Review Panel assessment of inadequate source control (ie, circumstances that preclude classification as eradication, presumed eradication, persistence, persistence with increasing MIC, and presumed persistence).
Time Frame
28 hours after completion of last infusion of study therapy. Duration of study therapy was 5 to 21 days.
Title
Per-patient Microbiological Response at TOC in EME at TOC Analysis Set
Description
Microbiological responses as per the protocoled criteria: responses other than "indeterminate" were classified as "favorable" or "unfavorable." Favorable microbiological response assessments included "eradication" and "presumed eradication." Unfavorable microbiological response assessments included "persistence," "persistence with increasing minimum inhibitory concentration (MIC)," and "presumed persistence." Indeterminate microbiologic response assessments included cIAI patients where the clinical response was changed to indeterminate due to a Surgical Review Panel assessment of inadequate source control (ie, circumstances that preclude classification as eradication, presumed eradication, persistence, persistence with increasing MIC, and presumed persistence).
Time Frame
6-12 days after last infusion of study therapy.Duration of study therapy was 5 to 21 days.
Title
Per-patient Microbiological Response at FU1 in EME at FU1 Analysis Set
Description
Microbiological responses as per the protocoled criteria: responses other than "indeterminate" were classified as "favorable" or "unfavorable." Favorable microbiological response assessments included "eradication" and "presumed eradication." Unfavorable microbiological response assessments included "persistence," "persistence with increasing minimum inhibitory concentration (MIC)," and "presumed persistence." Indeterminate microbiologic response assessments included cIAI patients where the clinical response was changed to indeterminate due to a Surgical Review Panel assessment of inadequate source control (ie, circumstances that preclude classification as eradication, presumed eradication, persistence, persistence with increasing MIC, and presumed persistence).
Time Frame
cUTI: 20-27 calendar days from randomization/cIAI: 27-37 calendar days from randomization
Title
Per-patient Microbiological Response at FU2 in EME at FU2 Analysis Set
Description
Microbiological responses as per the protocoled criteria: responses other than "indeterminate" were classified as "favorable" or "unfavorable." Favorable microbiological response assessments included "eradication" and "presumed eradication." Unfavorable microbiological response assessments included "persistence," "persistence with increasing minimum inhibitory concentration (MIC)," and "presumed persistence." Indeterminate microbiologic response assessments included cIAI patients where the clinical response was changed to indeterminate due to a Surgical Review Panel assessment of inadequate source control (ie, circumstances that preclude classification as eradication, presumed eradication, persistence, persistence with increasing MIC, and presumed persistence).
Time Frame
At FU2, data was only collected for the cUTI Arms: 28-34 calendar days from randomization
Title
Per-pathogen Microbiological Response of Gram-negative Pathogen at EOT in mMITT Analysis Set
Description
Proportion of patients with a favorable per-pathogen microbiological response for pathogens (>=10% of frequency in the combined cIAI and cUTI patients): favourable microbiological response includes: Eradication Absence (or urine quantification less than 10^4 CFU/ml for cUTI patients) of causative pathogen from an appropriately obtained specimen at the site of infection. If the patient was bacteremic at Screening, the bacteremia has also resolved. Presumed eradication where, repeat cultures were not performed/clinically indicated in a patient who had a clinical response of cure (specific to cIAI population).
Time Frame
28 hours after completion of last infusion of study therapy. Duration of study therapy was 5 to 21 days.
Title
Per-pathogen Microbiological Response of Gram-negative Pathogen at TOC in mMITT Analysis Set
Description
Proportion of patients with a favorable per-pathogen microbiological response for pathogens (>=10% of frequency in the combined cIAI and cUTI patients): favourable microbiological response includes: Eradication Absence (or urine quantification less than 10^4 CFU/ml for cUTI patients) of causative pathogen from an appropriately obtained specimen at the site of infection. If the patient was bacteremic at Screening, the bacteremia has also resolved. Presumed eradication where, repeat cultures were not performed/clinically indicated in a patient who had a clinical response of cure (specific to cIAI population).
Time Frame
6-12 days after last infusion of study therapy. Duration of study therapy was 5 to 21 days.
Title
Per-pathogen Microbiological Response of Gram-negative Pathogen at FU1 in mMITT Analysis Set
Description
Proportion of patients with a favorable per-pathogen microbiological response for pathogens (>=10% of frequency in the combined cIAI and cUTI patients): favourable microbiological response includes: Eradication Absence (or urine quantification less than 10^4 CFU/ml for cUTI patients) of causative pathogen from an appropriately obtained specimen at the site of infection. If the patient was bacteremic at Screening, the bacteremia has also resolved. Presumed eradication where, repeat cultures were not performed/clinically indicated in a patient who had a clinical response of cure (specific to cIAI population).
Time Frame
cIAI: 27-37 calendar days from randomization/cUTI: 20-27 calendar days from randomization
Title
Per-pathogen Microbiological Response of Gram-negative Pathogen at FU2 in mMITT Analysis Set
Description
Proportion of patients with a favorable per-pathogen microbiological response for pathogens (>=10% of frequncy in the combined cIAI and cUTI patients): favourable microbiological response includes: Eradication Absence (or urine quantification less than 10^4 CFU/ml for cUTI patients) of causative pathogen from an appropriately obtained specimen at the site of infection. If the patient was bacteremic at Screening, the bacteremia has also resolved. Presumed eradication where, repeat cultures were not performed/clinically indicated in a patient who had a clinical response of cure (specific to cIAI population).
Time Frame
At FU2, data was only collected for the cUTI Arms: 28-34 calendar days from randomization
Title
Per-pathogen Microbiological Response of Gram-negative Pathogen at EOT in EME at EOT Analysis Set
Description
Proportion of patients with a favorable per-pathogen microbiological response for pathogens (>=10% of frequncy in the combined cIAI and cUTI patients): favourable microbiological response includes: Eradication Absence (or urine quantification less than 10^4 CFU/ml for cUTI patients) of causative pathogen from an appropriately obtained specimen at the site of infection. If the patient was bacteremic at Screening, the bacteremia has also resolved. Presumed eradication where, repeat cultures were not performed/clinically indicated in a patient who had a clinical response of cure (specific to cIAI population).
Time Frame
28 hours after completion of last infusion of study therapy. Duration of study therapy was 5 to 21 days.
Title
Per-pathogen Microbiological Response of Gram-negative Pathogen at TOC in EME at TOC Analysis Set
Description
Proportion of patients with a favorable per-pathogen microbiological response for pathogens (>=10% of frequncy in the combined cIAI and cUTI patients): favourable microbiological response includes: Eradication Absence (or urine quantification less than 10^4 CFU/ml for cUTI patients) of causative pathogen from an appropriately obtained specimen at the site of infection. If the patient was bacteremic at Screening, the bacteremia has also resolved. Presumed eradication where, repeat cultures were not performed/clinically indicated in a patient who had a clinical response of cure (specific to cIAI population).
Time Frame
6-12 days after last infusion of study therapy. Duration of study therapy was 5 to 21 days.
Title
Per-pathogen Microbiological Response of Gram-negative Pathogen at FU1 in EME at FU1 Analysis Set
Description
Proportion of patients with a favorable per-pathogen microbiological response for pathogens (>=10% of frequncy in the combined cIAI and cUTI patients): favourable microbiological response includes: Eradication Absence (or urine quantification less than 10^4 CFU/ml for cUTI patients) of causative pathogen from an appropriately obtained specimen at the site of infection. If the patient was bacteremic at Screening, the bacteremia has also resolved. Presumed eradication where, repeat cultures were not performed/clinically indicated in a patient who had a clinical response of cure (specific to cIAI population).
Time Frame
cIAI: 27-37 calendar days from randomization/cUTI: 20-27 calendar days from randomization
Title
Per-pathogen Microbiological Response of Gram-negative Pathogen at FU2 in EME at FU2 Analysis Set
Description
Proportion of patients with a favorable per-pathogen microbiological response for pathogens (>=10% of frequncy in the combined cIAI and cUTI patients): favourable microbiological response includes: Eradication Absence (or urine quantification less than 10^4 CFU/ml for cUTI patients) of causative pathogen from an appropriately obtained specimen at the site of infection. If the patient was bacteremic at Screening, the bacteremia has also resolved. Presumed eradication where, repeat cultures were not performed/clinically indicated in a patient who had a clinical response of cure (specific to cIAI population).
Time Frame
At FU2, data was only collected for the cUTI Arms: 28-34 calendar days from randomization
Title
Per-pathogen Microbiological Response of Gram-negative Pathogen at TOC by CAZ-AVI MIC in mMITT Analysis Set
Description
Proportion of patients with a favorable per-pathogen microbiological response for pathogens (>=10% of frequncy in the combined cIAI and cUTI patients): favourable microbiological response includes: Eradication Absence (or urine quantification less than 10^4 CFU/ml for cUTI patients) of causative pathogen from an appropriately obtained specimen at the site of infection. If the patient was bacteremic at Screening, the bacteremia has also resolved. Presumed eradication where, repeat cultures were not performed/clinically indicated in a patient who had a clinical response of cure (specific to cIAI population). For E.coli, MIC available values are: <=0.008, 0.03, 0.06, 0.12, 0.25, 0.5, 1, 2, 8. For K. pneumoniae, MIC available values are: 0.06, 0.12, 0.25, 0.5, 1, 2, 4, 32, >32. For P. aeruginosa, MIC available values are: 2, 4, 8, 16, 32, >32.
Time Frame
6-12 days after last infusion of study therapy. Duration of study therapy was 5 to 21 days.
Title
Per-pathogen Microbiological Response of Gram-negative Pathogen at TOC by CAZ-AVI MIC in EME at TOC Analysis Set
Description
Proportion of patients with a favorable per-pathogen microbiological response for pathogens (>=10% of frequncy in the combined cIAI and cUTI patients): favourable microbiological response includes: Eradication Absence (or urine quantification less than 10^4 CFU/ml for cUTI patients) of causative pathogen from an appropriately obtained specimen at the site of infection. If the patient was bacteremic at Screening, the bacteremia has also resolved. Presumed eradication where, repeat cultures were not performed/clinically indicated in a patient who had a clinical response of cure (specific to cIAI population). For E.coli, MIC available values are: <=0.008, 0.03, 0.06, 0.12, 0.25, 0.5, 1, 2, 8. For K. pneumoniae, MIC available values are: 0.06, 0.12, 0.25, 0.5, 1, 2, 4, >32. For P. aeruginosa, MIC available values are: 2, 4, 8, 16, 32, >32.
Time Frame
6-12 days after last infusion of study therapy. Duration of study therapy was 5 to 21 days.
Title
The Reason for Treatment Change/Discontinuation in mMITT Analysis Set
Description
Proportion of patients in the mMITT analysis set for whom the assigned study treatment was changed, discontinued, or interrupted. Creatinine clearance (CrCl)
Time Frame
From first infusion to last infusion of study therapy. Duration of study therapy was 5 to 21 days.
Title
The 28 Days All Cause Mortality Rate in mMITT Analysis Set
Description
Proportion of patients with Day 28 all-cause mortality in mMITT analysis set. The death in the cIAI patient were reviewed independently by the SRP Chair.
Time Frame
From first infusion to Day 28
Title
The 28 Days All Cause Mortality Rate in EME at TOC Analysis Set
Description
Proportion of patients with Day 28 all-cause mortality in EME at TOC analysis set. The death in the cIAI patient were reviewed independently by the SRP Chair.
Time Frame
From first infusion to Day 28
Title
Plasma Concentrations for Ceftazidime and Avibactam - cIAI in PK Analysis Set
Description
Blood samples were taken on Day 3 for ceftazidime and avibactam plasma concentration.
Time Frame
Anytime within 15 minutes prior to or after stopping study drug, anytime between 30 to 90 minutes after stopping study drug, anytime between 300 to 360 minutes after stopping study drug
Title
Plasma Concentrations for Ceftazidime and Avibactam - cUTI in PK Analysis Set
Description
Blood samples were taken on Day 3 for ceftazidime and avibactam plasma concentration.
Time Frame
Anytime within 15 minutes prior to or after stopping study drug, anytime between 30 to 90 minutes after stopping study drug, anytime between 300 to 360 minutes after stopping study drug

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
90 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patient must be ≥18 and ≤90 years of age Female patients can participate if they are surgically sterile or completed menopause or females capable of having children and agree not to attempt pregnancy while receiving IV study therapy and for a period of 7 days after Patient has a ceftazidime-resistant Gram negative pathogen that was isolated from an appropriate culture within 5 days prior to study entry (ie, within 5 days prior to Screening; the study-qualifying culture), which was determined to be the causative agent of the entry infection Exclusion Criteria: Patient has an APACHE II score >30 (cIAI patients only) Patient has an infection due to Gram negative pathogen that is unlikely to respond to CAZ-AVI treatment (eg, Acinetobacter spp., Stenotrophomonas spp.) Patient is receiving hemodialysis or peritoneal dialysis or had a renal transplant Patient is immunocompromised Patient has a rapidly progressive or terminal illness with a high risk of mortality due to any cause, including acute hepatic failure, respiratory failure or severe septic shock such that they are unlikely to survive the 4- to 5-week study period.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Paul Newell, MBBS, MRCP
Organizational Affiliation
AstraZeneca
Official's Role
Study Director
Facility Information:
Facility Name
Research Site
City
Shreveport
State/Province
Louisiana
Country
United States
Facility Name
Research Site
City
Lima
State/Province
Ohio
Country
United States
Facility Name
Research Site
City
El Talar
Country
Argentina
Facility Name
Research Site
City
La Plata
Country
Argentina
Facility Name
Research Site
City
Pazardzhik
Country
Bulgaria
Facility Name
Research Site
City
Pleven
Country
Bulgaria
Facility Name
Research Site
City
Ruse
Country
Bulgaria
Facility Name
Research Site
City
Sofia
Country
Bulgaria
Facility Name
Research Site
City
Varna
Country
Bulgaria
Facility Name
Research Site
City
Veliko Turnovo
Country
Bulgaria
Facility Name
Research Site
City
Slavonski Brod
Country
Croatia
Facility Name
Research Site
City
Zagreb
Country
Croatia
Facility Name
Research Site
City
Praha 5
Country
Czechia
Facility Name
Research Site
City
Tours
Country
France
Facility Name
Research Site
City
Nazareth
Country
Israel
Facility Name
Research Site
City
Petach Tikva
Country
Israel
Facility Name
Research Site
City
Ramat-Gan
Country
Israel
Facility Name
Research Site
City
Tel Aviv
Country
Israel
Facility Name
Research Site
City
Seoul
Country
Korea, Republic of
Facility Name
Research Site
City
Guadalajara
Country
Mexico
Facility Name
Research Site
City
Mexico, Distrito Federal
Country
Mexico
Facility Name
Research Site
City
Cusco
Country
Peru
Facility Name
Research Site
City
Surco
Country
Peru
Facility Name
Research Site
City
Manila
Country
Philippines
Facility Name
Research Site
City
Szczecin
Country
Poland
Facility Name
Research Site
City
Bucharest
Country
Romania
Facility Name
Research Site
City
Bucuresti
Country
Romania
Facility Name
Research Site
City
Irkutsk
Country
Russian Federation
Facility Name
Research Site
City
Krasnodar
Country
Russian Federation
Facility Name
Research Site
City
Novosibirsk
Country
Russian Federation
Facility Name
Research Site
City
Penza
Country
Russian Federation
Facility Name
Research Site
City
Saint-Petersburg
Country
Russian Federation
Facility Name
Research Site
City
St. Petersburg
Country
Russian Federation
Facility Name
Research Site
City
St.-Petersburg,
Country
Russian Federation
Facility Name
Research Site
City
Yaroslavl
Country
Russian Federation
Facility Name
Research Site
City
Johannesburg
Country
South Africa
Facility Name
Research Site
City
Barcelona
Country
Spain
Facility Name
Research Site
City
Madrid
Country
Spain
Facility Name
Research Site
City
Ankara
Country
Turkey
Facility Name
Research Site
City
Antalya
Country
Turkey
Facility Name
Research Site
City
Diyarbakir
Country
Turkey
Facility Name
Research Site
City
Istanbul
Country
Turkey
Facility Name
Research Site
City
Dnipropetrovsk
Country
Ukraine
Facility Name
Research Site
City
Kharkiv
Country
Ukraine
Facility Name
Research Site
City
Kyiv
Country
Ukraine
Facility Name
Research Site
City
Zaporizhzhya
Country
Ukraine

12. IPD Sharing Statement

Citations:
PubMed Identifier
27107460
Citation
Carmeli Y, Armstrong J, Laud PJ, Newell P, Stone G, Wardman A, Gasink LB. Ceftazidime-avibactam or best available therapy in patients with ceftazidime-resistant Enterobacteriaceae and Pseudomonas aeruginosa complicated urinary tract infections or complicated intra-abdominal infections (REPRISE): a randomised, pathogen-directed, phase 3 study. Lancet Infect Dis. 2016 Jun;16(6):661-673. doi: 10.1016/S1473-3099(16)30004-4. Epub 2016 Apr 20.
Results Reference
background
PubMed Identifier
32602065
Citation
Cheng K, Newell P, Chow JW, Broadhurst H, Wilson D, Yates K, Wardman A. Safety Profile of Ceftazidime-Avibactam: Pooled Data from the Adult Phase II and Phase III Clinical Trial Programme. Drug Saf. 2020 Aug;43(8):751-766. doi: 10.1007/s40264-020-00934-3.
Results Reference
derived
PubMed Identifier
30910899
Citation
Mendes RE, Castanheira M, Woosley LN, Stone GG, Bradford PA, Flamm RK. Characterization of beta-Lactamase Content of Ceftazidime-Resistant Pathogens Recovered during the Pathogen-Directed Phase 3 REPRISE Trial for Ceftazidime-Avibactam: Correlation of Efficacy against beta-Lactamase Producers. Antimicrob Agents Chemother. 2019 May 24;63(6):e02655-18. doi: 10.1128/AAC.02655-18. Print 2019 Jun.
Results Reference
derived
PubMed Identifier
30221827
Citation
Li J, Lovern M, Green ML, Chiu J, Zhou D, Comisar C, Xiong Y, Hing J, MacPherson M, Wright JG, Riccobene T, Carrothers TJ, Das S. Ceftazidime-Avibactam Population Pharmacokinetic Modeling and Pharmacodynamic Target Attainment Across Adult Indications and Patient Subgroups. Clin Transl Sci. 2019 Mar;12(2):151-163. doi: 10.1111/cts.12585. Epub 2018 Sep 28.
Results Reference
derived
PubMed Identifier
30061279
Citation
Nichols WW, Stone GG, Newell P, Broadhurst H, Wardman A, MacPherson M, Yates K, Riccobene T, Critchley IA, Das S. Ceftazidime-Avibactam Susceptibility Breakpoints against Enterobacteriaceae and Pseudomonas aeruginosa. Antimicrob Agents Chemother. 2018 Oct 24;62(11):e02590-17. doi: 10.1128/AAC.02590-17. Print 2018 Nov.
Results Reference
derived
PubMed Identifier
29912399
Citation
Stone GG, Newell P, Gasink LB, Broadhurst H, Wardman A, Yates K, Chen Z, Song J, Chow JW. Clinical activity of ceftazidime/avibactam against MDR Enterobacteriaceae and Pseudomonas aeruginosa: pooled data from the ceftazidime/avibactam Phase III clinical trial programme. J Antimicrob Chemother. 2018 Sep 1;73(9):2519-2523. doi: 10.1093/jac/dky204.
Results Reference
derived
PubMed Identifier
27872067
Citation
Stone GG, Bradford PA, Newell P, Wardman A. In Vitro Activity of Ceftazidime-Avibactam against Isolates in a Phase 3 Open-Label Clinical Trial for Complicated Intra-Abdominal and Urinary Tract Infections Caused by Ceftazidime-Nonsusceptible Gram-Negative Pathogens. Antimicrob Agents Chemother. 2017 Jan 24;61(2):e01820-16. doi: 10.1128/AAC.01820-16. Print 2017 Feb.
Results Reference
derived
Available IPD and Supporting Information:
Available IPD/Information Type
Study Protocol
Available IPD/Information URL
http://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_MED_7111&studyid=1452&filename=Clinical%20Study%20Protocol_3%20Redacted%20amended.pdf
Available IPD/Information Identifier
D4280C00006
Available IPD/Information Comments
D4280C00006 Clinical Study Protocol
Available IPD/Information Type
Study Protocol
Available IPD/Information URL
http://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_MED_7111&studyid=1452&filename=Clinical%20Study%20Protocol%20Amendment%202%20Redacted%20amended.pdf
Available IPD/Information Identifier
D4280C00006
Available IPD/Information Comments
D4280C00006 Clinical Study Protocol Amendment 2 Redacted amended
Available IPD/Information Type
Study Protocol
Available IPD/Information URL
http://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_MED_7111&studyid=1452&filename=Clinical%20Study%20Protocol%20Amendment%203%20Redacted%20amended.pdf
Available IPD/Information Identifier
D4280C00006
Available IPD/Information Comments
D4280C00006 Clinical Study Protocol Amendment 3 Redacted amended

Learn more about this trial

Ceftazidime-Avibactam for the Treatment of Infections Due to Ceftazidime Resistant Pathogens

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