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

This study has been completed.
Sponsor:
Collaborator:
Forest Laboratories
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT01644643
First received: June 28, 2012
Last updated: July 19, 2016
Last verified: June 2016
  Purpose
To Evaluate the Effects of Ceftazidime-Avibactam and Best Available Therapy in patients with complicated urinary tract infections and complicated intra-abdominal infections.

Condition Intervention Phase
Complicated Urinary Tract Infection,
Complicated Intra-abdominal Infection
Drug: Ceftazidime - Avibactam ( CAZ-AVI)
Drug: Best Available Therapy
Drug: Metronidazole
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by AstraZeneca:

Primary Outcome Measures:
  • Clinical Response at Test of Cure (TOC) in Microbiological Modified Intent-to-treat (mMITT) Analysis Set [ Time Frame: 6-12 days after last infusion of study therapy. Duration of study therapy was 5 to 21 days. ] [ Designated as safety issue: No ]
    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. [ Time Frame: 28 hours after completion of last infusion of study therapy. Duration of study therapy was 5 to 21 days. ] [ Designated as safety issue: No ]
    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 [ Time Frame: cIAI: 27-37 calendar days from randomization/cUTI: 20-27 calendar days from randomization ] [ Designated as safety issue: No ]
    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 [ Time Frame: At FU2, data was only collected for the cUTI Arms: 28-34 calendar days from randomization ] [ Designated as safety issue: No ]
    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. [ Time Frame: 28 hours after completion of last infusion of study therapy. Duration of study therapy was 5 to 21 days. ] [ Designated as safety issue: No ]
    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. [ Time Frame: 6-12 days after last infusion of study therapy.Duration of study therapy was 5 to 21 days. ] [ Designated as safety issue: No ]
    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. [ Time Frame: cIAI: 27-37 calendar days from randomization/cUTI: 20-27 calendar days from randomization ] [ Designated as safety issue: No ]
    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 [ Time Frame: At FU2, data was only collected for the cUTI Arms: 28-34 calendar days from randomization ] [ Designated as safety issue: No ]
    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 [ Time Frame: 6-12 days after last infusion of study therapy.Duration of study therapy was 5 to 21 days. ] [ Designated as safety issue: No ]
    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 [ Time Frame: 6-12 days after last infusion of study therapy.Duration of study therapy was 5 to 21 days. ] [ Designated as safety issue: No ]
    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 [ Time Frame: 6-12 days after last infusion of study therapy. Duration of study therapy was 5 to 21 days. ] [ Designated as safety issue: No ]
    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 [ Time Frame: 28 hours after completion of last infusion of study therapy.Duration of study therapy was 5 to 21 days. ] [ Designated as safety issue: No ]
    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 [ Time Frame: 6-12 days after last infusion of study therapy. Duration of study therapy was 5 to 21 days. ] [ Designated as safety issue: No ]
    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 [ Time Frame: cIAI: 27-37 calendar days from randomization/cUTI: 20-27 calendar days from randomization ] [ Designated as safety issue: No ]
    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 [ Time Frame: At FU2, data was only collected for the cUTI Arms: 28-34 calendar days from randomization ] [ Designated as safety issue: No ]
    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 [ Time Frame: 28 hours after completion of last infusion of study therapy. Duration of study therapy was 5 to 21 days. ] [ Designated as safety issue: No ]
    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 [ Time Frame: 6-12 days after last infusion of study therapy. Duration of study therapy was 5 to 21 days. ] [ Designated as safety issue: No ]
    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 [ Time Frame: cUTI: 20-27 calendar days from randomization/cIAI: 27-37 calendar days from randomization ] [ Designated as safety issue: No ]
    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 [ Time Frame: At FU2, data was only collected for the cUTI Arms: 28-34 calendar days from randomization ] [ Designated as safety issue: No ]
    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 [ Time Frame: 28 hours after completion of last infusion of study therapy. Duration of study therapy was 5 to 21 days. ] [ Designated as safety issue: No ]
    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 [ Time Frame: 6-12 days after last infusion of study therapy.Duration of study therapy was 5 to 21 days. ] [ Designated as safety issue: No ]
    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 [ Time Frame: cUTI: 20-27 calendar days from randomization/cIAI: 27-37 calendar days from randomization ] [ Designated as safety issue: No ]
    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 [ Time Frame: At FU2, data was only collected for the cUTI Arms: 28-34 calendar days from randomization ] [ Designated as safety issue: No ]
    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 [ Time Frame: 28 hours after completion of last infusion of study therapy. Duration of study therapy was 5 to 21 days. ] [ Designated as safety issue: No ]
    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 [ Time Frame: 6-12 days after last infusion of study therapy. Duration of study therapy was 5 to 21 days. ] [ Designated as safety issue: No ]
    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 [ Time Frame: cIAI: 27-37 calendar days from randomization/cUTI: 20-27 calendar days from randomization ] [ Designated as safety issue: No ]
    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 [ Time Frame: At FU2, data was only collected for the cUTI Arms: 28-34 calendar days from randomization ] [ Designated as safety issue: No ]
    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 [ Time Frame: 28 hours after completion of last infusion of study therapy. Duration of study therapy was 5 to 21 days. ] [ Designated as safety issue: No ]
    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 [ Time Frame: 6-12 days after last infusion of study therapy. Duration of study therapy was 5 to 21 days. ] [ Designated as safety issue: No ]
    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 [ Time Frame: cIAI: 27-37 calendar days from randomization/cUTI: 20-27 calendar days from randomization ] [ Designated as safety issue: No ]
    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 [ Time Frame: At FU2, data was only collected for the cUTI Arms: 28-34 calendar days from randomization ] [ Designated as safety issue: No ]
    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 [ Time Frame: 6-12 days after last infusion of study therapy. Duration of study therapy was 5 to 21 days. ] [ Designated as safety issue: No ]
    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 [ Time Frame: 6-12 days after last infusion of study therapy. Duration of study therapy was 5 to 21 days. ] [ Designated as safety issue: No ]
    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 [ Time Frame: From first infusion to last infusion of study therapy. Duration of study therapy was 5 to 21 days. ] [ Designated as safety issue: No ]
    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 [ Time Frame: From first infusion to Day 28 ] [ Designated as safety issue: No ]
    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 [ Time Frame: From first infusion to Day 28 ] [ Designated as safety issue: No ]
    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 [ 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 ] [ Designated as safety issue: No ]
    Blood samples were taken on Day 3 for ceftazidime and avibactam plasma concentration.

  • Plasma Concentrations for Ceftazidime and Avibactam — cUTI in PK Analysis Set [ 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 ] [ Designated as safety issue: No ]
    Blood samples were taken on Day 3 for ceftazidime and avibactam plasma concentration.


Enrollment: 345
Study Start Date: January 2013
Study Completion Date: September 2014
Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Ceftazidime - Avibactam ( CAZ-AVI)
IV treatment
Drug: Ceftazidime - Avibactam ( CAZ-AVI)
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
Drug: Metronidazole
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
Other Name: Flagyl
Active Comparator: Best Available Therapy
IV treatment
Drug: Best Available Therapy
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

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
  Eligibility

Ages Eligible for Study:   18 Years to 90 Years   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01644643

  Show 46 Study Locations
Sponsors and Collaborators
AstraZeneca
Forest Laboratories
Investigators
Study Director: Paul Newell, MBBS, MRCP AstraZeneca
  More Information

Publications:
Study Data/Documents: Study Protocol  This link exits the ClinicalTrials.gov site
Identifier: D4280C00006
D4280C00006 Clinical Study Protocol
Study Protocol  This link exits the ClinicalTrials.gov site
Identifier: D4280C00006
D4280C00006 Clinical Study Protocol Amendment 2 Redacted amended
Study Protocol  This link exits the ClinicalTrials.gov site
Identifier: D4280C00006
D4280C00006 Clinical Study Protocol Amendment 3 Redacted amended

Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT01644643     History of Changes
Other Study ID Numbers: D4280C00006  2012-000726-21 
Study First Received: June 28, 2012
Results First Received: September 28, 2015
Last Updated: July 19, 2016
Health Authority: Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
Australia: Department of Health and Ageing Therapeutic Goods Administration
Belgium: Federal Agency for Medicinal Products and Health Products
Brazil: National Health Surveillance Agency
Bulgaria: Bulgarian Drug Agency
Chile: Instituto de Salud Pública de Chile
Croatia: Ministry of Health and Social Care
Czech Republic: State Institute for Drug Control
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Federal Institute for Drugs and Medical Devices
Greece: National Organization of Medicines
Hungary: National Institute of Pharmacy
India: Drugs Controller General of India
Israel: Ministry of Health
Italy: National Institute of Health
Japan: Pharmaceuticals and Medical Devices Agency
Mexico: Federal Commission for Sanitary Risks Protection
Peru: Ministry of Health
Philippines: Bureau of Food and Drugs
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Romania: National Medicines Agency
Russia: Ministry of Health of the Russian Federation
South Africa: Medicines Control Council
South Korea: Korea Food and Drug Administration (KFDA)
Spain: Spanish Agency of Medicines
Taiwan : Food and Drug Administration
Turkey: Ministry of Health
Ukraine: State Pharmacological Center - Ministry of Health
United States: Food and Drug Administration

Keywords provided by AstraZeneca:
Ceftazidime,
avibactam,
metronidazone,
Anti-Infectives

Additional relevant MeSH terms:
Infection
Communicable Diseases
Urinary Tract Infections
Intraabdominal Infections
Urologic Diseases
Avibactam
Avibactam, ceftazidime drug combination
Metronidazole
Ceftazidime
Anti-Infective Agents
Antiprotozoal Agents
Antiparasitic Agents
Anti-Bacterial Agents
Beta-Lactamase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 21, 2016