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Ceftazidime-Avibactam Compared With Doripenem Followed by Oral Therapy for Hospitalized Adults With Complicated UTIs (Urinary Tract Infections)

This study has been completed.
Sponsor:
Collaborator:
Forest Laboratories
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT01599806
First received: May 15, 2012
Last updated: February 3, 2016
Last verified: February 2016
  Purpose
The purpose of this study is to evaluate the effects of Ceftazidime Avibactam compared to Doripenem for treating hospitalized patients with complicated urinary tract infections, including acute pyelonephritis

Condition Intervention Phase
Complicated Urinary Tract Infection (cUTI) Including Acute Pyelonephritis
Drug: Ceftazidime - Avibactam ( CAZ-AVI)
Drug: Doripenem
Drug: Either switch to oral therapy: 500 mg of Ciprofloxacin (oral)
Drug: or switch to oral therapy: 800 mg/160 mg of sulfamethoxazole/trimethoprim (oral)
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase III, Randomized, Multicenter, Double-Blind, Double Dummy, Parallel Group, Comparative Study to Determine the Efficacy, Safety, and Tolerability of Ceftazidime Avibactam (CAZ-AVI, Formerly CAZ104) Versus Doripenem Followed by Appropriate Oral Therapy in the Treatment of Complicated Urinary Tract Infections, Including Acute Pyelonephritis, With a Gram Negative Pathogen in Hospitalized Adults

Resource links provided by NLM:


Further study details as provided by AstraZeneca:

Primary Outcome Measures:
  • Patient-reported Symptomatic Response at Day 5 (mMITT Analysis Set): Non-inferiority Hypothesis Test [ Time Frame: At Day 5 visit. Day 5 visit is based on 24 hour periods from the first dose date and time. ] [ Designated as safety issue: No ]
    Number of patients with symptomatic resolution (or return to premorbid state) of UTI-specific symptoms except flank pain (frequency/urgency/dysuria/suprapubic pain) with resolution of or improvement in flank pain based on the patient-reported symptom assessment response at the Day 5 visit in the mMITT analysis set. The sponsor will conclude noninferiority if the lower limit of the 95% CI of difference (corresponding to a 97.5% 1-sided lower bound) is greater than -12.5% for both FDA coprimary outcome variables (symptomatic resolution at day 5 or favorable combined response at test of cure (TOC)).

  • Combined Patient-reported Symptomatic and Microbiological Response at TOC (mMITT Analysis Set): Non-inferiority Hypothesis Test [ Time Frame: At TOC visit. TOC visit is 21 to 25 days from Randomization. ] [ Designated as safety issue: No ]
    Number of patients with both a favorable per patient microbiological response and symptomatic resolution (or return to premorbid state) of all UTI-specific symptoms (frequency/urgency/dysuria/suprapubic pain/flank pain) based on the patient-reported symptom assessment response at the TOC visit in the mMITT analysis set. The sponsor will conclude noninferiority if the lower limit of the 95% CI of difference (corresponding to a 97.5% 1-sided lower bound) is greater than -12.5% for both FDA coprimary outcome variables (symptomatic resolution at day 5 or favorable combined response at test of cure (TOC)).

  • Per-patient Microbiological Response at TOC (mMITT Analysis Set): Non-inferiority Hypothesis Test [ Time Frame: At TOC visit. TOC visit is 21 to 25 days from Randomization. ] [ Designated as safety issue: No ]
    Number of patients with a favorable per patient microbiological response at TOC. The primary efficacy outcome variable for ROW is the proportion of patients with a favorable per-patient microbiological response at the TOC visit in the mMITT analysis set.


Secondary Outcome Measures:
  • Per-patient Microbiological Response at EOT (IV) (mMITT Analysis Set) [ Time Frame: At EOT (IV) visit. EOT (IV) visit is Within 24 hours after completion of the last infusion of IV study therapy and on/before the first dose for oral study therapy ] [ Designated as safety issue: No ]
    Number of patients with a favorable per-patient microbiological response at EOT (IV)

  • Per-patient Microbiological Response at LFU (mMITT Analysis Set) [ Time Frame: At LFU visit. LFU visit is 45 to 52 days from Randomization. ] [ Designated as safety issue: No ]
    Number of patients with a favorable per patient microbiological response at LFU

  • Per-patient Microbiological Response at EOT (IV) (ME at EOT (IV) Analysis Set) [ Time Frame: At EOT (IV) visit. EOT (IV) visit is Within 24 hours after completion of the last infusion of IV study therapy and on/before the first dose for oral study therapy ] [ Designated as safety issue: No ]
    Number of patients with a favorable per-patient microbiological response at EOT (IV)

  • Per-patient Microbiological Response at TOC (ME at TOC Analysis Set) [ Time Frame: At TOC visit. TOC visit is 21 to 25 days from Randomization. ] [ Designated as safety issue: No ]
    Number of patients with a favorable per patient microbiological response at TOC

  • Per-patient Microbiological Response at LFU (ME at LFU Analysis Set) [ Time Frame: At LFU visit. LFU visit is 45 to 52 days from Randomization. ] [ Designated as safety issue: No ]
    Number of patients with a favorable per patient microbiological response at LFU

  • Per-patient Microbiological Response at EOT (IV) (Extended ME at EOT (IV) Analysis Set) [ Time Frame: At EOT (IV) visit. EOT (IV) visit is Within 24 hours after completion of the last infusion of IV study therapy and on/before the first dose for oral study therapy ] [ Designated as safety issue: No ]
    Number of patients with a favorable per-patient microbiological response at EOT (IV)

  • Per-patient Microbiological Response at TOC (Extended ME at TOC Analysis Set) [ Time Frame: At TOC visit. TOC visit is 21 to 25 days from Randomization. ] [ Designated as safety issue: No ]
    Number of patients with a favorable per patient microbiological response at TOC

  • Per-patient Microbiological Response at LFU (Extended ME at LFU Analysis Set) [ Time Frame: At LFU visit. LFU visit is 45 to 52 days from Randomization. ] [ Designated as safety issue: No ]
    Number of patients with a favorable per patient microbiological response at LFU

  • Investigator Determined Clinical Response at EOT (IV) (mMITT Analysis Set) [ Time Frame: At EOT (IV) visit. EOT (IV) visit is Within 24 hours after completion of the last infusion of IV study therapy and on/before the first dose for oral study therapy ] [ Designated as safety issue: No ]
    Number of patients with a clinical cure at EOT (IV). The investigator should consider the entirety of the patient's clinical course and current status, including an evaluation of signs and symptoms (eg, fever, dysuria, costovertebral angle tenderness) and physical examination in order to classify the patient's clinical response.

  • Investigator Determined Clinical Response at TOC (mMITT Analysis Set) [ Time Frame: At TOC visit. TOC visit is 21 to 25 days from Randomization. ] [ Designated as safety issue: No ]
    Number of patients with a clinical cure at TOC. The investigator should consider the entirety of the patient's clinical course and current status, including an evaluation of signs and symptoms (eg, fever, dysuria, costovertebral angle tenderness) and physical examination in order to classify the patient's clinical response.

  • Investigator Determined Clinical Response at LFU (mMITT Analysis Set) [ Time Frame: At LFU visit. LFU visit is 45 to 52 days from Randomization. ] [ Designated as safety issue: No ]
    Number of patients with a clinical cure at LFU. The investigator should consider the entirety of the patient's clinical course and current status, including an evaluation of signs and symptoms (eg, fever, dysuria, costovertebral angle tenderness) and physical examination in order to classify the patient's clinical response.

  • Investigator Determined Clinical Response at EOT (IV) (ME at EOT (IV) Analysis Set) [ Time Frame: At EOT (IV) visit. EOT (IV) visit is Within 24 hours after completion of the last infusion of IV study therapy and on/before the first dose for oral study therapy ] [ Designated as safety issue: No ]
    Number of patients with a clinical cure at EOT (IV). The investigator should consider the entirety of the patient's clinical course and current status, including an evaluation of signs and symptoms (eg, fever, dysuria, costovertebral angle tenderness) and physical examination in order to classify the patient's clinical response.

  • Investigator Determined Clinical Response at TOC (ME at TOC Analysis Set) [ Time Frame: At TOC visit. TOC visit is 21 to 25 days from Randomization. ] [ Designated as safety issue: No ]
    Number of patients with a clinical cure at TOC. The investigator should consider the entirety of the patient's clinical course and current status, including an evaluation of signs and symptoms (eg, fever, dysuria, costovertebral angle tenderness) and physical examination in order to classify the patient's clinical response.

  • Investigator Determined Clinical Response at LFU (ME at LFU Analysis Set) [ Time Frame: At LFU visit. LFU visit is 45 to 52 days from Randomization. ] [ Designated as safety issue: No ]
    Number of patients with a clinical cure at LFU. The investigator should consider the entirety of the patient's clinical course and current status, including an evaluation of signs and symptoms (eg, fever, dysuria, costovertebral angle tenderness) and physical examination in order to classify the patient's clinical response.

  • Investigator Determined Clinical Response at EOT (IV) (Extended ME at EOT (IV) Analysis Set) [ Time Frame: At EOT (IV) visit. EOT (IV) visit is Within 24 hours after completion of the last infusion of IV study therapy and on/before the first dose for oral study therapy ] [ Designated as safety issue: No ]
    Number of patients with a clinical cure at EOT (IV). The investigator should consider the entirety of the patient's clinical course and current status, including an evaluation of signs and symptoms (eg, fever, dysuria, costovertebral angle tenderness) and physical examination in order to classify the patient's clinical response.

  • Investigator Determined Clinical Response at TOC (Extended ME at TOC Analysis Set) [ Time Frame: At TOC visit. TOC visit is 21 to 25 days from Randomization. ] [ Designated as safety issue: No ]
    Number of patients with a clinical cure at TOC. The investigator should consider the entirety of the patient's clinical course and current status, including an evaluation of signs and symptoms (eg, fever, dysuria, costovertebral angle tenderness) and physical examination in order to classify the patient's clinical response.

  • Investigator Determined Clinical Response at LFU (Extended ME at LFU Analysis Set) [ Time Frame: At LFU visit. LFU visit is 45 to 52 days from Randomization. ] [ Designated as safety issue: No ]
    Number of patients with a clinical cure at LFU. The investigator should consider the entirety of the patient's clinical course and current status, including an evaluation of signs and symptoms (eg, fever, dysuria, costovertebral angle tenderness) and physical examination in order to classify the patient's clinical response.

  • Investigator Determined Clinical Response at EOT (IV) (CE at EOT (IV) Analysis Set) [ Time Frame: At EOT (IV) visit. EOT (IV) visit is Within 24 hours after completion of the last infusion of IV study therapy and on/before the first dose for oral study therapy ] [ Designated as safety issue: No ]
    Number of patients with a clinical cure at EOT (IV). The investigator should consider the entirety of the patient's clinical course and current status, including an evaluation of signs and symptoms (eg, fever, dysuria, costovertebral angle tenderness) and physical examination in order to classify the patient's clinical response.

  • Investigator Determined Clinical Response at TOC (CE at TOC Analysis Set) [ Time Frame: At TOC visit. TOC visit is 21 to 25 days from Randomization. ] [ Designated as safety issue: No ]
    Number of patients with a clinical cure at TOC. The investigator should consider the entirety of the patient's clinical course and current status, including an evaluation of signs and symptoms (eg, fever, dysuria, costovertebral angle tenderness) and physical examination in order to classify the patient's clinical response.

  • Investigator Determined Clinical Response at LFU (CE at LFU Analysis Set) [ Time Frame: At LFU visit. LFU visit is 45 to 52 days from Randomization. ] [ Designated as safety issue: No ]
    Number of patients with a clinical cure at LFU. The investigator should consider the entirety of the patient's clinical course and current status, including an evaluation of signs and symptoms (eg, fever, dysuria, costovertebral angle tenderness) and physical examination in order to classify the patient's clinical response.

  • Investigator Determined Clinical Response at TOC for Patients Infected by Ceftazidime-resistant Gram-negative Pathogen (mMITT Analysis Set) [ Time Frame: At TOC visit. TOC visit is 21 to 25 days from Randomization. ] [ Designated as safety issue: No ]
    Clinical cure at the TOC visit for patients infected with a ceftazidime resistant pathogen in the mMITT analysis set. Includes patients infected by at least one ceftazidime-resistant Gram-negative pathogen.

  • Investigator Determined Clinical Response at TOC for Patients Infected by Ceftazidime-resistant Gram-negative Pathogen (ME at TOC Analysis Set) [ Time Frame: At TOC visit. TOC visit is 21 to 25 days from Randomization. ] [ Designated as safety issue: No ]
    Clinical cure at the TOC visit for patients infected with a ceftazidime resistant pathogen in the ME at TOC analysis set. Includes patients infected by at least one ceftazidime-resistant Gram-negative pathogen.

  • Investigator Determined Clinical Response at TOC for Patients Infected by Ceftazidime-resistant Gram-negative Pathogen (Extended ME at TOC Analysis Set) [ Time Frame: At TOC visit. TOC visit is 21 to 25 days from Randomization. ] [ Designated as safety issue: No ]
    Clinical cure at the TOC visit for patients infected with a ceftazidime resistant pathogen in the Extended ME at TOC analysis set. Includes patients infected by at least one ceftazidime-resistant Gram-negative pathogen.

  • Per-patient Microbiological Response at TOC in Patients Infected by Ceftazidime-resistant Gram-negative Pathogen (mMITT Analysis Set) [ Time Frame: At TOC visit. TOC visit is 21 to 25 days from Randomization. ] [ Designated as safety issue: No ]
    Favorable per-patient microbiological response at the TOC visit for patients infected with a ceftazidime resistant pathogen in the mMITT analysis set.

  • Per-patient Microbiological Response at TOC in Patients Infected by Ceftazidime-resistant Gram-negative Pathogen (ME at TOC Analysis Set) [ Time Frame: At TOC visit. TOC visit is 21 to 25 days from Randomization. ] [ Designated as safety issue: No ]
    Favorable per-patient microbiological response at the TOC visit for patients infected with a ceftazidime resistant pathogen in the ME at TOC analysis set.

  • Per-patient Microbiological Response at TOC in Patients Infected by Ceftazidime-resistant Gram-negative Pathogen (Extended ME at TOC Analysis Set) [ Time Frame: At TOC visit. TOC visit is 21 to 25 days from Randomization. ] [ Designated as safety issue: No ]
    Favorable per-patient microbiological response at the TOC visit for patients infected with a ceftazidime resistant pathogen in the Extended ME at TOC analysis set.

  • Time to First Defervescence While on IV Study Therapy (mMITT Analysis Set) [ Time Frame: Time to first defervescence is defined as the time (in days) from the first dose of IV study therapy to first absence of fever, which is temperature ≤ 37.8 C in a 24-hour period. ] [ Designated as safety issue: No ]
    Time to first defervescence while on IV study therapy in patients in the mMITT analysis set who have fever at study entry.

  • Time to First Defervescence While on IV Study Therapy (ME at TOC Analysis Set) [ Time Frame: Time to first defervescence is defined as the time (in days) from the first dose of IV study therapy to first absence of fever, which is temperature ≤ 37.8 C in a 24-hour period. ] [ Designated as safety issue: No ]
    Time to first defervescence while on IV study therapy in patients in the ME at TOC analysis set who have fever at study entry.

  • Time to First Defervescence While on IV Study Therapy (Extended ME at TOC Analysis Set) [ Time Frame: Time to first defervescence is defined as the time (in days) from the first dose of IV study therapy to first absence of fever, which is temperature ≤ 37.8 C in a 24-hour period. ] [ Designated as safety issue: No ]
    Time to first defervescence while on IV study therapy in patients in the Extended ME at TOC analysis set who have fever at study entry.

  • Time to First Defervescence While on IV Study Therapy (CE at TOC Analysis Set) [ Time Frame: Time to first defervescence is defined as the time (in days) from the first dose of IV study therapy to first absence of fever, which is temperature ≤ 37.8 C in a 24-hour period. ] [ Designated as safety issue: No ]
    Time to first defervescence while on IV study therapy in patients in the CE at TOC analysis set who have fever at study entry.

  • Per-pathogen Microbiological Response at EOT (IV) for Baseline Pathogen (mMITT Analysis Set) [ Time Frame: At EOT IV visit. EOT (IV) visit is Within 24 hours after completion of the last infusion of IV study therapy and on/before the first dose for oral study therapy ] [ Designated as safety issue: No ]
    Number of favorable per-pathogen microbiological responses at the EOT (IV) visit in the mMITT analysis set

  • Per-pathogen Microbiological Response at TOC for Baseline Pathogen (mMITT Analysis Set) [ Time Frame: At TOC visit. TOC visit is 21 to 25 days from Randomization ] [ Designated as safety issue: No ]
    Number of favorable per-pathogen microbiological responses at the TOC visit in the mMITT analysis set

  • Per-pathogen Microbiological Response at LFU for Baseline Pathogen (mMITT Analysis Set) [ Time Frame: At LFU visit. LFU visit is 45 to 52 days from Randomization ] [ Designated as safety issue: No ]
    Number of favorable per-pathogen microbiological responses at the LFU visit in the mMITT analysis set

  • Per-pathogen Microbiological Response at EOT (IV) for Baseline Pathogen (Extended ME at EOT (IV) Analysis Set) [ Time Frame: At EOT IV visit. EOT (IV) visit is Within 24 hours after completion of the last infusion of IV study therapy and on/before the first dose for oral study therapy ] [ Designated as safety issue: No ]
    Number of favorable per-pathogen microbiological responses at the EOT (IV) visit in the Extended ME at EOT (IV) analysis set

  • Per-pathogen Microbiological Response at TOC for Baseline Pathogen (Extended ME at TOC Analysis Set) [ Time Frame: At TOC visit. TOC visit is 21 to 25 days from Randomization. ] [ Designated as safety issue: No ]
    Number of favorable per-pathogen microbiological responses at the TOC visit in the Extended ME at TOC analysis set

  • Per-pathogen Microbiological Response at LFU for Baseline Pathogen (Extended ME at LFU Analysis Set) [ Time Frame: At LFU visit. LFU visit is 45 to 52 days from Randomization. ] [ Designated as safety issue: No ]
    Number of favorable per-pathogen microbiological responses at the LFU visit in the Extended ME at LFU analysis set

  • Per-pathogen Microbiological Response at EOT (IV) for Baseline Pathogen (ME at EOT (IV) Analysis Set) [ Time Frame: At EOT (IV) visit. EOT (IV) visit is Within 24 hours after completion of the last infusion of IV study therapy and on/before the first dose for oral study therapy ] [ Designated as safety issue: No ]
    Number of favorable per-pathogen microbiological responses at the EOT (IV) visit in the ME at EOT (IV) analysis set

  • Per-pathogen Microbiological Response at TOC for Baseline Pathogen (ME at TOC Analysis Set) [ Time Frame: At TOC visit. TOC visit is 21 to 25 days from Randomization. ] [ Designated as safety issue: No ]
    Number of favorable per-pathogen microbiological responses at the TOC visit in the ME at TOC analysis set

  • Per-pathogen Microbiological Response at LFU for Baseline Pathogen (ME at LFU Analysis Set) [ Time Frame: At LFU visit. LFU visit is 45 to 52 days from Randomization. ] [ Designated as safety issue: No ]
    Number of favorable per-pathogen microbiological responses at the LFU visit in the ME at LFU analysis set

  • Per-pathogen Microbiological Response at EOT (IV) for Blood Only (mMITT Analysis Set) [ Time Frame: At EOT IV visit. EOT (IV) visit is Within 24 hours after completion of the last infusion of IV study therapy and on/before the first dose for oral study therapy ] [ Designated as safety issue: No ]
    Number of favorable per-pathogen microbiological responses at the EOT (IV) visit in the mMITT analysis set for blood only

  • Per-pathogen Microbiological Response at TOC for Blood Only (mMITT Analysis Set) [ Time Frame: At TOC visit. TOC visit is 21 to 25 days from Randomization ] [ Designated as safety issue: No ]
    Number of favorable per-pathogen microbiological responses at the TOC visit in the mMITT analysis set for blood only

  • Per-pathogen Microbiological Response at LFU for Blood Only (mMITT Analysis Set) [ Time Frame: At LFU visit. LFU visit is 45 to 52 days from Randomization ] [ Designated as safety issue: No ]
    Number of favorable per-pathogen microbiological responses at the LFU visit in the mMITT analysis set for blood only

  • Per-pathogen Microbiological Response at EOT (IV) for Blood Only (Extended ME at EOT (IV) Analysis Set) [ Time Frame: At EOT IV visit. EOT (IV) visit is Within 24 hours after completion of the last infusion of IV study therapy and on/before the first dose for oral study therapy ] [ Designated as safety issue: No ]
    Number of favorable per-pathogen microbiological responses at the EOT (IV) visit in the Extended ME at EOT (IV) analysis set for blood only

  • Per-pathogen Microbiological Response at TOC for Blood Only (Extended ME at TOC Analysis Set) [ Time Frame: At TOC visit. TOC visit is 21 to 25 days from Randomization. ] [ Designated as safety issue: No ]
    Number of favorable per-pathogen microbiological responses at the TOC visit in the Extended ME at TOC analysis set for blood only

  • Per-pathogen Microbiological Response at LFU for Blood Only (Extended ME at LFU Analysis Set) [ Time Frame: At LFU visit. LFU visit is 45 to 52 days from Randomization. ] [ Designated as safety issue: No ]
    Number of favorable per-pathogen microbiological responses at the LFU visit in the Extended ME at LFU analysis set for blood only

  • Per-pathogen Microbiological Response at EOT (IV) for Blood Only (ME at EOT (IV) Analysis Set) [ Time Frame: At EOT (IV) visit. EOT (IV) visit is Within 24 hours after completion of the last infusion of IV study therapy and on/before the first dose for oral study therapy ] [ Designated as safety issue: No ]
    Number of favorable per-pathogen microbiological responses at the EOT (IV) visit in the ME at EOT (IV) analysis set for blood only

  • Per-pathogen Microbiological Response at TOC for Blood Only (ME at TOC Analysis Set) [ Time Frame: At TOC visit. TOC visit is 21 to 25 days from Randomization. ] [ Designated as safety issue: No ]
    Number of favorable per-pathogen microbiological responses at the TOC visit in the ME at TOC analysis set for blood only

  • Per-pathogen Microbiological Response at LFU for Blood Only (ME at LFU Analysis Set) [ Time Frame: At LFU visit. LFU visit is 45 to 52 days from Randomization. ] [ Designated as safety issue: No ]
    Number of favorable per-pathogen microbiological responses at the LFU visit in the ME at LFU analysis set for blood only

  • Per-pathogen Microbiological Response at TOC by CAZ AVI MIC for Baseline Pathogen (mMITT Analysis Set) [ Time Frame: At TOC visit. TOC visit is 21 to 25 days from Randomization ] [ Designated as safety issue: No ]
    Per pathogen microbiological response at TOC by CAZ-AVI MIC for baseline pathogen in the mMITT analysis set

  • Per-pathogen Microbiological Response at TOC by CAZ AVI MIC for Baseline Pathogen (Extended ME at TOC Analysis Set) [ Time Frame: At TOC visit. TOC visit is 21 to 25 days from Randomization ] [ Designated as safety issue: No ]
    Per pathogen microbiological response at TOC by CAZ-AVI MIC for baseline pathogen in the Extended ME at TOC analysis set

  • Per-pathogen Microbiological Response at TOC by CAZ AVI MIC for Baseline Pathogen (ME at TOC Analysis Set) [ Time Frame: At TOC visit. TOC visit is 21 to 25 days from Randomization ] [ Designated as safety issue: No ]
    Per pathogen microbiological response at TOC by CAZ-AVI MIC for baseline pathogen in the ME at TOC analysis set

  • Per-pathogen Microbiological Response at TOC by Doripenem MIC for Baseline Pathogen (mMITT Analysis Set) [ Time Frame: At TOC visit. TOC visit is 21 to 25 days from Randomization ] [ Designated as safety issue: No ]
    Per pathogen microbiological response at TOC by Doripenem MIC for baseline pathogen in the mMITT analysis set

  • Per-pathogen Microbiological Response at TOC by Doripenem MIC for Baseline Pathogen (Extended ME at TOC Analysis Set) [ Time Frame: At TOC visit. TOC visit is 21 to 25 days from Randomization ] [ Designated as safety issue: No ]
    Per pathogen microbiological response at TOC by Doripenem MIC for baseline pathogen in the Extended ME at TOC analysis set

  • Per-pathogen Microbiological Response at TOC by Doripenem MIC for Baseline Pathogen (ME at TOC Analysis Set) [ Time Frame: At TOC visit. TOC visit is 21 to 25 days from Randomization ] [ Designated as safety issue: No ]
    Per pathogen microbiological response at TOC by Doripenem MIC for baseline pathogen in the ME at TOC analysis set

  • Plasma Concentrations for Ceftazidime Within 15 Minutes Before/After Dose (PK Analysis Set) [ Time Frame: within 15 minutes before/after dose ] [ Designated as safety issue: No ]
    Blood samples were taken on Day 3 for ceftazidime (CAZ) and avibactam (AVI) plasma concentration.

  • Plasma Concentrations for Ceftazidime Between 30 to 90 Minutes After Dose(PK Analysis Set) [ Time Frame: Between 30 to 90 minutes after dose ] [ Designated as safety issue: No ]
    Blood samples were taken on Day 3 for ceftazidime (CAZ) and avibactam (AVI) plasma concentration.

  • Plasma Concentrations for Ceftazidime Between 300 to 360 Minutes After Dose(PK Analysis Set) [ Time Frame: Between 300 to 360 minutes after dose ] [ Designated as safety issue: No ]
    Blood samples were taken on Day 3 for ceftazidime (CAZ) and avibactam (AVI) plasma concentration.

  • Plasma Concentrations for Avibactam Within 15 Minutes Before/After Dose (PK Analysis Set) [ Time Frame: within 15 minutes before/after dose ] [ Designated as safety issue: No ]
    Blood samples were taken on Day 3 for ceftazidime (CAZ) and avibactam (AVI) plasma concentration.

  • Plasma Concentrations for Avibactam Between 30 to 90 Minutes After Dose(PK Analysis Set) [ Time Frame: Between 30 to 90 minutes after dose ] [ Designated as safety issue: No ]
    Blood samples were taken on Day 3 for ceftazidime (CAZ) and avibactam (AVI) plasma concentration.

  • Plasma Concentrations for Avibactam Between 300 to 360 Minutes After Dose(PK Analysis Set) [ Time Frame: Between 300 to 360 minutes after dose ] [ Designated as safety issue: No ]
    Blood samples were taken on Day 3 for ceftazidime (CAZ) and avibactam (AVI) plasma concentration.


Enrollment: 641
Study Start Date: October 2012
Study Completion Date: August 2014
Primary Completion Date: August 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: Either switch to oral therapy: 500 mg of Ciprofloxacin (oral)
Patients are eligible for oral switch after receiving 5 full days of IV therapy and have met protocol specified criteria for clinical improvement
Drug: or switch to oral therapy: 800 mg/160 mg of sulfamethoxazole/trimethoprim (oral)
Patients are eligible for oral switch after receiving 5 full days of IV therapy and have met protocol specified criteria for clinical improvement
Active Comparator: Doripenem
IV treatment
Drug: Doripenem
500 mg of Doripenem. Patients randomized to receive Doripenem will receive an infusion of Doripenem 500 mg every 8 hours administered by intravenous (IV) infusion in a volume of 100 mL at a constant rate over 60 minutes
Drug: Either switch to oral therapy: 500 mg of Ciprofloxacin (oral)
Patients are eligible for oral switch after receiving 5 full days of IV therapy and have met protocol specified criteria for clinical improvement
Drug: or switch to oral therapy: 800 mg/160 mg of sulfamethoxazole/trimethoprim (oral)
Patients are eligible for oral switch after receiving 5 full days of IV therapy and have met protocol specified criteria for clinical improvement

Detailed Description:
A Phase III, Randomized, Multicenter, Double-Blind, Double Dummy, Parallel Group, Comparative Study to Determine the Efficacy, Safety, and Tolerability of Ceftazidime Avibactam (CAZ-AVI, formerly CAZ104) Versus Doripenem Followed by Appropriate Oral Therapy in the Treatment of Complicated Urinary Tract Infections, Including Acute Pyelonephritis, With a Gram Negative Pathogen in Hospitalized Adults
  Eligibility

Ages Eligible for Study:   18 Years to 90 Years   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 18 to 90 years of age inclusive
  • 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
  • Has pyuria with >/= 10 WBCs (white blood cell) and has a positive urine culture within 48 hours of enrollment containing >/=10 to the fifth CFU (colony forming unit ) /ml of a recognized uropathogen known to be susceptible to IV study therapy (CAZ-AVI and doripenem)
  • Demonstrates either acute pyelonephritis or complicated lower UTI without pyelonephritis

Exclusion Criteria:

  • Urine pathogen is a Gram-positive pathogen or a uropathogen resistant to CAZ-AVI or doripenem
  • Patient's urine culture at study entry isolates more than 2 microorganisms regardless of colony count or patient has a confirmed fungal UTI
  • Patient is receiving hemodialysis or peritoneal dialysis or had a renal transplant
  • Patient is immunocompromised
  • Patient is considered unlikely to survive the 6- to 8-week study period or has a rapidly progressive or terminal illness including septic shock which is associated with a high risk of mortality
  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: NCT01599806

  Show 60 Study Locations
Sponsors and Collaborators
AstraZeneca
Forest Laboratories
Investigators
Study Director: Paul Newell, MBBS, MRCP AstraZeneca
  More Information

Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT01599806     History of Changes
Other Study ID Numbers: D4280C00004  2011-005722-21 
Study First Received: May 15, 2012
Results First Received: November 4, 2015
Last Updated: February 3, 2016
Health Authority: Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
Brazil: National Health Surveillance Agency
Bulgaria: Bulgarian Drug Agency
Canada: Health Canada
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
Israel: Ministry of Health
India: Drugs Controller General of India
Italy: National Institute of Health
Mexico: Federal Commission for Sanitary Risks Protection
Peru: Ministry of Health
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 Korea: Korea Food and Drug Administration (KFDA)
Spain: Spanish Agency of Medicines
Taiwan : Food and Drug Administration
Ukraine: State Pharmacological Center - Ministry of Health
United States: Food and Drug Administration

Keywords provided by AstraZeneca:
Ceftazidime, Avibactam, Doripenem, Ciprofloxacin, sulfamethoxazole/trimethoprim, Anti-Infective Agents, Complicated Urinary Tract Infection,Acute Pyelonephritis

Additional relevant MeSH terms:
Infection
Communicable Diseases
Urinary Tract Infections
Pyelonephritis
Urologic Diseases
Nephritis, Interstitial
Nephritis
Kidney Diseases
Pyelitis
Ciprofloxacin
Ceftazidime
Avibactam
Avibactam, ceftazidime drug combination
Trimethoprim, Sulfamethoxazole Drug Combination
Sulfamethoxazole
Trimethoprim
Anti-Bacterial Agents
Anti-Infective Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Cytochrome P-450 CYP1A2 Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Anti-Infective Agents, Urinary
Renal Agents
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents

ClinicalTrials.gov processed this record on September 27, 2016