A Study Comparing Ceftazidime-Avibactam Versus Meropenem in Hospitalized Adults With Nosocomial Pneumonia

A Phase III, Randomized, Multicentre, Double-blind, Double-dummy, Parallel-group Comparative Study to Determine the Efficacy, Safety And Tolerability of Ceftazidime-Avibactam Versus Meropenem in the Treatment of Nosocomial Pneumonia Including Ventilator-Associated Pneumonia in Hospitalized Adults

The purpose of the study is to evaluate the effects of Ceftazidime-Avibactam compared to Meropenem for treating hospitalized adults with nosocomial pneumonia including ventilator-associated pneumonia

Study Overview

• Status: Completed
• Conditions: Ventilator-associated Pneumonia (VAP); Nosocomial Pneumonia (NP)
• Intervention / Treatment: Drug: ceftazidim-avibactam (CAZ-AVI, experimental product); Drug: meropenem (active comparator)

Detailed Description

A Phase III, Randomized, Multicentre, Double-blind, Double-dummy, Parallel-group Comparative Study to Determine the Efficacy, Safety And Tolerability of Ceftazidime-Avibactam Versus Meropenem in the Treatment of Nosocomial Pneumonia Including Ventilator-Associated Pneumonia in Hospitalized Adults

• Study Type: Interventional
• Enrollment (Actual): 969
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina
    • Research Site
  • Cordoba, Argentina
    • Research Site
  • Florida, Argentina
    • Research Site
  • La Plata, Argentina
    • Research Site
  • Mendoza, Argentina
    • Research Site
• Brazil
  • Belo Horizonte, Brazil
    • Research Site
  • Campinas/SP, Brazil
    • Research Site
  • Curitiba, Brazil
    • Research Site
  • São José do Rio Preto, Brazil
    • Research Site
• Bulgaria
  • Burgas, Bulgaria
    • Research Site
  • Plovdiv, Bulgaria
    • Research Site
  • Ruse, Bulgaria
    • Research Site
  • Sofia, Bulgaria
    • Research Site
• China
  • Beijing, China
    • Research Site
  • Changsha, China
    • Research Site
  • Chengdu, China
    • Research Site
  • Chongqing, China
    • Research Site
  • Guangzhou, China
    • Research Site
  • Haikou, China
    • Research Site
  • Hangzhou, China
    • Research Site
  • Jiangyin, China
    • Research Site
  • Nanchang, China
    • Research Site
  • Qingdao, China
    • Research Site
  • Sanya, China
    • Research Site
  • Shanghai, China
    • Research Site
  • Shenyang, China
    • Research Site
  • Shenzhen, China
    • Research Site
  • Suzhou, China
    • Research Site
  • Tianjin, China
    • Research Site
  • Xi'an, China
    • Research Site
  • Xiamen, China
    • Research Site
  • Yangzhou, China
    • Research Site
  • Zhanjiang, China
    • Research Site
• Czechia
  • Kolin, Czechia
    • Research Site
  • Kyjov, Czechia
    • Research Site
  • Praha 10, Prague, Czechia
    • Research Site
• France
  • Limoges, France
    • Research Site
  • Nantes Cedex 1, France
    • Research Site
  • Paris 14, France
    • Research Site
  • Paris Cedex, France
    • Research Site
  • Pierre Benite Cedex, France
    • Research Site
  • Poitiers Cedex, France
    • Research Site
  • Strasbourg Cedex, France
    • Research Site
  • Tours, France
    • Research Site
• Hungary
  • Budapest, Hungary
    • Research Site
  • Miskolc, Hungary
    • Research Site
  • Székesfehérvár, Hungary
    • Research Site
  • Veszprém, Hungary
    • Research Site
• India
  • Bangalore, India
    • Research Site
  • Jaipur, India
    • Research Site
  • Lucknow, India
    • Research Site
  • Pune, India
    • Research Site
  • Varanasi, India
    • Research Site
• Italy
  • Bologna, Italy
    • Research Site
• Japan
  • Fukuoka-shi, Japan
    • Research Site
  • Higashiibaraki-gun, Japan
    • Research Site
  • Ikeda-shi, Japan
    • Research Site
  • Itabashi-ku, Japan
    • Research Site
  • Izumo-shi, Japan
    • Research Site
  • Kagoshima-shi, Japan
    • Research Site
  • Kawasaki-shi, Japan
    • Research Site
  • Kitakyushu-shi, Japan
    • Research Site
  • Kushiro-shi, Japan
    • Research Site
  • Matsuyama-shi, Japan
    • Research Site
  • Osaka-shi, Japan
    • Research Site
  • Saga-shi, Japan
    • Research Site
  • Sapporo-shi, Japan
    • Research Site
  • Sasebo-shi, Japan
    • Research Site
  • Tsuchiura-shi, Japan
    • Research Site
  • Tsukubo-gun, Japan
    • Research Site
  • Uji-shi, Japan
    • Research Site
  • Uki-shi, Japan
    • Research Site
  • Yanai-shi, Japan
    • Research Site
• Korea, Republic of
  • Ansan-si, Korea, Republic of
    • Research Site
  • Anyang-si, Korea, Republic of
    • Research Site
  • Incheon, Korea, Republic of
    • Research Site
  • Jinju-si, Korea, Republic of
    • Research Site
  • Seoul, Korea, Republic of
    • Research Site
  • Wonju-si, Korea, Republic of
    • Research Site
• Latvia
  • Liepaja, Latvia
    • Research Site
• Mexico
  • Guadalajara, Mexico
    • Research Site
  • Monterrey, Mexico
    • Research Site
• Peru
  • Cusco, Peru
    • Research Site
  • Lima, Peru
    • Research Site
• Philippines
  • Iloilo City, Philippines
    • Research Site
  • Quezon City, Philippines
    • Research Site
• Poland
  • Bydgoszcz, Poland
    • Research Site
  • Chrzanów, Poland
    • Research Site
  • Lublin, Poland
    • Research Site
  • Olsztyn, Poland
    • Research Site
  • Proszowice, Poland
    • Research Site
  • Suwałki, Poland
    • Research Site
  • Łęczna, Poland
    • Research Site
• Romania
  • Craiova, Romania
    • Research Site
  • Timisoara, Romania
    • Research Site
• Russian Federation
  • Arkhangelsk, Russian Federation
    • Research Site
  • Chelyabinsk, Russian Federation
    • Research Site
  • Moscow, Russian Federation
    • Research Site
  • Saint Petersburg, Russian Federation
    • Research Site
  • Smolensk, Russian Federation
    • Research Site
  • St. Petersburg, Russian Federation
    • Research Site
  • Zelenograd, Russian Federation
    • Research Site
• Slovenia
  • Golnik, Slovenia
    • Research Site
• South Africa
  • Randburg, South Africa
    • Research Site
• Spain
  • Barcelona, Spain
    • Research Site
  • Madrid, Spain
    • Research Site
  • Sabadell(Barcelona), Spain
    • Research Site
  • Terrassa (Barcelona), Spain
    • Research Site
• Taiwan
  • Taichung, Taiwan
    • Research Site
• Turkey
  • Ankara, Turkey
    • Research Site
• Ukraine
  • Dnipropetrovsk, Ukraine
    • Research Site
  • Donetsk, Ukraine
    • Research Site
  • Ivano-Frankivsk, Ukraine
    • Research Site
  • Kharkiv, Ukraine
    • Research Site
  • Kyiv, Ukraine
    • Research Site
  • Mykolayiv, Ukraine
    • Research Site
  • Poltava, Ukraine
    • Research Site
  • Vinnytsia, Ukraine
    • Research Site
• United Kingdom
  • Birmingham, United Kingdom
    • Research Site
  • Blackpool, United Kingdom
    • Research Site
  • Guildford, United Kingdom
    • Research Site
  • Hull, United Kingdom
    • Research Site
• Vietnam
  • Hanoi, Vietnam
    • Research Site
  • Ho Chi Minh, Vietnam
    • Research Site
  • Hochiminh, Vietnam
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 18 to 90 years of age inclusive
• Females can participate if surgically sterile or completed menopause; if able to have children, must have negative serum pregnancy test, agree not to attempt pregnancy and use acceptable contraception while receiving study therapy and for 1 week after
• Onset of symptoms ≥ 48 hours after admission or <7 days after discharge from an inpatient acute or chronic care facility
• New or worsening infiltrate on chest X-ray obtained within 48 hours prior to randomization
• At least 1 of the following systemic signs:Fever (temperature >38 C) or hypothermia (rectal/core temperature <35 C); White blood cell count >10,000 cells/mm3, or White blood cell count <4500 cells/mm3, or >15% band forms.

Exclusion Criteria:

• Pulmonary disease that, in the investigator's judgment, would preclude evaluation of therapeutic response (e.g. lung cancer, active tuberculosis, cystic fibrosis, granulomatous disease, fungal pulmonary infection or recent pulmonary embolism).
• Patients with lung abscess, pleural empyema or post obstructive pneumonia.
• Patients with an estimated creatinine clearance <16ml/min by Cockcroft Gault formula or patients expected to require haemodialysis or other renal support while on study therapy.
• Acute hepatitis in the prior 6 months, cirrhosis, acute hepatic failure or acute decompensation of chronic hepatic failure.
• Patients receiving hemodialysis or peritoneal dialysis.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: CAZ-AVI; Intra-Venous treatment	Drug: ceftazidim-avibactam (CAZ-AVI, experimental product); 2000mg ceftazidime plus 500mg avibactam
ACTIVE_COMPARATOR: Meropenem; Intra-Venous treatment	Drug: meropenem (active comparator); 1000mg of Meropenem

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Number of Patients With Clinical Cure at Test-of-cure (TOC) Visit in the Clinically Modified Intent-to-treat Analysis Set (Co-primary Analyses)	The number of patients meeting the cure criteria: the patient was not a clinical failure at end of treatment and the patient is alive and all signs and symptoms of pneumonia have resolved or improved to an extent that no antibacterial therapy for Nosocomial Pneumonia was taken between end of treatment and test-of-cure inclusive.	At the test-of-cure (TOC) visit (Day 21 to 25)
The Number of Patients With Clinical Cure at Test-of-cure (TOC) Visit in the Clinically Evaluable at TOC Analysis Set (Co-primary Analyses)	The number of patients meeting the cure criteria: the patient was not a clinical failure at end of treatment and the patient is alive and all signs and symptoms of pneumonia have resolved or improved to an extent that no antibacterial therapy for Nosocomial Pneumonia was taken between end of treatment and test-of-cure inclusive.	At the test-of-cure (TOC) visit (Day 21 to 25)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Number of Patients With Clinical Cure at Test-of-cure (TOC) Visit in the Microbiologically Modified Intent-to-treat Analysis Set	The number of patients meeting the cure criteria: the patient was not a clinical failure at end of treatment and the patient is alive and all signs and symptoms of pneumonia have resolved or improved to an extent that no antibacterial therapy for Nosocomial Pneumonia was taken between end of treatment and test-of-cure inclusive.	At the test-of-cure (TOC) visit (Day 21 to 25)
The Number of Patients With Clinical Cure at Test-of-cure (TOC) Visit in the Extended Microbiologically Evaluable Analysis Set	The number of patients meeting the cure criteria: the patient was not a clinical failure at end of treatment and the patient is alive and all signs and symptoms of pneumonia have resolved or improved to an extent that no antibacterial therapy for Nosocomial Pneumonia was taken between end of treatment and test-of-cure inclusive.	At the test-of-cure (TOC) visit (Day 21 to 25)
The Number of Patients With Clinical Cure at Test-of-cure (TOC) Visit in the Microbiologically Evaluable Analysis Set	The number of patients meeting the cure criteria: the patient was not a clinical failure at end of treatment and the patient is alive and all signs and symptoms of pneumonia have resolved or improved to an extent that no antibacterial therapy for Nosocomial Pneumonia was taken between end of treatment and test-of-cure inclusive.	At the test-of-cure (TOC) visit (Day 21 to 25)
The Number of Patients With Clinical Cure at End of Treatment (EOT) Visit in Microbiologically Modified Intent-to-treat Analysis Set	The number of patients meeting the cure criteria: the patient is alive and all signs and symptoms of pneumonia have resolved or improved such that all antibacterial therapies for Nosocomial Pneumonia are stopped. No antibacterial therapy other than those outlined by the protocol has been administered for Nosocomial Pneumonia prior to end of treatment.	Patients were followed after the last IV dose but no later than 24 hours after the last IV dose.
The Number of Patients With Clinical Cure at End of Treatment (EOT) Visit in Clinically Modified Intent-to-treat Analysis Set	The number of patients meeting the cure criteria: the patient is alive and all signs and symptoms of pneumonia have resolved or improved such that all antibacterial therapies for Nosocomial Pneumonia are stopped. No antibacterial therapy other than those outlined by the protocol has been administered for Nosocomial Pneumonia prior to end of treatment.	Patients were followed after the last IV dose but no later than 24 hours after the last IV dose.
The Number of Patients With Clinical Cure at End of Treatment (EOT) Visit in Clinically Evaluable Analysis Set	The number of patients meeting the cure criteria: the patient is alive and all signs and symptoms of pneumonia have resolved or improved such that all antibacterial therapies for Nosocomial Pneumonia are stopped. No antibacterial therapy other than those outlined by the protocol has been administered for Nosocomial Pneumonia prior to end of treatment.	Patients were followed after the last IV dose but no later than 24 hours after the last IV dose.
The Number of Patients With Clinical Cure at End of Treatment (EOT) Visit in Extended Microbiologically Evaluable Analysis Set	The number of patients meeting the cure criteria: the patient is alive and all signs and symptoms of pneumonia have resolved or improved such that all antibacterial therapies for Nosocomial Pneumonia are stopped. No antibacterial therapy other than those outlined by the protocol has been administered for Nosocomial Pneumonia prior to end of treatment.	Patients were followed after the last IV dose but no later than 24 hours after the last IV dose.
The Number of Patients With Clinical Cure at End of Treatment (EOT) Visit in Microbiologically Evaluable Analysis Set	The number of patients meeting the cure criteria: the patient is alive and all signs and symptoms of pneumonia have resolved or improved such that all antibacterial therapies for Nosocomial Pneumonia are stopped. No antibacterial therapy other than those outlined by the protocol has been administered for Nosocomial Pneumonia prior to end of treatment.	Patients were followed after the last IV dose but no later than 24 hours after the last IV dose.
The Number of Patients With a Favorable Per-patient Microbiologic Response at End of Treatment (EOT) Visit in Microbiologically Modified Intent-to-treat Analysis Set	Per-patient "favorable" response indicates that all of the patient's baseline pathogens are "eradicated" or "presumed eradicated". Eradication is defined as: source specimen demonstrates absence of the original baseline pathogen. Presumed eradication is defined as: source specimen was not available to culture and the patient was assessed as a clinical cure.	Patients were followed after the last IV dose but no later than 24 hours after the last IV dose.
The Number of Patients With a Favorable Per-patient Microbiologic Response at Test-of-cure (TOC) Visit in Microbiologically Modified Intent-to-treat Analysis Set	Per-patient "favorable" response indicates that all of the patient's baseline pathogens are "eradicated" or "presumed eradicated". Eradication is defined as: source specimen demonstrates absence of the original baseline pathogen. Presumed eradication is defined as: source specimen was not available to culture and the patient was assessed as a clinical cure.	At the test-of-cure (TOC) visit (Day 21 to 25)
The Number of Patients With a Favorable Per-patient Microbiologic Response at End of Treatment (EOT) Visit in Extended Microbiologically Evaluable at End of Treatment Analysis Set	Per-patient "favorable" response indicates that all of the patient's baseline pathogens are "eradicated" or "presumed eradicated". Eradication is defined as: source specimen demonstrates absence of the original baseline pathogen. Presumed eradication is defined as: source specimen was not available to culture and the patient was assessed as a clinical cure.	Patients were followed after the last IV dose but no later than 24 hours after the last IV dose.
The Number of Patients With a Favorable Per-patient Microbiologic Response at Test-of-cure (TOC) Visit in Extended Microbiologically Evaluable at Test-of-cure Analysis Set	Per-patient "favorable" response indicates that all of the patient's baseline pathogens are "eradicated" or "presumed eradicated". Eradication is defined as: source specimen demonstrates absence of the original baseline pathogen. Presumed eradication is defined as: source specimen was not available to culture and the patient was assessed as a clinical cure.	At the test-of-cure (TOC) visit (Day 21 to 25)
The Number of Patients With a Favorable Per-patient Microbiologic Response at End of Treatment (EOT) Visit in Microbiologically Evaluable at End of Treatment Analysis Set	Per-patient "favorable" response indicates that all of the patient's baseline pathogens are "eradicated" or "presumed eradicated". Eradication is defined as: source specimen demonstrates absence of the original baseline pathogen. Presumed eradication is defined as: source specimen was not available to culture and the patient was assessed as a clinical cure.	Patients were followed after the last IV dose but no later than 24 hours after the last IV dose.
The Number of Patients With a Favorable Per-patient Microbiologic Response at Test-of-cure (TOC) Visit in Microbiologically Evaluable at Test-of-cure Analysis Set	Per-patient "favorable" response indicates that all of the patient's baseline pathogens are "eradicated" or "presumed eradicated". Eradication is defined as: source specimen demonstrates absence of the original baseline pathogen. Presumed eradication is defined as: source specimen was not available to culture and the patient was assessed as a clinical cure.	At the test-of-cure (TOC) visit (Day 21 to 25)
The Number of Favorable Per-pathogen Microbiologic Responses at End of Treatment (EOT) Visit in Microbiologically Modified Intent-to-treat Analysis Set at End of Treatment Visit	The number of patients with a favorable per-pathogen microbiological response: favorable microbiological response includes: Eradication where, source specimen demonstrates absence of the original baseline pathogen. Presumed eradication where, source specimen was not available to culture and the patient was assessed as a clinical cure.	Patients were followed after the last IV dose but no later than 24 hours after the last IV dose.
The Number of Favorable Per-pathogen Microbiologic Responses at End of Treatment (EOT) Visit in Extended Microbiologically Evaluable at End of Treatment Analysis Set	The number of patients with a favorable per-pathogen microbiological response: favorable microbiological response includes: Eradication where, source specimen demonstrates absence of the original baseline pathogen. Presumed eradication where, source specimen was not available to culture and the patient was assessed as a clinical cure.	Patients were followed after the last IV dose but no later than 24 hours after the last IV dose.
The Number of Favorable Per-pathogen Microbiologic Responses at End of Treatment (EOT) Visit in Microbiologically Evaluable at End of Treatment Analysis Set	The number of patients with a favorable per-pathogen microbiological response: favorable microbiological response includes: Eradication where, source specimen demonstrates absence of the original baseline pathogen. Presumed eradication where, source specimen was not available to culture and the patient was assessed as a clinical cure.	Patients were followed after the last IV dose but no later than 24 hours after the last IV dose.
The Number of Favorable Per-pathogen Microbiologic Responses at Test-of-cure (TOC) Visit in Microbiologically Modified Intent-to-treat Analysis Set at Test-of-cure Visit	The number of patients with a favorable per-pathogen microbiological response: favorable microbiological response includes: Eradication where, source specimen demonstrates absence of the original baseline pathogen. Presumed eradication where, source specimen was not available to culture and the patient was assessed as a clinical cure.	At the test-of-cure (TOC) visit (Day 21 to 25)
The Number of Favorable Per-pathogen Microbiologic Responses at Test-of-cure (TOC) Visit in Extended Microbiologically Evaluable at Test-of-cure Analysis Set	The number of patients with a favorable per-pathogen microbiological response: favorable microbiological response includes: Eradication where, source specimen demonstrates absence of the original baseline pathogen. Presumed eradication where, source specimen was not available to culture and the patient was assessed as a clinical cure.	At the test-of-cure (TOC) visit (Day 21 to 25)
The Number of Favorable Per-pathogen Microbiologic Responses at Test-of-cure (TOC) Visit in Microbiologically Evaluable at Test-of-cure Analysis Set	The number of patients with a favorable per-pathogen microbiological response: favorable microbiological response includes: Eradication where, source specimen demonstrates absence of the original baseline pathogen. Presumed eradication where, source specimen was not available to culture and the patient was assessed as a clinical cure.	At the test-of-cure (TOC) visit (Day 21 to 25)
The Number of Patients With Clinical Cure in Patients With Pathogens Resistant to Ceftazidime at End of Treatment (EOT) Visit in Clinically Modified Intent-to-treat Analysis Set at End of Treatment Visit	The number of patients meeting the cure criteria: the patient is alive and all signs and symptoms of pneumonia have resolved or improved such that all antibacterial therapies for Nosocomial Pneumonia are stopped. No antibacterial therapy other than those outlined by the protocol has been administered for Nosocomial Pneumonia prior to end of treatment.	Patients were followed after the last IV dose but no later than 24 hours after the last IV dose.
The Number of Patients With Clinical Cure in Patients With Pathogens Resistant to Ceftazidime at End of Treatment (EOT) Visit in Clinically Evaluable at End of Treatment Analysis Set	The number of patients meeting the cure criteria: the patient is alive and all signs and symptoms of pneumonia have resolved or improved such that all antibacterial therapies for Nosocomial Pneumonia are stopped. No antibacterial therapy other than those outlined by the protocol has been administered for Nosocomial Pneumonia prior to end of treatment.	Patients were followed after the last IV dose but no later than 24 hours after the last IV dose.
The Number of Patients With Clinical Cure in Patients With Pathogens Resistant to Ceftazidime at End of Treatment (EOT) Visit in Microbiologically Evaluable at End of Treatment Analysis Set	The number of patients meeting the cure criteria: the patient is alive and all signs and symptoms of pneumonia have resolved or improved such that all antibacterial therapies for Nosocomial Pneumonia are stopped. No antibacterial therapy other than those outlined by the protocol has been administered for Nosocomial Pneumonia prior to end of treatment.	Patients were followed after the last IV dose but no later than 24 hours after the last IV dose.
The Number of Patients With Clinical Cure in Patients With Pathogens Resistant to Ceftazidime at Test-of-cure (TOC) Visit in Clinically Modified Intent-to-treat Analysis Set at Test-of-cure Visit	The number of patients meeting the cure criteria: the patient was not a clinical failure at end of treatment and the patient is alive and all signs and symptoms of pneumonia have resolved or improved to an extent that no antibacterial therapy for Nosocomial Pneumonia was taken between end of treatment and test-of-cure inclusive.	At the test-of-cure (TOC) visit (Day 21 to 25)
The Number of Patients With Clinical Cure in Patients With Pathogens Resistant to Ceftazidime at Test-of-cure (TOC) Visit in Clinically Evaluable at Test-of-cure Analysis Set	The number of patients meeting the cure criteria: the patient was not a clinical failure at end of treatment and the patient is alive and all signs and symptoms of pneumonia have resolved or improved to an extent that no antibacterial therapy for Nosocomial Pneumonia was taken between end of treatment and test-of-cure inclusive.	At the test-of-cure (TOC) visit (Day 21 to 25)
The Number of Patients With Clinical Cure in Patients With Pathogens Resistant to Ceftazidime at Test-of-cure (TOC) Visit in Microbiologically Evaluable at Test-of-cure Analysis Set	The number of patients meeting the cure criteria: the patient was not a clinical failure at end of treatment and the patient is alive and all signs and symptoms of pneumonia have resolved or improved to an extent that no antibacterial therapy for Nosocomial Pneumonia was taken between end of treatment and test-of-cure inclusive.	At the test-of-cure (TOC) visit (Day 21 to 25)
Number of Patients With a Favorable Per-patient Microbiologic Response in Patients With Pathogens Resistant to Ceftazidime at End of Treatment (EOT) Visit in Microbiologically Modified Intent-to-treat Analysis Set at End of Treatment Visit	Per-patient "favorable" response indicates that all of the patient's baseline pathogens are "eradicated" or "presumed eradicated". Eradication is defined as: source specimen demonstrates absence of the original baseline pathogen. Presumed eradication is defined as: source specimen was not available to culture and the patient was assessed as a clinical cure.	Patients were followed after the last IV dose but no later than 24 hours after the last IV dose.
Number of Patients With a Favorable Per-patient Microbiologic Response in Patients With Pathogens Resistant to Ceftazidime at End of Treatment (EOT) Visit in Extended Microbiologically Evaluable at End of Treatment Analysis Set	Per-patient "favorable" response indicates that all of the patient's baseline pathogens are "eradicated" or "presumed eradicated". Eradication is defined as: source specimen demonstrates absence of the original baseline pathogen. Presumed eradication is defined as: source specimen was not available to culture and the patient was assessed as a clinical cure.	Patients were followed after the last IV dose but no later than 24 hours after the last IV dose.
Number of Patients With a Favorable Per-patient Microbiologic Response in Patients With Pathogens Resistant to Ceftazidime at End of Treatment (EOT) Visit in Microbiologically Evaluable at End of Treatment Analysis Set	Per-patient "favorable" response indicates that all of the patient's baseline pathogens are "eradicated" or "presumed eradicated". Eradication is defined as: source specimen demonstrates absence of the original baseline pathogen. Presumed eradication is defined as: source specimen was not available to culture and the patient was assessed as a clinical cure.	Patients were followed after the last IV dose but no later than 24 hours after the last IV dose.
Number of Patients With a Favorable Per-patient Microbiologic Response in Patients With Pathogens Resistant to Ceftazidime at Test-of-cure (TOC) Visit in Microbiologically Modified Intent-to-treat Analysis Set at Test-of-cure Visit	Per-patient "favorable" response indicates that all of the patient's baseline pathogens are "eradicated" or "presumed eradicated". Eradication is defined as: source specimen demonstrates absence of the original baseline pathogen. Presumed eradication is defined as: source specimen was not available to culture and the patient was assessed as a clinical cure.	At the test-of-cure (TOC) visit (Day 21 to 25)
Number of Patients With a Favorable Per-patient Microbiologic Response in Patients With Pathogens Resistant to Ceftazidime at Test-of-cure (TOC) Visit in Extended Microbiologically Evaluable at Test-of-cure Analysis Set	Per-patient "favorable" response indicates that all of the patient's baseline pathogens are "eradicated" or "presumed eradicated". Eradication is defined as: source specimen demonstrates absence of the original baseline pathogen. Presumed eradication is defined as: source specimen was not available to culture and the patient was assessed as a clinical cure.	At the test-of-cure (TOC) visit (Day 21 to 25)
Number of Patients With a Favorable Per-patient Microbiologic Response in Patients With Pathogens Resistant to Ceftazidime at Test-of-cure (TOC) Visit in Microbiologically Evaluable at Test-of-cure Analysis Set	Per-patient "favorable" response indicates that all of the patient's baseline pathogens are "eradicated" or "presumed eradicated". Eradication is defined as: source specimen demonstrates absence of the original baseline pathogen. Presumed eradication is defined as: source specimen was not available to culture and the patient was assessed as a clinical cure.	At the test-of-cure (TOC) visit (Day 21 to 25)
The Number of Favorable Per-pathogen Microbiologic Responses in Patients With Pathogens Resistant to Ceftazidime at End of Treatment (EOT) Visit in Microbiologically Modified Intent-to-treat Analysis Set at End of Treatment Visit	The number of patients with a favorable per-pathogen microbiological response: favorable microbiological response includes: Eradication where, source specimen demonstrates absence of the original baseline pathogen. Presumed eradication where, source specimen was not available to culture and the patient was assessed as a clinical cure.	Patients were followed after the last IV dose but no later than 24 hours after the last IV dose.
The Number of Favorable Per-pathogen Microbiologic Responses in Patients With Pathogens Resistant to Ceftazidime at End of Treatment (EOT) Visit in Extended Microbiologically Evaluable at End of Treatment Analysis Set	The number of patients with a favorable per-pathogen microbiological response: favorable microbiological response includes: Eradication where, source specimen demonstrates absence of the original baseline pathogen. Presumed eradication where, source specimen was not available to culture and the patient was assessed as a clinical cure.	Patients were followed after the last IV dose but no later than 24 hours after the last IV dose.
The Number of Favorable Per-pathogen Microbiologic Responses in Patients With Pathogens Resistant to Ceftazidime at End of Treatment (EOT) Visit in Microbiologically Evaluable at End of Treatment Analysis Set	The number of patients with a favorable per-pathogen microbiological response: favorable microbiological response includes: Eradication where, source specimen demonstrates absence of the original baseline pathogen. Presumed eradication where, source specimen was not available to culture and the patient was assessed as a clinical cure.	Patients were followed after the last IV dose but no later than 24 hours after the last IV dose.
The Number of Favorable Per-pathogen Microbiologic Responses in Patients With Pathogens Resistant to Ceftazidime at Test-of-cure (TOC) Visit in Microbiologically Modified Intent-to-treat Analysis Set at Test-of-cure Visit	The number of patients with a favorable per-pathogen microbiological response: favorable microbiological response includes: Eradication where, source specimen demonstrates absence of the original baseline pathogen. Presumed eradication where, source specimen was not available to culture and the patient was assessed as a clinical cure.	At the test-of-cure (TOC) visit (Day 21 to 25)
The Number of Favorable Per-pathogen Microbiologic Responses in Patients With Pathogens Resistant to Ceftazidime at Test-of-cure (TOC) Visit in Extended Microbiologically Evaluable at Test-of-cure Analysis Set	The number of patients with a favorable per-pathogen microbiological response: favorable microbiological response includes: Eradication where, source specimen demonstrates absence of the original baseline pathogen. Presumed eradication where, source specimen was not available to culture and the patient was assessed as a clinical cure.	At the test-of-cure (TOC) visit (Day 21 to 25)
The Number of Favorable Per-pathogen Microbiologic Responses in Patients With Pathogens Resistant to Ceftazidime at Test-of-cure (TOC) Visit in Microbiologically Evaluable at Test-of-cure Analysis Set	The number of patients with a favorable per-pathogen microbiological response: favorable microbiological response includes: Eradication where, source specimen demonstrates absence of the original baseline pathogen. Presumed eradication where, source specimen was not available to culture and the patient was assessed as a clinical cure.	At the test-of-cure (TOC) visit (Day 21 to 25)
The Number of Patients With Death Due to Any Cause (All-cause Mortality) at Test-of-cure (TOC) Visit in Microbiologically Modified Intent-to-treat Analysis Set at Test-of-cure Visit	The number of patients with death due to any cause (all-cause mortality) in microbiologically modified intent-to-treat analysis set at test-of-cure visit.	At the test-of-cure (TOC) visit (Day 21 to 25)
The Number of Patients With Death Due to Any Cause (All-cause Mortality) at Test-of-cure (TOC) Visit in Clinically Modified Intent-to-treat Analysis Set at Test-of-cure Visit	The number of patients with death due to any cause (all-cause mortality) in clinically modified intent-to-treat analysis set at test-of-cure visit.	At the test-of-cure (TOC) visit (Day 21 to 25)
The Number of Patients With Death Due to Any Cause (All-cause Mortality) at Test-of-cure (TOC) Visit in the Clinically Evaluable at Test-of-cure Analysis Set	The number of patients with death due to any cause (all-cause mortality) in the clinically evaluable at test-of-cure analysis set.	At the test-of-cure (TOC) visit (Day 21 to 25)
The Number of Patients With Death Due to Any Cause (All-cause Mortality) in Microbiologically Modified Intent-to-treat Analysis Set at Day 28	The number of patients with death due to any cause (all-cause mortality) in microbiologically modified intent-to-treat analysis set at day 28.	at Day 28 from randomization
The Number of Patients With Death Due to Any Cause (All-cause Mortality) in Clinically Modified Intent-to-treat Analysis Set at Day 28	The number of patients with death due to any cause (all-cause mortality) in clinically modified intent-to-treat analysis set at day 28.	at Day 28 from randomization
The Number of Patients With Death Due to Any Cause (All-cause Mortality) in the Clinically Evaluable at Test-of-cure Analysis Set at Day 28	The number of patients with death due to any cause (all-cause mortality) in the clinically evaluable at test-of-cure analysis set at day 28.	at Day 28 from randomization
The Number of Patients Discharged From Hospital up to Test-of-cure (TOC) Visit in Microbiologically Modified Intent-to-treat Analysis Set	The number of patients discharged from hospital in microbiologically modified intent-to-treat analysis set.	up to 25 days from randomization
The Number of Patients Discharged From Hospital up to Test-of-cure (TOC) Visit in the Clinically Modified Intent-to-treat Analysis Set	The number of patients discharged from hospital in the clinically modified intent-to-treat analysis set.	up to 25 days from randomization
The Number of Patients Discharged From Hospital up to Test-of-cure (TOC) Visit in the Clinically Evaluable at Test-of-cure Analysis Set	The number of patients discharged from hospital in the clinically evaluable at test-of-cure analysis set.	up to 25 days from randomization

Collaborators and Investigators

• Sponsor: Pfizer
• Investigators: Study Director: Joseph Chow, MD, FIDSA, AstraZeneca

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.
• Tichy E, Torres A, Bassetti M, Kongnakorn T, Di Virgilio R, Irani P, Charbonneau C. Cost-effectiveness Comparison of Ceftazidime/Avibactam Versus Meropenem in the Empirical Treatment of Hospital-acquired Pneumonia, Including Ventilator-associated Pneumonia, in Italy. Clin Ther. 2020 May;42(5):802-817. doi: 10.1016/j.clinthera.2020.03.014. Epub 2020 Apr 27.
• Stone GG, Bradford PA, Tawadrous M, Taylor D, Cadatal MJ, Chen Z, Chow JW. In Vitro Activity of Ceftazidime-Avibactam against Isolates from Respiratory and Blood Specimens from Patients with Nosocomial Pneumonia, Including Ventilator-Associated Pneumonia, in a Phase 3 Clinical Trial. Antimicrob Agents Chemother. 2020 Apr 21;64(5):e02356-19. doi: 10.1128/AAC.02356-19. Print 2020 Apr 21.
• Torres A, Zhong N, Pachl J, Timsit JF, Kollef M, Chen Z, Song J, Taylor D, Laud PJ, Stone GG, Chow JW. Ceftazidime-avibactam versus meropenem in nosocomial pneumonia, including ventilator-associated pneumonia (REPROVE): a randomised, double-blind, phase 3 non-inferiority trial. Lancet Infect Dis. 2018 Mar;18(3):285-295. doi: 10.1016/S1473-3099(17)30747-8. Epub 2017 Dec 16.

Study record dates

Study Major Dates

• Study Start: April 1, 2013
• Primary Completion (ACTUAL): January 1, 2016
• Study Completion (ACTUAL): January 1, 2016

Study Registration Dates

• First Submitted: February 28, 2013
• First Submitted That Met QC Criteria: March 8, 2013
• First Posted (ESTIMATE): March 11, 2013

Study Record Updates

• Last Update Posted (ACTUAL): September 6, 2017
• Last Update Submitted That Met QC Criteria: September 1, 2017
• Last Verified: September 1, 2017

More Information

Terms related to this study

• Keywords: Physiological Effects of Drugs; Ceftazidime,; Meropenem,; Anti-Bacterial Agents,; Anti-Infective Agents,; Therapeutic Uses,; Pharmacologic Actions,
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Lung Diseases; Disease Attributes; Cross Infection; Iatrogenic Disease; Healthcare-Associated Pneumonia; Pneumonia; Pneumonia, Ventilator-Associated; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Anti-Bacterial Agents; beta-Lactamase Inhibitors; Meropenem; Avibactam; Ceftazidime; Avibactam, ceftazidime drug combination
• Other Study ID Numbers: D4281C00001