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

Purpose

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

Condition	Intervention	Phase
Nosocomial Pneumonia (NP), Ventilator-associated Pneumonia (VAP)	Drug: ceftazidime-avibactam Drug: meropenem	Phase 3

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	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

Resource links provided by NLM:

MedlinePlus related topics: Pneumonia

Drug Information available for: Ceftazidime sodium Ceftazidime Meropenem

U.S. FDA Resources

Further study details as provided by AstraZeneca:

Primary Outcome Measures:

The proportion of patients with clinical cure in the clinically modified intent-to-treat and clinically evaluable analysis sets (co-primary analyses) [ Time Frame: up to 25 days from randomization ] [ Designated as safety issue: No ]
21st - 25th day from randomization

Secondary Outcome Measures:

The proportion of patients with clinical cure in the microbiologically modified intent-to-treat, microbiologically evaluable and extended microbiologically evaluable analysis sets [ Time Frame: up to 25 days from randomization ] [ Designated as safety issue: No ]
21st-25th day from randomization
The proportion of patients with clinical cure in clinically modified intent-to-treat, clinically evaluable, microbiologically modified intent-to-treat, microbiologically evaluable, extended microbiologically evaluable analysis sets [ Time Frame: up to 14 days from randomization ] [ Designated as safety issue: No ]
The proportion of patients with a favorable per-patient microbiologic response in microbiologically modified intent-to-treat, microbiologically evaluable, extended microbiologically evaluable analysis sets [ Time Frame: up to 14 days from randomization and 21 to 25 from randomization ] [ Designated as safety issue: No ]
The proportion of favorable per-pathogen microbiologic responses in microbiologically modified intent-to-treat, microbiologically evaluable and extended microbiologically evaluable analysis sets [ Time Frame: up to 14 days from randomization and 21 to 25 from randomization ] [ Designated as safety issue: No ]
The proportion of favorable per-pathogen microbiologic responses by minimum inhibitory concentration categories in microbiologically modified intent-to-treat, microbiologically evaluable and extended-microbiologically evaluable analysis sets [ Time Frame: up to 14 days from randomization and 21 to 25 from randomization ] [ Designated as safety issue: No ]
The proportion of patients with clinical cure in patients with pathogens resistant to ceftazidime in clinically evaluable, clinically modified intent-to-treat, microbiologically evaluable analysis sets [ Time Frame: up to 14 days from randomization and 21 to 25 from randomization ] [ Designated as safety issue: No ]
Proportion of patients with a favorable per-patient microbiologic response in patients with pathogens resistant to ceftazidime in microbiologically modified intent-to-treat, microbiologically evaluable, extended microbiologically evaluable analysis sets [ Time Frame: up to 14 days from randomization and 21 to 25 from randomization ] [ Designated as safety issue: No ]
The proportion of favorable per-pathogen microbiologic responses in patients with pathogens resistant to ceftazidime in microbiologically modified intent-to-treat, microbiologically evaluable and extended microbiologically evaluable analysis sets [ Time Frame: up to 14 days from randomization and 21 to 25 from randomization ] [ Designated as safety issue: No ]
The proportion of patients with death due to any cause (all-cause mortality) in the clinically evaluable, clinically modified intent-to-treat and microbiologically modified intent-to-treat analysis sets [ Time Frame: at Day 21 to 25 from randomization and Day 28 from randomization ] [ Designated as safety issue: Yes ]
The proportion of patients discharged from hospital in the clinically evaluable, clinically modified intent-to-treat and microbiologically modified intent-to-treat analysis sets [ Time Frame: up to 25 days from randomization ] [ Designated as safety issue: No ]
21st - 25th day from randomization
Safety and tolerability by incidence and severity of adverse events and serious adverse events, mortality, reasons for discontinuations of study therapy, vital signs, physical exams, electrocardiogram parameters, and clinical laboratory tests [ Time Frame: up to 28 days from randomization ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	1600
Study Start Date:	March 2013
Estimated Study Completion Date:	June 2016
Estimated Primary Completion Date:	June 2016 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 1 Intra-Venous treatment	Drug: ceftazidime-avibactam 2000mg ceftazidime plus 500mg avibactam
Active Comparator: 2 Intra-Venous treatment	Drug: meropenem 1000mg of Meropenem

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

Eligibility

Ages Eligible for Study:	18 Years to 90 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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 precludes evaluation of therapeutic response (including, but not limited to, 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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01808092

Contacts

Contact: AstraZeneca Clinical Study Information

800-236-9933

information.center@astrazeneca.com

Sponsors and Collaborators

AstraZeneca

Investigators

Study Director:

Paul Newell, MBBS, MRCP

AstraZeneca

More Information

No publications provided

Responsible Party:	AstraZeneca
ClinicalTrials.gov Identifier:	NCT01808092 History of Changes
Other Study ID Numbers:	D4281C00001
Study First Received:	February 28, 2013
Last Updated:	March 8, 2013
Health Authority:	Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica Brazil: National Health Surveillance Agency Bulgaria: Bulgarian Drug Agency Chile: Instituto de Salud Publica de Chile China: Food and Drug Administration Czech Republic: State Institute for Drug Control France: French Health Products Safety Agency Hungary: National Institute of Pharmacy India: Drugs Controller General of India Italy: National Institute of Health Japan: Pharmaceutical and Medical Devices Agency Korea: Food and Drug Administration Mexico: Federal Commission for Sanitary Risks Protection Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products Russian Federation: Ministry of Health and Social Development of the Russian Federation South Africa: Medicines Control Council of South Africa Spain: Spanish Agency of Medicines Turkey: Ministry of Health Ukraine: State Pharmacological Center - Ministry of Health Vietnam: Ho Chi Minh City Health Service, Ministry of Health Slovakia: State Institute for Drug Control UK: Department of Health, Food Standards Agency, Medicines and Healthcare Products Regulatory Agency, National Health Service, Research Ethics Committee Peru: Ministry of Health

Keywords provided by AstraZeneca:

Ceftazidime,
Meropenem,
Anti-Bacterial Agents,
Anti-Infective Agents,

Therapeutic Uses,
Pharmacologic Actions,
Physiological Effects of Drugs

Additional relevant MeSH terms:

Pneumonia
Pneumonia, Ventilator-Associated
Lung Diseases
Respiratory Tract Diseases
Respiratory Tract Infections
Cross Infection
Infection
Ventilator-Induced Lung Injury

Lung Injury
Meropenem
Anti-Infective Agents
Ceftazidime
Physiological Effects of Drugs
Therapeutic Uses
Pharmacologic Actions
Anti-Bacterial Agents

ClinicalTrials.gov processed this record on May 23, 2013