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

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by AstraZeneca
Sponsor:
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT01808092
First received: February 28, 2013
Last updated: September 17, 2014
Last verified: September 2014
  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:


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: 1494
Study Start Date: April 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, 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.
  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: NCT01808092

Contacts
Contact: AstraZeneca Clinical Study Information 800-236-9933 ClinicalTrialTransparency@astrazeneca.com

  Show 202 Study Locations
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: September 17, 2014
Health Authority: Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
Brazil: National Health Surveillance Agency
Bulgaria: Bulgarian Drug Agency
Chile: Instituto de Salud Pública 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
Taiwan: Department of Health / Institutional Review Board / National Bureau of Controlled Drugs
Thailand: Ethical Committee / Food and Drug Administration / Khon Kaen University Ethics Committee for Human Research / Ministry of Public Health
Philippines: Bureau of Food and Drugs / Department 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
Ceftazidime
Meropenem
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on October 19, 2014