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

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by AstraZeneca
Sponsor:
Collaborator:
Cerexa, Inc.
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT01644643
First received: June 28, 2012
Last updated: July 2, 2014
Last verified: July 2014
  Purpose

To Evaluate the Effects of Ceftazidime-Avibactam and Best Available Therapy in patients with complicated urinary tract infections and complicated intra-abdominal infections.


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

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-Label, Randomized, Multicenter, Phase III Study of Ceftazidime Avibactam (CAZ-AVI, Formerly CAZ104) and Best Available Therapy for the Treatment of Infections Due to Ceftazidime Resistant Gram Negative Pathogens

Resource links provided by NLM:


Further study details as provided by AstraZeneca:

Primary Outcome Measures:
  • The proportion of patients with clinical cure at the Test of Cure visit in the microbiological intent-to-treat (mMITT) analysis set. [ Time Frame: 7-10 days after last infusion of study therapy ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • The proportion of patients with clinical cure in the microbiological modified intent to treat analysis set. [ Time Frame: Within 24 hours after last infusion of study therapy, 21-35 days after randomization and 28-32 days after randomization ] [ Designated as safety issue: No ]
  • The proportion of patients with clinical cure in the extended microbiologically evaluable analysis set [ Time Frame: Within 24 hours after last infusion of study therapy, 7-10 days after last infusion of study therapy, 21-35 days after randomization, 28-32 days after randomization ] [ Designated as safety issue: No ]
  • The proportion of patients with clinical cure by pathogen (eg, E. coli, Klebsiella spp., Pseudomonas aeruginosa) in the microbiological modified intent to treat analysis set. [ Time Frame: At 7-10 days after last infusion of study therapy ] [ Designated as safety issue: No ]
  • The proportion of patients with clinical cure by resistance mechanism (eg, Klebsiella pneumoniae carbapenemase producer, Extended spectrum β lactamase producer) in the microbiological modified intent to treat analysis set. [ Time Frame: At 7-10 days after last infusion of study therapy ] [ Designated as safety issue: No ]
  • The proportion of patients with clinical cure by entry diagnosis (complicated intra-abdominal infection/complicated urinary tract infection) in the microbiological modified intent to treat analysis set. [ Time Frame: At 7-10 days after last infusion of study therapy ] [ Designated as safety issue: No ]
  • The proportion of patients with clinical cure by pathogen (eg, E. coli, Klebsiella spp., Pseudomonas aeruginosa) in the extended microbiologically evaluable analysis set. [ Time Frame: At 7-10 days after last infusion of study therapy ] [ Designated as safety issue: No ]
  • The proportion of patients with clinical sure by resistance mechanism (eg, Klebsiella pneumoniae carbapenemase producer, Extended spectrum β lactamase producer) in the extended microbiologically evaluable analysis set. [ Time Frame: At 7-10 days after last infusion of study therapy ] [ Designated as safety issue: No ]
  • The proportion of patients with clinical cure by entry diagnosis (complicated intra-abdominal infection/complicated urinary tract infection) in the extended microbiologically evaluable analysis set. [ Time Frame: At 7-10 days after last infusion of study therapy ] [ Designated as safety issue: No ]
  • The proportion of patients with clinical cure by previously failed treatment class (eg, quinolone, β lactam/β lactamase inhibitor, third- or fourth generation cephalosporin, carbapenem), in the microbiological modified intent to treat analysis set. [ Time Frame: At 7-10 days after last infusion of study therapy ] [ Designated as safety issue: No ]
  • The proportion of patients with clinical cure by previously failed treatment class (eg, quinolone, β lactam/β lactamase inhibitor, third- or fourth generation cephalosporin, carbapenem) in the extended microbiologically evaluable analysis set. [ Time Frame: Within 24 hours after last infusion of study therapy, 7-10 days after last infusion of study therapy, 21-35 days after randomization, 28-32 days after randomization ] [ Designated as safety issue: No ]
  • The proportion of patients with favorable per-pathogen microbiological response in the microbiological modified intent to treat analysis set. [ Time Frame: Within 24 hours after last infusion of study therapy, 7-10 days after last infusion of study therapy, 21-35 days after randomization, 28-32 days after randomization ] [ Designated as safety issue: No ]
  • The proportion of patients with favorable per-pathogen microbiological response in the extended microbiologically evaluable analysis set [ Time Frame: Within 24 hours after last infusion of study therapy, 7-10 days after last infusion of study therapy, 21-35 days after randomization, and 28-32 days after randomization ] [ Designated as safety issue: No ]
  • The proportion of patients with a favorable per-patient microbiological response in the microbiological modified intent to treat analysis set. [ Time Frame: With 24 hours after last infusion of study therapy, 7-10 days after last infusion of study therapy, 21-35 days after randomization, and 28-32 days after randomization ] [ Designated as safety issue: No ]
  • The proportion of patients with a favorable per-patient microbiological response in the extended microbiologically evaluable analysis set [ Time Frame: With 24 hours after last infusion of study therapy, 7-10 days after last infusion of study therapy, 21-35 days after randomization, 28-32 days after randomization ] [ Designated as safety issue: No ]
  • The proportion of patients with a favorable microbiological response by resistance mechanism (eg, Klebsiella pneumoniae carbapenemase producer, Extended spectrum β lactamase producer) in the microbiological modified intent to treat analysis set. [ Time Frame: 7-10 days after last infusion of study therapy ] [ Designated as safety issue: No ]
  • The proportion of patients with a favorable microbiological response by resistance mechanism (eg, Klebsiella pneumoniae carbapenemase producer, Extended spectrum β lactamase producer) in the extended microbiologically evaluable analysis set [ Time Frame: 7-10 days after last infusion of study therapy ] [ Designated as safety issue: No ]
  • The proportion of favorable per-pathogen microbiologic response by minimum inhibitory concentration in the microbiological modified intent to treat analysis set. [ Time Frame: Within 24 hours after last infusion of study therapy, 7-10 days after last infusion of study therapy, 21-35 days after randomization, and 28-32 days after randomization ] [ Designated as safety issue: No ]
  • The proportion of favorable per-pathogen microbiologic response by minimum inhibitory concentration in the extended microbiologically evaluable analysis set [ Time Frame: Within 24 hours after last infusion of study therapy, 7-10 days after last infusion of study therapy, 21-35 days after randomization, and 28-32 days after randomization ] [ Designated as safety issue: No ]
  • The number of patients that change or discontinue treatment by reason in the microbiological modified intent to treat population analysis set [ Time Frame: Study Duration [Day 1 through last follow up visit (up to 35 days)] ] [ Designated as safety issue: No ]
  • The 28-day mortality rate in the microbiological modified intent to treat analysis set [ Time Frame: 28 days after randomization ] [ Designated as safety issue: No ]
  • The 28-day mortality rate in the extended microbiologically evaluable analysis set. [ Time Frame: 28 days after randomization ] [ Designated as safety issue: No ]
  • Profile of pharmacokinetic (PK): maximum plasma concentration (Cmax) [ Time Frame: Anytime within 15 minutes prior to or after stopping study drug, anytime between 30 and 90 minutes after stopping study drug, anytime between 300 minutes and 360 minutes after stopping study drug ] [ Designated as safety issue: No ]
  • Profile of pharmacokinetic (PK): minimum plasma concentration (Cmin) [ Time Frame: Anytime within 15 minutes prior to or after stopping study drug, anytime between 30 and 90 minutes after stopping study drug, anytime between 300 minutes and 360 minutes after stopping study drug ] [ Designated as safety issue: No ]
  • Profile of pharmacokinetic (PK): area under plasma concentration time curve at study state (AUC ss) [ Time Frame: Anytime within 15 minutes prior to or after stopping study drug, anytime between 30 and 90 minutes after stopping study drug, anytime between 300 minutes and 360 minutes after stopping study drug ] [ Designated as safety issue: No ]
  • Profile of pharmacokinetic (PK): elimination half-life (t ½) [ Time Frame: Anytime within 15 minutes prior to or after stopping study drug, anytime between 30 and 90 minutes after stopping study drug, anytime between 300 minutes and 360 minutes after stopping study drug ] [ Designated as safety issue: No ]
  • Safety and tolerability profile by incidence and severity of adverse events and serious adverse events, vital signs, clinical laboratory tests, ECGs and physical exams [ Time Frame: Study duration [(from screening visit (Day-1) through last follow up visit (up to 35 days)] ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 400
Study Start Date: January 2013
Estimated Study Completion Date: February 2015
Estimated Primary Completion Date: February 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Ceftazidime - Avibactam ( CAZ-AVI)
IV treatment
Drug: Ceftazidime - Avibactam ( CAZ-AVI)
Ceftazidime 2000 mg and 500 mg of avibactam Patients randomized to receive CAZ-AVI will receive an infusion of CAZ-AVI (2000 mg ceftazidime and 500 mg avibactam) every 8 hours administered by intravenous (IV) infusion in a volume of 100 mL at a constant rate over 120 minutes
Drug: Metronidazole
Anti-infective, 500 mg (cIAI only) Patients randomized to receive CAZ-AVI for cIAI will also receive metronidazole (500 mg) administered by IV infusion in a volume of 100 mL at a constant rate over 60 minutes immediately following the CAZ-AVI infusion
Other Name: Flagyl
Active Comparator: Best Available Therapy
IV treatment
Drug: Best Available Therapy
Patients randomized to receive Best Available Therapy will receive the best available standard of care (SOC) anti-infective therapy for their infection administered in accord with approved local label recommendation

Detailed Description:

An Open-Label, Randomized, Multicenter, Phase III Study of Ceftazidime Avibactam (CAZ-AVI, formerly CAZ104) and Best Available Therapy for the Treatment of Infections Due to Ceftazidime Resistant Gram Negative Pathogens

  Eligibility

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

Inclusion Criteria:

  • Patient must be ≥18 and ≤90 years of age
  • Female patients can participate if they are surgically sterile or completed menopause or females capable of having children and agree not to attempt pregnancy while receiving IV study therapy and for a period of 7 days after
  • Patient has a ceftazidime-resistant Gram negative pathogen that was isolated from an appropriate culture within 5 days prior to study entry (ie, within 5 days prior to Screening; the study-qualifying culture), which was determined to be the causative agent of the entry infection

Exclusion Criteria:

  • Patient has an APACHE II score >30 (cIAI patients only)
  • Patient has an infection due to Gram negative pathogen that is unlikely to respond to CAZ-AVI treatment (eg, Acinetobacter spp., Stenotrophomonas spp.)
  • Patient is receiving hemodialysis or peritoneal dialysis or had a renal transplant Patient is immunocompromised
  • Patient has a rapidly progressive or terminal illness with a high risk of mortality due to any cause, including acute hepatic failure, respiratory failure or severe septic shock such that they are unlikely to survive the 4- to 5-week study period.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

Contacts
Contact: AstraZeneca Clinical Study Information 800-236-9933 ClinicalTrialTransparency@astrazeneca.com
Contact: Leslie Smith 1-910-313-1583 Leslie.Smith@ppdi.com

  Show 174 Study Locations
Sponsors and Collaborators
AstraZeneca
Cerexa, Inc.
Investigators
Study Director: Paul Newell, MBBS, MRCP AstraZeneca
  More Information

No publications provided

Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT01644643     History of Changes
Other Study ID Numbers: D4280C00006, 2012-000726-21
Study First Received: June 28, 2012
Last Updated: July 2, 2014
Health Authority: Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
Australia: Department of Health and Ageing Therapeutic Goods Administration
Belgium: Federal Agency for Medicinal Products and Health Products
Brazil: National Health Surveillance Agency
Bulgaria: Bulgarian Drug Agency
Chile: Instituto de Salud Pública de Chile
Croatia: Ministry of Health and Social Care
Czech Republic: State Institute for Drug Control
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Federal Institute for Drugs and Medical Devices
Greece: National Organization of Medicines
Hungary: National Institute of Pharmacy
India: Drugs Controller General of India
Israel: Ministry of Health
Italy: National Institute of Health
Japan: Pharmaceuticals and Medical Devices Agency
Mexico: Federal Commission for Sanitary Risks Protection
Peru: Ministry of Health
Philippines: Bureau of Food and Drugs
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Romania: National Medicines Agency
Russia: Ministry of Health of the Russian Federation
South Africa: Medicines Control Council
South Korea: Korea Food and Drug Administration (KFDA)
Spain: Spanish Agency of Medicines
Taiwan : Food and Drug Administration
Turkey: Ministry of Health
Ukraine: State Pharmacological Center - Ministry of Health
United States: Food and Drug Administration

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

Additional relevant MeSH terms:
Infection
Communicable Diseases
Urinary Tract Infections
Intraabdominal Infections
Urologic Diseases
Metronidazole
Ceftazidime
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antiprotozoal Agents
Antiparasitic Agents
Radiation-Sensitizing Agents
Anti-Bacterial Agents

ClinicalTrials.gov processed this record on September 16, 2014