A Study Comparing Ceftazidime-Avibactam+Metronidazole Versus Meropenem in Adults With Complicated Intra-abdominal Infections - Full Text View

Purpose

The purpose of this study is to evaluate the effects of Ceftazidime Avibactam plus Metronidazole compared to Meropenem for treating hospitalized patients with complicated intra-abdominal infections.

Condition	Intervention	Phase
Complicated Intra-Abdominal Infection	Drug: CAZ-AVI Drug: Metronidazole 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, Multicenter, Double Blind, Double-Dummy, Parallel-Group, Comparative Study to Determine the Efficacy, Safety, and Tolerability of Ceftazidime Avibactam Plus Metronidazole Versus Meropenem in the Treatment of Complicated Intra-Abdominal Infections In Hospitalized Adults

Resource links provided by NLM:

Drug Information available for: Metronidazole Metronidazole benzoate Metronidazole hydrochloride Ceftazidime sodium Ceftazidime Meropenem

U.S. FDA Resources

Further study details as provided by AstraZeneca:

Primary Outcome Measures:

Clinical Cure as Measured by proportion of patients meeting cure criteria in the microbiological modified Intent-To-Treat analysis set. [ Time Frame: 28 to 35 days after start of study drug ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

The proportion of patients with clinical cure in the microbiologically evaluable and extended microbiologically evaluable analysis set [ Time Frame: 28 to 35 days after start of study drug ] [ Designated as safety issue: No ]
The proportion of patients with clinical cure in the microbiological modified intent-to-treat, microbiologically evaluable, and extended microbiologically evaluable analysis sets [ Time Frame: within 24 hours after last dose of study drug and 42 to 49 days after start of study drug ] [ Designated as safety issue: No ]
The proportion of patients with clinical cure in the clinically evaluable analysis set [ Time Frame: within 24 hours after last dose of study drug, 28 to 35 days after start of study drug and 42 to 49 days after start of study drug ] [ Designated as safety issue: No ]
The proportion of patients with a favorable per-patient microbiological response in the microbiological modified intent to treat, microbiologically evaluable, and extended microbiologically evaluable analysis sets [ Time Frame: within 24 hours after last dose of study drug, 28 to 35 days after start of study drug and 42 to 49 days after start of study drug ] [ Designated as safety issue: No ]
The proportion of favorable per-pathogen microbiological response in the microbiological modified intent to treat, microbiologically evaluable, and extended microbiologically evaluable analysis sets [ Time Frame: within 24 hours after last dose of study drug, 28 to 35 days after start of study drug and 42 to 49 days after start of study drug visits ] [ Designated as safety issue: No ]
The favorable per-pathogen microbiologic response by minimum inhibitory concentration (MIC)categories in the microbiological modified intent to treat, microbiologically evaluable,and extended microbiologically evaluable analysis sets [ Time Frame: within 24 hours after last dose of study drug, 28 to 35 days after start of study drug and 42 to 49 days after start of study drug visits ] [ Designated as safety issue: No ]
Favorable per-patient clinical response & microbiological response for patients infected with ceftazidime-resistant pathogens in microbiological modified intent to treat, microbiologically evaluable & extended microbiologically evaluable analysis sets [ Time Frame: 28 to 35 days after start of study drug ] [ Designated as safety issue: No ]
Proportion of patients with favorable per-pathogen microbiological response for patients infected with ceftazidime-resistant pathogens in microbiological modified ITT, microbiologically evaluable and extended microbiologically evaluable analysis sets [ Time Frame: 28 to 35 days after start of study drug ] [ Designated as safety issue: No ]
The time to first defervescence in the clinically evaluable, microbiologically evaluable, and extended microbiologically evaluable analysis sets for patients who have fever at study entry [ Time Frame: 1 to 14 days after start of study drug ] [ Designated as safety issue: No ]
The safety and tolerability 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 50 days) ] [ Designated as safety issue: Yes ]
Pharmacokinetics: maximum concentration (Cmax), minimum concentration, area under the plasma concentration time curve at steady state, and terminal half-life [ 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 ]

Estimated Enrollment:	1106
Study Start Date:	April 2012
Estimated Study Completion Date:	June 2014
Estimated Primary Completion Date:	June 2014 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 1 IV treatment	Drug: CAZ-AVI Ceftazidime 2000 mg and 500 mg of avibactam Drug: Metronidazole 500 mg of Metronidazole
Active Comparator: 2 IV treatment	Drug: Meropenem 1 gram of Meropenem

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 Plus Metronidazole Versus Meropenem in the Treatment of Complicated Intra-Abdominal Infections 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
Female patient is authorized to participate in this clinical study if she has been surgically sterilized or postmenopausal for at least 1 year or her sexual partner has had a vasectomy and must be willing, during treatment and for at least 7 days after last dose of IV study therapy, to practice highly effective methods of birth control
Intraoperative/postoperative enrollment with confirmation (presence of pus within the abdominal cavity) of an intra-abdominal infection associated with peritonitis
Confirmation of infection by surgical intervention within 24 hours of entry: evidence of systemic inflammatory response; physical findings consistent with intra-abdominal infection; supportive radiologic imaging findings of intra-abdominal infections

Exclusion Criteria:

Patient is diagnosed with traumatic bowel perforation undergoing surgery within 12 hours; perforation of gastroduodenal ulcers undergoing surgery within 24 hours. Other intra-abdominal processes in which primary etiology is not likely to be infectious
Patient has abdominal wall abscess or bowel obstruction without perforation or ischemic bowel without perforation
Patient has suspected intra-abdominal infections due to fungus, parasites, virus or tuberculosis
Patient is considered unlikely to survive the 6 to 8 week study period or has a rapidly progressive or terminal illness, including septic shock that is associated with a high risk of mortality

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01500239

Contacts

Contact: AstraZeneca Clinical Study Information	800-236-9933	information.center@astrazeneca.com
Contact: Annette Fisher	1-919-456-4039	Annette.Fisher@ppdi.com

Show 85 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:	NCT01500239 History of Changes
Other Study ID Numbers:	D4280C00005, 2011-003895-35
Study First Received:	December 22, 2011
Last Updated:	April 26, 2013
Health Authority:	Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica Belgium: Federal Agency for Medicinal Products and Health Products Brazil: National Health Surveillance Agency Bulgaria: Bulgarian Drug Agency Chile: Instituto de Salud Publica de Chile 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 India: Drugs Controller General of India Israel: Ministry of Health Italy: National Institute of Health Romania: National Medicines Agency Russia: Ministry of Health of the Russian Federation Spain: Spanish Agency of Medicines Thailand: Food and Drug Administration Turkey: Ministry of Health Ukraine: State Pharmacological Center - Ministry of Health United States: Food and Drug Administration Canada: Health Canada

Keywords provided by AstraZeneca:

cIAI
Ceftazidime
Meropenem
Metronidazole
Anti-Bacterial Agents

Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Physiological Effects of Drugs

Additional relevant MeSH terms:

Meropenem
Anti-Infective Agents
Ceftazidime
Metronidazole
Physiological Effects of Drugs
Therapeutic Uses

Pharmacologic Actions
Anti-Bacterial Agents
Radiation-Sensitizing Agents
Antiprotozoal Agents
Antiparasitic Agents

ClinicalTrials.gov processed this record on May 21, 2013