Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

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

This study has been completed.
Sponsor:
Collaborator:
Cerexa, Inc.
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT01500239
First received: December 22, 2011
Last updated: June 3, 2014
Last verified: April 2014
  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:


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 ]

Enrollment: 577
Study Start Date: April 2012
Study Completion Date: April 2014
Primary Completion Date: April 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 if at least one of the following criteria are met:

    1. Surgical sterilization
    2. Age ≥50 years and postmenopausal as defined by amenorrhea for 12 months or more following cessation of all exogenous hormonal treatments
    3. Age <50 years and postmenopausal as defined by documented LH and FSH levels in the postmenopausal range PLUS amenorrhea for 12 months or more following cessation of all exogenous hormonal treatments
    4. Patient has a negative serum pregnancy test (serum ß-human chorionic gonadotropin [ß-hCG]) within 1 day prior to study entry, and agrees to use highly effective contraception methods during treatment and for at least 7 days after last dose of IV study therapy.
  • 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
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: NCT01500239

  Show 63 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: June 3, 2014
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 Pública 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:
Communicable Diseases
Infection
Intraabdominal Infections
Ceftazidime
Meropenem
Metronidazole
Anti-Bacterial Agents
Anti-Infective Agents
Antiparasitic Agents
Antiprotozoal Agents
Pharmacologic Actions
Radiation-Sensitizing Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on November 24, 2014