Status:
COMPLETED
A Study to Determine the Efficacy, Safety and Tolerability of Aztreonam-Avibactam (ATM-AVI) ± Metronidazole (MTZ) Versus Meropenem (MER) ± Colistin (COL) for the Treatment of Serious Infections Due to Gram Negative Bacteria.
Lead Sponsor:
Pfizer
Collaborating Sponsors:
Innovative Medicines Initiative
Biomedical Advanced Research and Development Authority
Conditions:
Complicated Intra-abdominal Infection
Hosptial Acquired Pneumonia
Eligibility:
All Genders
18+ years
Phase:
PHASE3
Brief Summary
A Phase 3 comparative study to determine the efficacy, safety and tolerability of Aztreonam-Avibactam (ATM-AVI) ± Metronidazole (MTZ) versus Meropenem (MER) ± Colistin (COL) for the treatment of serio...
Detailed Description
A Phase 3 Prospective, Randomized, Multicenter, Open Label, Central Assessor Blinded, Parallel Group, Comparative Study To Determine The Efficacy, Safety And Tolerability Of Aztreonam-Avibactam (ATM-A...
Eligibility Criteria
Inclusion
- Inclusion Criteria:
- All subjects:
- Male or female from 18 years of age
- Provision of informed consent
- Confirmed diagnosis of HAP/VAP or cIAI requiring iv antibiotic treatment
- Female patients are authorized to participate in this clinical study if criteria concerning pregnancy avoidance stated in the protocol are met and negative pregnancy test
- Additional for cIAI:
- Diagnosis of cIAI, EITHER:
- Intra-operative/postoperative enrolment with visual confirmation of cIAI. OR Preoperative enrollment with evidence of systemic inflammatory response, physical and radiological findings consistent with cIAI; confirmation of cIAI at time of surgery within 24 hours of study entry
- Surgical intervention within 24 hours (before or after) the administration of the first dose of study drug
- Additional for HAP/VAP:
- Onset symptoms \> 48h after admission to or \<7 days after discharge from an inpatient care facility
- New or worsening infiltrate on CXR or CT scan
- Clinical signs and symptoms and laboratory findings consistent with HAP/VAP
- Respiratory specimen obtained for Gram stain and culture following onset of symptoms and prior to randomisation
- Exclusion criteria:
- All subjects:
- APACHE II score \> 30
- Confirmed or suspected infection caused by Gram-negative species not expected to respond to study drug, or Gram-positive species
- Receipt of \>24 hr systemic antibiotic within 48h prior to randomisation (exception in case of treatment failure)
- History of serious allergy, hypersensitivity (eg, anaphylaxis), or any serious reaction to aztreonam, carbapenem,monobactam or other β-lactam antibiotics, avibactam, nitroimidazoles or metronidazole, or any of the excipients of the study drugs
- Known Clostridium difficle associated diarrhoea
- Requirement for effective concomitant systemic antibacterials or antifungals
- Creatinine clearance ≤15 ml/min or requirement or expectation for renal replacement therapy
- Acute hepatitis, cirrhosis, acute hepatic failure, chronic hepatic failure
- Hepatic disease as indicated by AST or ALT \>3 × ULN. Patients with AST and/or ALT up to 5 × ULN are eligible if acute and documented by the investigator as being directly related infectious process
- Patient has a total bilirubin \>2 × ULN, unless isolated hyperbilirubinemia is directly related to infectious process or due to known Gilbert's disease
- ALP \>3 × ULN. Patients with values \>3 × ULN and \<5 x ULN are eligible if acute and directly related to the infectious process being treated
- Absolute neutrophil count \<500/mm3
- Pregnant or breastfeeding or if of child bearing potential, not using a medically accepted effective method of birth control.
- Any other condition that may confound the results of the study or pose additional risks to the subject
- Unlikely to comply with protocol
- History of epilepsy or seizure disorders excluding febrile seizures of childhood
- Additional for cIAI
- Diagnosis of abdominal wall abscess; small bowel obstruction or ischemic bowel disease without perforation; traumatic bowel perforation with surgery within 12 hours of diagnosis; perforation of gastroduodenal ulcer with surgery \< 24 hours of diagnosis primary etiology is not likely to be infectious
- Simple cholecystitis, gangrenous cholecystitis without rupture, simple appendicitis, acute suppurative cholangitis, infected necrotizing pancreatitis, pancreatic abscess
- Prior liver, pancreas or small-bowel transplant
- Staged abdominal repair (STAR), open abdomen technique or marsupialisation
- Additional for HAP/VAP
- APACHE II score \< 10
- Known or high likelihood of Gram-positive monomicrobial infection
- Lung abscess, pleural empyema, post-obstructive pneumonia
- Lung or heart transplant
- Myasthenia gravis
Exclusion
Key Trial Info
Start Date :
April 5 2018
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
February 23 2023
Estimated Enrollment :
422 Patients enrolled
Trial Details
Trial ID
NCT03329092
Start Date
April 5 2018
End Date
February 23 2023
Last Update
December 10 2024
Active Locations (157)
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1
Banner University Medical Center - Tucson
Tucson, Arizona, United States, 85719
2
Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
Torrance, California, United States, 90502
3
Harbor-UCLA Medical Center
Torrance, California, United States, 90509
4
Southern Illinois University School of Medicine
Springfield, Illinois, United States, 62702