A Study to Determine the Effect of Aztreonam-Avibactam Versus Meropenem for the Treatment of Serious Infections Due to Gram Negative Bacteria.
Phase 3
Completed
- Conditions
- Unspecified bacterial pneumonia, (2) ICD-10 Condition: K650||Generalized (acute) peritonitis,
- Registration Number
- CTRI/2018/09/015762
- Lead Sponsor
- Pfizer Limited
- Brief Summary
A Phase 3 comparative study to determine theefficacy, safety and tolerability of Aztreonam-Avibactam (ATM-AVI) ± Metronidazole(MTZ) versus Meropenem (MER) ± Colistin (COL) for the treatment of seriousinfections due to Gram negative bacteria.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- All
- Target Recruitment
- 425
Inclusion Criteria
- Inclusion Criteria: All subjects: 1.
- Male or female from 18 years of age 2.
- Provision of informed consent 3.
- Confirmed diagnosis of HAP/VAP or cIAI requiring iv antibiotic treatment 4.
- 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: 1.
- 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 2.
- Surgical intervention within 24 hours (before or after) the administration of the first dose of study drug Additional for HAP/VAP: 1.
- Onset symptoms > 48h after admission to or <7 days after discharge from an inpatient care facility 2.
- New or worsening infiltrate on CXR or CT scan 3.
- Clinical signs and symptoms and laboratory findings consistent with HAP/VAP 4.
- Respiratory specimen obtained for Gram stain and culture following onset of symptoms and prior to randomisation.
Exclusion Criteria
- All subjects: 1.
- APACHE II score > 30 2.
- Confirmed or suspected infection caused by Gram-negative species not expected to respond to study drug, or Gram-positive species 3.
- Receipt of >24 hr systemic antibiotic within 48h prior to randomisation (exception in case of treatment failure) 4.
- History of serious allergy, hypersensitivity (eg, anaphylaxis), or any serious reaction to aztreonam, carbapenem, monobactam or other ß-lactam antibiotics, avibactam, nitroimidazoles or metronidazole, or any of the excipients of the study drugs 5.
- Known Clostridium difficle associated diarrhoea 6.
- Requirement for effective concomitant systemic antibacterials or antifungals 7.
- Creatinine clearance is equals to 15 ml per min or requirement or expectation for renal replacement therapy 8.
- Acute hepatitis, cirrhosis, acute hepatic failure, chronic hepatic failure 9.
- Hepatic disease as indicated by AST or ALT greater than 3 X ULN.
- Patients with AST and or or ALT up to 5 X ULN are eligible if acute and documented by the investigator as being directly related infectious process 10.
- Patient has a total bilirubin greater than 2 X ULN unless isolated hyperbilirubinemia is directly related to infectious process or due to known Gilberts disease.
- ALP greater than 3 X ULN.
- Patients with values greater than 3 X ULN and Less than 5 X ULN are eligible if acute and directly related to the infectious process being treated 12.
- Absolute neutrophil count less than 500 per 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 15.
- Unlikely to comply with protocol 16.
- History of epilepsy or seizure disorders excluding febrile seizures of childhood Additional for cIAI 1.
- 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 h 2.
- Simple cholecystitis, gangrenous cholecystitis without rupture, simple appendicitis, acute suppurative cholangitis, infected necrotizing pancreatitis, pancreatic abscess 3.
- Staged abdominal repair (STAR), open abdomen technique or marsupialisation Additional for HAP/VAP 1.
- APACHE II score < 10 2.
- Known or high likelihood of Gram-positive monomicrobial infection 3.
- Lung abscess, pleural empyema, post-obstructive pneumonia 4.
- Lung or heart transplant 5.
- Myasthenia gravis.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method proportion of subjects with clinical cure in the ITT and CE analysis sets Test of Cure (TOC) visit, Day 28 ± 3 days
- Secondary Outcome Measures
Name Time Method PK of AVI Days 1 and 4 PK/PD relationship between exposure and clinical response for ATM AVI±MTZ in the popPK analysis set Test of Cure (TOC) visit, Day 28 ± 3 days Proportion of subjects who died Day 28 Proportion of subjects with a favorable per subject microbiological response in the micro ITT and ME analysis sets Test of Cure (TOC) visit, Day 28± 3 days Proportion of subjects with clinical cure by infection type in the ITT and CE analysis sets Test of Cure (TOC) visit, Day 28± 3 days Proportion of subjects with clinical cure for subjects with MBL positive pathogens in the micro ITT and ME analysis sets. Test of Cure (TOC) visit, Day 28± 3 days Description of safety in terms of adverse events Throughout study to Late Follow Up visit (Day 45 ± 3 days) PK of ATM Days 1 and 4 Proportion of subjects with clinical cure in the m-ITT and ME analysis sets Test of Cure (TOC) visit, Day 28± 3 days PK/PD relationship between exposure and microbiological response for ATM/AVI±MTZ in the popPK analysis set Test of Cure (TOC) visit, Day 28± 3 days PK/PD relationship between exposure and clinical response for ATM/AVI ± MTZ in the popPK analysis set Test of Cure (TOC) visit, Day 28 ± 3 days
Trial Locations
- Locations (13)
Amrita Institute of Medical Sciences and Research Centre
🇮🇳Ernakulam, KERALA, India
Apollo Hospitals
🇮🇳Chennai, TAMIL NADU, India
Dayanand Medical College & Hospital
🇮🇳Ludhiana, PUNJAB, India
Deenanath Mangeshkar Hospital and Research Centre
🇮🇳Pune, MAHARASHTRA, India
Government Medical College
🇮🇳Kozhikode, KERALA, India
JSS Hospital
🇮🇳Mysore, KARNATAKA, India
King george Hospital
🇮🇳Visakhapatnam, ANDHRA PRADESH, India
King George’s Medical University
🇮🇳Lucknow, UTTAR PRADESH, India
M S Ramaiah Medical College and Hospitals
🇮🇳Bangalore, KARNATAKA, India
Manipal University, Kasturba Hospital
🇮🇳Udupi, KARNATAKA, India
Scroll for more (3 remaining)Amrita Institute of Medical Sciences and Research Centre🇮🇳Ernakulam, KERALA, IndiaDr Binoj Sivasankara Pillai Thankamony AmmaPrincipal investigator91-9447736769binojst@gmail.com