A Study to Determine the Effect of Aztreonam-Avibactam Versus Meropenem for the Treatment of Serious Infections Due to Gram Negative Bacteria.
- Conditions
- Health Condition 1: K650- Generalized (acute) peritonitisHealth Condition 2: J159- Unspecified bacterial pneumonia
- Registration Number
- CTRI/2018/09/015762
- Lead Sponsor
- Pfizer Limited
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 27
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
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.
11. 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.
13. Pregnant or breastfeeding or if of child bearing potential, not using a medically accepted effective method of birth control.
14. 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. Prior liver, pancreas or small-bowel transplant
4. 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 setsTimepoint: Test of Cure (TOC) visit, Day 28 ± 3 days
- Secondary Outcome Measures
Name Time Method