A Study to Determine the Effect of Aztreonam-Avibactam for the Treatment of Serious Infections Due to Resistant (MBL-producing) Gram Negative Bacteria.
- Conditions
- Health Condition 1: A499- Bacterial infection, unspecifiedHealth Condition 2: K650- Generalized (acute) peritonitisHealth Condition 3: J159- Unspecified bacterial pneumoniaHealth Condition 4: N390- Urinary tract infection, site notspecified
- Registration Number
- CTRI/2019/06/019884
- Lead Sponsor
- Pfizer Limited
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Open to Recruitment
- Sex
- Not specified
- Target Recruitment
- 0
Inclusion Criteria All Subjects
1. Subject must be >=18 years of age.
2. Evidence of a personally signed and dated informed consent document indicating that the
subject or a legally acceptable representative has been informed of all pertinent aspects of the
study.
3. Subjects must have a confirmed diagnosis of serious bacterial infection, specifically cIAI,
HAP/VAP, cUTI, or BSI requiring administration of IV antibacterial therapy.
4. Subjects must have an MBL- positive Gram- negative bacteria (an Enterobacteriaceae and/or
Stenotrophomonas maltophilia for which the imipenem or meropenem MIC is >= 4 μg/mL), that
was isolated from an appropriate specimen obtained within 5 days prior to screening.
5. Female subject of childbearing potential must have a negative serum or urine pregnancy test,
with sensitivity of at least 25 mIU/mL.
6. Subjects who have received appropriate prior systemic antibiotic[s] for a carbapenem nonsusceptible
pathogen must meet the following criteria (Note: antibiotic[s] is considered
appropriate if microbiological susceptibility test results show that all carbapenem non-susceptible
pathogens are susceptible to the systemic antibiotic[s] received):
1. Worsening or lack of improvement of objective symptoms or signs of infection after at least
48 hours of antibacterial therapy Note: Symptomatic subjects (see inclusion criteria 3 and
4) with an isolated causative pathogen that was not susceptible to the prior systemic
therapy are eligible for this trial.
7. Subject must be willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
Additional Inclusion Criteria- cIAI Subjects
1. Subject must have a specimen obtained from an abdominal source during a surgical intervention
within 5 days prior to screening from which a study qualifying pathogen was isolated upon
culture. Surgical intervention includes open laparotomy, percutaneous drainage of an abscess, or
laparoscopic surgery.
2. The subject has at least 1 of the following diagnosed during the surgical intervention:
Cholecystitis with gangrenous rupture or perforation or progression of the infection beyond
the gallbladder wall;
Diverticular disease with perforation or abscess;
Appendiceal perforation or peri-appendiceal abscess;
Acute gastric or duodenal perforations, only if operated on >24 hours after diagnosis;
Traumatic perforation of the intestines, only if operated on >12 hours after diagnosis;
Other secondary peritonitis (not primary/ spontaneous bacterial peritonitis associated with
cirrhosis or chronic ascites);
Intra abdominal abscess (including of the liver and spleen provided that there is extension
beyond the organ with evidence of intra peritoneal involvement).
3. Subject has at least 1 of the following signs / symptoms from each of the following 2 groups:
Group A: Evidence of systemic inflammatory response:
Documented fever (defined as body temperature >=38°C) or hypothermia (with a rectal core
body temperature <=35°C);
Elevated white blood cells (WBC) ( >12000 cells/μL);
Systolic blood pressure (SBP) <90 mmHg or mean arterial pressure (MAP) <70 mmHg, or a
SBP decrease of >40 mmHg;
Exclusion Criteria All Subjects
1. Subject has an Acute Physiology and Chronic Health Evaluation (APACHE) II score >30.
2. Subjects unlikely to respond to up to 14 days of study treatment.
3. History of serious allergic reaction (anaphylaxis, angioedema, bronchospasm, hypersensitivity) to any systemic antibacterial allowed per protocol.
4. Subject has previously been treated with ATM-AVI Subject with known Clostridium difficile associated diarrhea.
5. Subjects with perinephric infection.
6. Colonization with an MBL-producing Gram-negative bacteria without signs or symptoms.
7. Estimated CrCL <=15 mL/min or anticipated requirement for dialysis during the study.
8. Hepatic disease as indicated by ALT or AST >3 x ULN at Screening. Exception: AST and/or ALT up to 5 x ULN if these elevations are acute and directly related to the infectious process.
9. Bilirubin greater than 2 X ULN, unless related to the acute infection or due to known Gilberts disease.
10. Alkaline phosphatase (ALP) >3 x ULN. Exception: up to <5 x ULN if this value is acute and related to the infectious process.
11. Absolute neutrophil count <500/mm3.
Additional Exclusion Criteria - cIAI Subjects
1. Subject has infections limited to the hollow viscous, such as simple cholecystitis, gangrenous cholecystitis without rupture, and simple appendicitis, or has acute suppurative cholangitis, infected necrotizing pancreatitis, or pancreatic abscess.
2. Subject has abdominal wall abscess or small bowel obstruction without perforation or ischemic bowel without perforation.
3. Subject has a cIAI managed by staged abdominal repair (STAR), or open abdomen technique, or
marsupialization. This criterion is intended to exclude subjects in whom the abdomen is left open,particularly those for whom re operation is planned.
4. Subject who has prior liver, pancreas or small bowel transplant.
Additional Exclusion Criteria - HAP/VAP Subjects 1. APACHE II score <10. 2. Subjects with lung
abscess, pleural empyema, or post obstructive pneumonia. 3. Subject is a recipient of a lung or heart transplant. 4. Subjects with myasthenia gravis.
Additional exclusion criteria - cUTI Subjects
1. Subjects with suspected or confirmed complete obstruction of any portion of the urinary tract,
perinephric or intrarenal abscess, or prostatitis, or history of any illness that, in the opinion of the investigator, may confound the results of the study or pose additional risk in administering the study therapy to the subject.
2. Subjects with renal transplantation.
3. Subjects with a permanent urinary diversion (eg, with ileal loops, cutaneous ureterostomy or
vesicoureteral reflux).
4. Subjects who are likely to receive ongoing antibacterial drug prophylaxis after treatment of cUTI
(eg, subjects with vesico-ureteric reflux).
5. Any recent history of trauma to the pelvis or urinary tract.
6. Subjects with uncomplicated urinary tract infections (generally female subjects with urinary frequency, urgency, or pain or discomfort without systemic symptoms or signs of infection).
Additional exclusion criteria - BSI Subjects
1. Subject has a prosthetic cardiac valve or synthetic endovascular graft. 2. Subject has a suspected or
documented medical condition with well
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method