Summary

Eligibility
for people ages 18 years and up (full criteria)
Location
at UCLA
Dates
study started
estimated completion

Description

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 serious infections due to Gram negative bacteria.

Official Title

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-AVI) ±METRONIDAZOLE (MTZ) VERSUS MEROPENEM±COLISTIN (MER±COL) FOR THE TREATMENT OF SERIOUS INFECTIONS DUE TO GRAM NEGATIVE BACTERIA, INCLUDING METALLO-Β-LACTAMASE (MBL) - PRODUCING MULTIDRUG RESISTANT PATHOGENS, FOR WHICH THERE ARE LIMITED OR NO TREATMENT OPTIONS

Details

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-AVI) ± Metronidazole (MTZ) Versus Meropenem±Colistin (MER±COL) For The Treatment Of Serious Infections Due To Gram Negative Bacteria, Including Metallo Β Lactamase (MBL) - Producing Multidrug Resistant Pathogens, For Which There Are Limited Or No Treatment Options

Keywords

Complicated Intra-abdominal Infection Hosptial Acquired Pneumonia Ventilator Associated Pneumonia Gram negative infections Metallo-beta lactamase Multi drug resistant pathogens Infection Communicable Diseases Pneumonia, Ventilator-Associated Intraabdominal Infections Pneumonia ATM-AVI MTZ MER COL Aztreonam-Avibactam ± Metronidazole Meropenem ± Colistin

Eligibility

You can join if…

Open to people ages 18 years and up

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

  1. 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

You CAN'T join if...

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 β-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 ≤15 ml/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 >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
  10. . Patient has a total bilirubin >2 × ULN, unless isolated hyperbilirubinemia is directly related to infectious process or due to known Gilbert's disease
  11. . 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
  12. . Absolute neutrophil count <500/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 hours of diagnosis primary etiology is not likely to be infectious
  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

Locations

  • Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center accepting new patients
    Torrance California 90502 United States
  • Harbor-UCLA Medical Center accepting new patients
    Torrance California 90509 United States

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Pfizer
ID
NCT03329092
Phase
Phase 3
Study Type
Interventional
Last Updated