Assessing new treatments for infections caused by resistant bacteria

A Phase 3, Multi-Center, Randomized, Single-Blind Study to Assess the Efficacy and Safety of Cefepime/Nacubactam and Aztreonam/Nacubactam Versus Best Available Therapy in Adults With Complicated Urinary Tract Infection, Acute Uncomplicated Pyelonephritis, Hospital-Acquired Bacterial Pneumonia, Ventilator Associated Bacterial Pneumonia, and Complicated Intra-Abdominal Infection Due to Carbapenem Resistant Enterobacterales

This study is testing two new combinations of antibiotics to see if they can help adults with serious infections caused by tough-to-treat bacteria.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 150 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Meiji Seika Pharma Co., Ltd. (Industry-sponsored)
• Locations: 1 site (Nankoku, Kochi)
• Trial ID: NCT05905055 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the efficacy and safety of cefepime and nacubactam, as well as aztreonam and nacubactam, in comparison to the best available therapy for adults suffering from infections caused by carbapenem-resistant Enterobacterales. It is a multi-center, randomized, single-blind, parallel-group study that aims to determine the effectiveness of these combinations in treating complicated urinary tract infections, acute pyelonephritis, and various types of pneumonia. Participants will be hospitalized throughout the treatment period to ensure proper monitoring and care.

Who should consider this trial

Good fit: Ideal candidates for this study are adults aged 18 and older with confirmed infections due to carbapenem-resistant Enterobacterales.

Not a fit: Patients who have already received effective antimicrobial therapy for their infection within the specified time frame may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide new effective treatment options for patients with difficult-to-treat infections caused by resistant bacteria.

How similar studies have performed: Other studies have explored similar combinations of antibiotics for resistant infections, showing promising results, but this specific combination is relatively novel.

Eligibility criteria

Inclusion Criteria:

1. Male or female patients at least 18 years of age (or age of legal consent, whichever is older) at the time of obtaining informed consent and who can be hospitalized throughout the Treatment Period;
2. Weight at most 140 kg;
3. The following criteria must be satisfied:

   a. For known CRE infection, meets either of the following (i or ii): i. Has a known CRE infection, alone or as a single isolate of a polymicrobial infection, based on evidence from CRE culture, susceptibility testing, and possible carbapenemase phenotypic testing (or possible molecular testing) within 72 hours (or 96 hours for cIAI) prior to the first dose of study drug; AND Has received no more than 24 hours of an antimicrobial agent to which the known CRE is known to be susceptible within 72 hours (or 96 hours for cIAI) prior to the first dose of study drug; OR ii. Has a known CRE infection, alone or as a single isolate of a polymicrobial infection, based on evidence from CRE culture, susceptibility testing, and possible carbapenemase phenotypic testing (or possible molecular testing) within 72 hours (or 96 hours for cIAI) prior to the first dose of study drug; AND Has documented clinical evidence of failure (ie, clinical deterioration or failure to improve) after at least 48 hours of treatment with an antimicrobial agent to which the known CRE is known to be susceptible within 72 hours (or 96 hours for cIAI) prior to the first dose of study drug; b. For suspected CRE infection, meets the following (i or ii): i. Has a suspected CRE infection, alone or as a single isolate of a polymicrobial infection, based on evidence which may be determined within 90 days prior to the first dose of study drug through rapid diagnostic tests, active surveillance cultures, other documentation of CRE colonization, or prior infection due to a CRE pathogen; AND Has received no more than 24 hours of empiric antimicrobial therapy for Gram negative organisms within 72 hours (or 96 hours for cIAI) prior to the first dose of study drug； ii. Has a suspected CRE infection, alone or as a single isolate of a polymicrobial infection, based on evidence which may be determined within 90 days prior to the first dose of study drug through rapid diagnostic tests, active surveillance cultures, other documentation of CRE colonization, or prior infection due to a CRE pathogen; AND Has documented clinical evidence of failure (ie, clinical deterioration or failure to improve) after at least 48 hours of treatment with empiric antimicrobial therapy for Gram-negative organisms within 72 hours (or 96 hours for cIAI) prior to the first dose of study drug; Note: CRE is defined as Enterobacterales by susceptibility data of MIC at least 2 microg/mL to imipenem or meropenem OR imipenem or meropenem disk diffusion (zone diameter \< 22 mm). If MIC or disk diffusion data are not available in the local laboratory or before the availability of MIC or disk diffusion results, each site can use other methods and criteria in the institution (eg, phenotypic or molecular testing) as the initial evidence of CRE for enrollment. In any case, pathogen identification and susceptibility testing performed at the central laboratory will be used to determine CRE in the final study analysis.

Exclusion Criteria:

1. Has a history of serious allergy, hypersensitivity (eg, anaphylaxis), or any serious allergic reaction to carbapenems, cephems, penicillins, other beta-lactam antibiotics, or any BLIs (eg, tazobactam, sulbactam, or clavulanic acid)
2. Has known or suspected single or concurrent infection with Acinetobacter spp., metallo-β-lactamase (MBL) producing Pseudomonas aeruginosa, or other organisms that are not adequately covered by the study drug (eg, concurrent viral, mycobacterial, or fungal infection) and need to be managed with other anti-infectives; Note: Patients with qualifying Gram-negative pathogen co-infected with a Gram-positive pathogen may be administered narrow spectrum, open-label glycopeptide (eg, vancomycin), oxazolidinone (eg, linezolid), or daptomycin concomitantly with the study drug at the discretion of the Investigator. Patients with cIAI may receive metronidazole in addition to cefepime/nacubactam, aztreonam/nacubactam, or as part of BAT if anaerobic coverage is deemed necessary
3. Has only a Gram-positive organism pathogen isolated from study-qualifying culture;

Where this trial is running

Nankoku, Kochi

• Meiji Research Site — Nankoku, Kochi, Japan (Recruiting)

Study contacts

• Study coordinator: Keisuke Suwada

Conditions Complicated Urinary Tract Infection; Acute Pyelonephritis; Hospital-acquired Bacterial Pneumonia; Ventilator-associated Bacterial Pneumonia; Complicated Intra-abdominal Infection