Complicated Urinary Tract InfectionPhase 3Integral-2NCT05905055
P3 Study to Assess Efficacy and Safety of Cefepime/Nacubactam and Aztreonam/Nacubactam Versus Best Available Therapy for Adults With Infection Due to Carbapenem Resistant Enterobacterales
A Phase 3 study testing co-administration of cefepime and nacubactam, co-administration of aztreonam and nacubactam and BAT in people with Complicated Urinary Tract Infection and Acute Pyelonephritis, run by Meiji Seika Pharma Co., Ltd. at 54 sites in 14 countries.
Trial summary
This study is a multi-center, randomized, single-blind, parallel-group study to assess the efficacy and safety, when nacubactam is coadministered with cefepime or aztreonam, compared with best available therapy (BAT), in the treatment of patients with cUTI, AP, HABP, VABP, and cIAI, due to Carbapenem Resistant… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Complicated Urinary Tract Infection, Acute Pyelonephritis, Hospital-acquired Bacterial Pneumonia
- What is being tested?
- co-administration of cefepime and nacubactam, co-administration of aztreonam and nacubactam and BAT
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 126 participants
- Where
- 54 sitesin 14 countries
- Study dates
- 22 Sep 2023to 1 Sep 2025
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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;
- Weight at most 140 kg;
- The following criteria must be satisfied:
- 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.
Who cannot join
- 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)
- 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
- Has only a Gram-positive organism pathogen isolated from study-qualifying culture;
Trial locations and contacts
54 sites in 14 countries.
54 sites in 14 countries
China14 sites
Meiji Research Site
Changsha
Meiji Research Site
Chongqing
Meiji Research Site
Fuyang
Meiji Research Site
Guangzhou
Meiji Research Site
Hangzhou
Meiji Research Site
Hefei
Meiji Research Site
Nanjing
Meiji Research Site
Nanning
Meiji Research Site
Quanzhou
Meiji Research Site
Shanghai
Meiji Research Site
Shenzhen
Meiji Research Site
Shijiazhuang
Meiji Research Site
Wuxi
Meiji Research Site
Xuzhou
Japan8 sites
Meiji Research Site
Hiroshima
Meiji Research Site
Kanazawa
Meiji Research Site
Nagasaki
Meiji Research Site
Nankoku, Kochi
Meiji Research Site
Nankoku
Meiji Research Site
Ōta-ku
Meiji Research Site
Shinjuku-ku
Meiji Research Site
Toyoake
Turkey (Türkiye)5 sites
Meiji Research Site
Ankara
Meiji Research Site
Eskişehir
Meiji Research Site
Istanbul
Meiji Research Site
İzmit
Meiji Research Site
Trabzon
France4 sites
Meiji Research Site
Limoges
Meiji Research Site
Nîmes
Meiji Research Site
Paris
Meiji Research Site
Strasbourg
Latvia4 sites
Meiji Research Site
Daugavpils
Meiji Research Site
Liepāja
Meiji Research Site
Riga
Meiji Research Site
Valmiera
Georgia3 sites
Meiji Research Site
Kutaisi
Meiji Research Site
Tbilisi
Meiji Research Site
Zestaponi
Israel3 sites
Meiji Research Site
Be’er Ya‘aqov
Meiji Research Site
Ramat Gan
Meiji Research Site
Tel Aviv
Taiwan3 sites
Meiji Research Site
Kaohsiung City
Meiji Research Site
Taichung
Meiji Research Site
Taipei
Thailand3 sites
Meiji Research Site
Bangkok
Meiji Research Site
Chiang Mai
Meiji Research Site
Khon Kaen
About this study
Official title: 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 a multi-center, randomized, single-blind, parallel-group study to assess the efficacy and safety, when nacubactam is coadministered with cefepime or aztreonam, compared with best available therapy (BAT), in the treatment of patients with cUTI, AP, HABP, VABP, and cIAI, due to Carbapenem Resistant Enterobacterales.
- Conditions
- Complicated Urinary Tract Infection, Acute Pyelonephritis, Hospital-acquired Bacterial Pneumonia, Ventilator-associated Bacterial Pneumonia, Complicated Intra-abdominal Infection
- Being tested
- co-administration of cefepime and nacubactam, co-administration of aztreonam and nacubactam, BAT
- Keywords
- nacubactam, OP0595, Integral-2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
co-administration of cefepime and nacubactamDrug
2 g cefepime and 1 g nacubactam every 8 hours for at least 5 days and up to 14 days via IV infusion over a period of 60 minutes
co-administration of aztreonam and nacubactamDrug
2 g aztreonam and 1 g nacubactam every 8 hours for at least 5 days and up to 14 days via IV infusion over a period of 60 minutes
BATDrug
Dosage of BAT will be based per site's standard of care
| Study group | Role | What they receive |
|---|---|---|
| co-administration of cefepime and nacubactam | Experimental | co-administration of 2 g cefepime and 1 g nacubactam q8h (60 min. infusion) Receives: Drug: co-administration of cefepime and nacubactam |
| co-administration of aztreonam and nacubactam | Experimental | co-administration of 2 g aztreonam and 1g nacubactam q8h (60 min. infusion) Receives: Drug: co-administration of aztreonam and nacubactam |
| BAT | Active comparator | Best Available Therapy Receives: Drug: BAT |
What is being measured
The primary outcome is the main question the study is designed to answer.
The primary efficacy endpoint is the proportion of patients with overall treatment success at TOC across all infection types (ie, cUTI, AP, HABP, VABP, and cIAI), which is a composite endpoint derived from the efficacy outcomes of each infection type.
For cUTI and AP, the composite clinical outcome of cure and the microbiological outcome of eradication are defined as the outcome of cure.
For HABP and VABP, the clinical success is defined as the outcome of cure. For cIAI, the clincal success is defined as the outcome of cure.
Measured: TOC (Test of Cure visit): 7 [±2] days after EOT (end of treatment) [Day 10 to 23 after the start of treatment]
Secondary outcomes (21)
The proportion of patients with overall treatment outcome of success across all infection types
Overall treatment success was defined according to infection type. For cUTI/AP, it was defined as the composite of clinical outcome of cure and microbiological outcome of eradication.
For HABP/VABP and cIAI, it was defined as clinical outcome of cure alone.
Measured: Outcome measurements were assessed at various visits: EA (Early Assessment): Day 3 to 5 days, EOT: (End of Treatment): Day 5 to Day 14, FUP (Follow-Up visit): Day 17 to Day 30
The proportion of patients with a clinical outcome of cure per type of resistance
Assessment of clinical outcome was based on the Investigator's evaluation of the patient's clinical signs and symptoms, with cure defined as the complete resolution (or return to premorbid state) of the baseline signs and symptoms present at screening, such that no further antimicrobial therapy is warranted.
For this endpoint, results were summarized per type of resistance.
Measured: TOC (Test of Cure visit):7 [±2] days after EOT [Day 10 to 23]
The proportion of patients with a microbiological outcome of eradication per type of pathogen and per type of resistance
For cUTI/AP, microbiological outcome was determined programmatically based on quantitative microbiological urine cultures, with eradication defined as the pathogen found at screening with 10^5 CFU/ml or more reduced to less than 10^3 CFU/ml.
For HABP/VABP and cIAI, eradication was defined as the absence of the baseline Gram-negative pathogen(s) on repeat culture, or presumed eradication, which is no culture was done and the patient meets the clinical criteria for clinical cure.
The results of subgroup analyses for only the three most frequent pathogens were shown because there were a large number of pathogen types, most of which were rare and sparsely represented in the dataset.
Measured: TOC (Test of Cure visit):7 [±2] days after EOT [Day 10 to 23]
The all-cause mortality rate at Day 28 by each infection type (ie, cUTI/AP, HABP/VABP, or cIAI) and across all infection types
The all-cause mortality rate at Day 28 was calculated as the percentage of participants who experienced mortality regardless of the cause at or before Day 28.
Measured: Day 28 (+ 2days)
The proportion of patients with a clinical outcome of cure by each infection type (ie, cUTI/AP, HABP/VABP, or cIAI) and across all infection types
Assessment of clinical outcome was based on the Investigator's evaluation of the patient's clinical signs and symptoms, with cure defined as the complete resolution (or return to premorbid state) of the baseline signs and symptoms present at screening, such that no further antimicrobial therapy is warranted.
Results were summarized by each infection type (ie, cUTI/AP, HABP/VABP, or cIAI) and across all infection types.
Measured: TOC (Test of Cure visit):7 [±2] days after EOT [Day 10 to 23]
The proportion of patients with a microbiological outcome of eradication (including presumed eradication) by each infection type (ie, cUTI/AP, HABP/VABP, or cIAI) and across all infection types
For cUTI/AP, microbiological outcome was determined programmatically based on quantitative microbiological urine cultures, with eradication defined as the pathogen found at screening with 10^5 CFU/ml or more reduced to less than 10^3 CFU/ml.
For HABP, VABP, and cIAI, eradication was defined as the absence of the baseline Gram-negative pathogen(s) on repeat culture, or presumed eradication, which is no culture was done and the patient meets the clinical criteria for clinical cure.
Results were summarized by each infection type (ie, cUTI/AP, HABP/VABP, or cIAI) and across all infection types.
Measured: TOC (Test of Cure visit):7 [±2] days after EOT [Day 10 to 23]
The proportion of patients with composite clinical and microbiological success for cUTI/AP patients
Composite clinical and microbiological success is defined as the composite clinical outcome of cure and the microbiological outcome of eradication.
Assessment of clinical outcome was based on Investigator's evaluation of the patient's clinical signs and symptoms, with cure defined as the complete resolution (or return to premorbid state) of the baseline signs and symptoms of cUTI or AP that were present at screening, such that no further antimicrobial therapy is warranted.
Microbiological outcome was determined programmatically based on quantitative microbiological urine cultures, with eradication defined as the pathogen found at screening with 10^5 CFU/ml or more reduced to less than 10^3 CFU/ml.
Measured: TOC (Test of Cure visit):7 [±2] days after EOT [Day 10 to 23]
The proportion of patients with composite clinical outcome of recurrence and/or microbiological outcome of recurrence at the FUP for cUTI/AP patients
Composite clinical and microbiological success is defined as the composite clinical outcome of cure and the microbiological outcome of eradication.
Assessment of clinical outcome was based on Investigator's evaluation of the patient's clinical signs and symptoms, with cure defined as the complete resolution (or return to premorbid state) of the baseline signs and symptoms of cUTI or AP that were present at screening, such that no further antimicrobial therapy is warranted.
Microbiological outcome was determined programmatically based on quantitative microbiological urine cultures, with eradication defined as the pathogen found at screening with 10^5 CFU/ml or more reduced to less than 10^3 CFU/ml.
Measured: FUP(Follow-Up visit):14 [±2] days after EOT [Day 17 to Day 30]
Total ventilator days measured from time of randomization to EOT for HABP/VABP patients
Total ventilator days are defined as number of days from the date of randomization to the date at which the ventilator is removed or date of end of treatment, whichever is earlier.
Measured: EOT (End of Treatment): [Day 5 to Day 14]
Change in the partial pressure of oxygen to FiO2 ratio from baseline to EOT for HABP/VABP patients
The partial pressure oxygen to fraction of inspired oxygen ratio at baseline and EOT and change from baseline is summarized by treatment group.
Measured: EOT (End of Treatment): [Day 5 to Day 14]
Time (days) to extubation in patients who are on the ventilator at baseline for HABP/VABP patients
Time to extubation was defined as number of days from the date of the first dose of study drug to the last date at which the ventilator was removed. Kaplan-Meier estimates were used for the analysis of time to extubation for each treatment group, and hazard ratios along with 95% CI was used to analyze time to extubation differences between treatment groups. Patients who were on the ventilator at baseline but discontinued from the study without extubation were considered censored.
Measured: Up to EOT (End of Treatment): [Day 5 to Day 14]
The proportion of patients with clinical outcome of recurrence at the FUP for HABP/VABP patients
Clinical Outcome of Recurrence is defined as the reappearance of baseline clinical signs and symptoms at the Follow-up (FUP) visit after a prior assessment of cure.
Measured: FUP(Follow-Up visit):14 [±2] days after EOT [Day 17 to Day 30]
The proportion of patients with clinical outcome of recurrence at the FUP for cIAI patients
Clinical Outcome of Recurrence is defined as the reappearance of baseline clinical signs and symptoms at the Follow-up (FUP) visit after a prior assessment of cure.
Measured: FUP(Follow-Up visit):14 [±2] days after EOT [Day 17 to Day 30]
The all-cause mortality rate at Day 28 for secondary bacteremia patients
The all-cause mortality rate at Day 28 was calculated as the percentage of participants who experienced mortality regardless of the cause at or before Day 28.
Measured: Day 28 (+ 2days)
The proportion of patients with overall treatment success across all infection types at TOC for secondary bacteremia patients
Patients with isolation of a gram-negative bacteria from at least 1 blood culture at baseline and this isolated pathogen is also identified from the site of infection and signs and symptoms of secondary bacteremia were determined programmatically as secondary bacteremia.
Overall treatment success was defined according to infection type. For cUTI/AP, it was defined as the composite of clinical outcome of cure and microbiological outcome of eradication.
For HABP, VABP, and cIAI, it was defined as clinical outcome of cure alone.
Measured: TOC (Test of Cure visit):7 [±2] days after EOT [Day 10 to 23]
The proportion of patients with a clinical outcome of cure across all infection types at TOC for secondary bacteremia patients
Patients with isolation of a gram-negative bacteria from at least 1 blood culture at baseline and this isolated pathogen is also identified from the site of infection and signs and symptoms of secondary bacteremia were determined programmatically as secondary bacteremia.
Assessment of clinical outcome was based on the Investigator's evaluation of the patient's clinical signs and symptoms, with cure defined as the complete resolution (or return to premorbid state) of the baseline signs and symptoms present at screening, such that no further antimicrobial therapy is warranted.
Measured: TOC (Test of Cure visit):7 [±2] days after EOT [Day 10 to 23]
The proportion of patients with a microbiological outcome of eradication across all infection types at TOC for secondary bacteremia patients
Patients with isolation of a gram-negative bacteria from at least 1 blood culture at baseline and this isolated pathogen is also identified from the site of infection and signs and symptoms of secondary bacteremia were determined programmatically as secondary bacteremia.
Microbiological outcome will be determined programmatically based on blood cultures, with eradication defined as the pathogen found at screening is negative in blood culture.
Measured: TOC (Test of Cure visit):7 [±2] days after EOT [Day 10 to 23]
The proportion of patients with a clinical outcome of cure from secondary bacteremia at TOC for secondary bacteremia patients
Patients with isolation of a gram-negative bacteria from at least 1 blood culture at baseline and this isolated pathogen is also identified from the site of infection and signs and symptoms of secondary bacteremia were determined programmatically as secondary bacteremia.
Clinical outcome of cure from secondary bacteremia is defined as complete resolution or significant improvement of the baseline signs and symptoms of secondary bacteremia.
Measured: TOC (Test of Cure visit):7 [±2] days after EOT [Day 10 to 23]
The proportion of patients with a microbiological outcome of eradication from secondary bacteremia at TOC for secondary bacteremia patients
Patients with isolation of a gram-negative bacteria from at least 1 blood culture at baseline and this isolated pathogen is also identified from the site of infection and signs and symptoms of secondary bacteremia were determined programmatically as secondary bacteremia.
Microbiological outcome will be determined programmatically based on blood cultures, with eradication defined as the pathogen found at screening is negative in blood culture.
Measured: TOC (Test of Cure visit):7 [±2] days after EOT [Day 10 to 23]
The proportion of patients who are free from secondary bacteremia at TOC for secondary bacteremia patients
Patients with isolation of a gram-negative bacteria from at least 1 blood culture at baseline and this isolated pathogen is also identified from the site of infection and signs and symptoms of secondary bacteremia were determined programmatically as secondary bacteremia.
Both clinical outcome and microbiological outcome were evaluated in patients with secondary bacteremia.
Assessment of clinical outcome was based on signs and symptoms, with cure defined as complete resolution or significant improvement of the baseline signs and symptoms of secondary bacteremia. Microbiological outcome will be determined programmatically based on blood cultures, with eradication defined as the pathogen found at screening is negative in blood culture.
Measured: TOC (Test of Cure visit):7 [±2] days after EOT [Day 10 to 23]
The proportion of patients free from the definition of secondary bacteremia and a clinical outcome of cure across all infection types and a microbiological outcome of eradication from all infection types at TOC for secondary bacteremia patients
Patients with isolation of a gram-negative bacteria from at least 1 blood culture at baseline and this isolated pathogen is also identified from the site of infection and signs and symptoms of secondary bacteremia were determined programmatically as secondary bacteremia. For assessment of cUTI/AP, HABP/VABP, cIAI is done by the same way as clinical outcome and microbiological outcome. For secondary bacteremia, assessment of clinical outcome was based on signs and symptoms, with cure defined as complete resolution or significant improvement of the baseline signs and symptoms of secondary bacteremia. Microbiological outcome will be determined programmatically based on blood cultures, with eradication defined as the pathogen found at screening is negative in blood culture.
Measured: TOC (Test of Cure visit):7 [±2] days after EOT [Day 10 to 23]
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jun 2023
- Study start22 Sep 2023
- Primary completion1 Sep 2025
- Study completion1 Sep 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Complicated Urinary Tract InfectionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 126 participants (actual)
Sponsor and investigators
- Lead sponsor
- Meiji Seika Pharma Co., Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05905055
- Sponsor's protocol ID
- OP0595-6
- Acronym
- Integral-2
- Status last verified
- Apr 2026
- First submitted
- 2 Mar 2023
- Last updated
- 13 Apr 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT05905055
- Acronym / sponsor ID
- Integral-2 / OP0595-6
- Conditions
- Complicated Urinary Tract Infection, Acute Pyelonephritis, Hospital-acquired Bacterial Pneumonia, Ventilator-associated Bacterial Pneumonia, Complicated Intra-abdominal Infection
- Keywords
- nacubactam, OP0595, Integral-2
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 126 participants (actual)
- Lead sponsor
- Meiji Seika Pharma Co., Ltd.Industry (pharma, biotech, devices)
- Study start
- 22 Sep 2023 (actual)
- Primary completion
- 1 Sep 2025 (actual)
- Study completion
- 1 Sep 2025 (actual)
- First posted
- 15 Jun 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is a multi-center, randomized, single-blind, parallel-group study to assess the efficacy and safety, when nacubactam is coadministered with cefepime or aztreonam, compared with best available therapy (BAT), in the treatment of patients with cUTI, AP, HABP, VABP, and cIAI, due to Carbapenem Resistant Enterobacterales.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| co-administration of cefepime and nacubactam | Experimental | Drug: co-administration of cefepime and nacubactamco-administration of 2 g cefepime and 1 g nacubactam q8h (60 min. infusion) |
| co-administration of aztreonam and nacubactam | Experimental | Drug: co-administration of aztreonam and nacubactamco-administration of 2 g aztreonam and 1g nacubactam q8h (60 min. infusion) |
| BAT | Active comparator | Drug: BATBest Available Therapy |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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;
- Weight at most 140 kg;
- The following criteria must be satisfied:
Key exclusion criteria (3 listed)
- 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)
- 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
- Has only a Gram-positive organism pathogen isolated from study-qualifying culture;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| co-administration of cefepime and nacubactam2 g cefepime and 1 g nacubactam every 8 hours for at least 5 days and up to 14 days via IV infusion over a period of 60 minutes | Drug | co-administration of cefepime and nacubactam |
| co-administration of aztreonam and nacubactam2 g aztreonam and 1 g nacubactam every 8 hours for at least 5 days and up to 14 days via IV infusion over a period of 60 minutes | Drug | co-administration of aztreonam and nacubactam |
| BATDosage of BAT will be based per site's standard of care | Drug | BAT |
Primary outcome
The primary efficacy endpoint is the proportion of patients with overall treatment success at TOC across all infection types (ie, cUTI, AP, HABP, VABP, and cIAI), which is a composite endpoint derived from the efficacy outcomes of each infection type.
Time frame: TOC (Test of Cure visit): 7 [±2] days after EOT (end of treatment) [Day 10 to 23 after the start of treatment]
For cUTI and AP, the composite clinical outcome of cure and the microbiological outcome of eradication are defined as the outcome of cure. For HABP and VABP, the clinical success is defined as the outcome of cure. For cIAI, the clincal success is defined as the outcome of cure.
21 secondary outcomes
The proportion of patients with overall treatment outcome of success across all infection types
Time frame: Outcome measurements were assessed at various visits: EA (Early Assessment): Day 3 to 5 days, EOT: (End of Treatment): Day 5 to Day 14, FUP (Follow-Up visit): Day 17 to Day 30
The proportion of patients with a clinical outcome of cure per type of resistance
Time frame: TOC (Test of Cure visit):7 [±2] days after EOT [Day 10 to 23]
The proportion of patients with a microbiological outcome of eradication per type of pathogen and per type of resistance
Time frame: TOC (Test of Cure visit):7 [±2] days after EOT [Day 10 to 23]
The all-cause mortality rate at Day 28 by each infection type (ie, cUTI/AP, HABP/VABP, or cIAI) and across all infection types
Time frame: Day 28 (+ 2days)
The proportion of patients with a clinical outcome of cure by each infection type (ie, cUTI/AP, HABP/VABP, or cIAI) and across all infection types
Time frame: TOC (Test of Cure visit):7 [±2] days after EOT [Day 10 to 23]
The proportion of patients with a microbiological outcome of eradication (including presumed eradication) by each infection type (ie, cUTI/AP, HABP/VABP, or cIAI) and across all infection types
Time frame: TOC (Test of Cure visit):7 [±2] days after EOT [Day 10 to 23]
The proportion of patients with composite clinical and microbiological success for cUTI/AP patients
Time frame: TOC (Test of Cure visit):7 [±2] days after EOT [Day 10 to 23]
The proportion of patients with composite clinical outcome of recurrence and/or microbiological outcome of recurrence at the FUP for cUTI/AP patients
Time frame: FUP(Follow-Up visit):14 [±2] days after EOT [Day 17 to Day 30]
Total ventilator days measured from time of randomization to EOT for HABP/VABP patients
Time frame: EOT (End of Treatment): [Day 5 to Day 14]
Change in the partial pressure of oxygen to FiO2 ratio from baseline to EOT for HABP/VABP patients
Time frame: EOT (End of Treatment): [Day 5 to Day 14]
Time (days) to extubation in patients who are on the ventilator at baseline for HABP/VABP patients
Time frame: Up to EOT (End of Treatment): [Day 5 to Day 14]
The proportion of patients with clinical outcome of recurrence at the FUP for HABP/VABP patients
Time frame: FUP(Follow-Up visit):14 [±2] days after EOT [Day 17 to Day 30]
The proportion of patients with clinical outcome of recurrence at the FUP for cIAI patients
Time frame: FUP(Follow-Up visit):14 [±2] days after EOT [Day 17 to Day 30]
The all-cause mortality rate at Day 28 for secondary bacteremia patients
Time frame: Day 28 (+ 2days)
The proportion of patients with overall treatment success across all infection types at TOC for secondary bacteremia patients
Time frame: TOC (Test of Cure visit):7 [±2] days after EOT [Day 10 to 23]
The proportion of patients with a clinical outcome of cure across all infection types at TOC for secondary bacteremia patients
Time frame: TOC (Test of Cure visit):7 [±2] days after EOT [Day 10 to 23]
The proportion of patients with a microbiological outcome of eradication across all infection types at TOC for secondary bacteremia patients
Time frame: TOC (Test of Cure visit):7 [±2] days after EOT [Day 10 to 23]
The proportion of patients with a clinical outcome of cure from secondary bacteremia at TOC for secondary bacteremia patients
Time frame: TOC (Test of Cure visit):7 [±2] days after EOT [Day 10 to 23]
The proportion of patients with a microbiological outcome of eradication from secondary bacteremia at TOC for secondary bacteremia patients
Time frame: TOC (Test of Cure visit):7 [±2] days after EOT [Day 10 to 23]
The proportion of patients who are free from secondary bacteremia at TOC for secondary bacteremia patients
Time frame: TOC (Test of Cure visit):7 [±2] days after EOT [Day 10 to 23]
The proportion of patients free from the definition of secondary bacteremia and a clinical outcome of cure across all infection types and a microbiological outcome of eradication from all infection types at TOC for secondary bacteremia patients
Time frame: TOC (Test of Cure visit):7 [±2] days after EOT [Day 10 to 23]
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Apr 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
54 sites in 14 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing co-administration of cefepime and nacubactam, co-administration of aztreonam and nacubactam and BAT in people with Complicated Urinary Tract Infection and Acute Pyelonephritis, run by Meiji Seika Pharma Co., Ltd. at 54 sites in 14 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 54 sites in China, Japan, Turkey (Türkiye), France, Latvia and 9 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The primary efficacy endpoint is the proportion of patients with overall treatment success at TOC across all infection types (ie, cUTI, AP, HABP, VABP, and cIAI), which is a composite endpoint derived from the efficacy outcomes of each infection type. (time frame: TOC (Test of Cure visit): 7 [±2] days after EOT (end of treatment) [Day 10 to 23 after the start of treatment]). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Apr 2026.