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Complicated Urinary Tract InfectionPhase 3Integral-1NCT05887908

Efficacy and Safety of Cefepime/Nacubactam or Aztreonam/Nacubactam Compared to Imipenem/Cilastatin in Subjects With Complicated Urinary Tract Infections or Acute Uncomplicated Pyelonephritis

A Phase 3 study testing co-administration of cefepime and nacubactam, co-administration of aztreonam and nacubactam and imipenem/cilastatin in people with Complicated Urinary Tract Infection and Acute Pyelonephritis, run by Meiji Seika Pharma Co., Ltd. at 61 sites in 9 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

Phase 3 study to evaluate the efficacy and safety of cefepime/nacubactam or aztreonam/nacubactam compared to imipenem/cilastatin in the treatment of complicated urinary tract infections (cUTI) or acute uncomplicated pyelonephritis (AP). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
co-administration of cefepime and nacubactam, co-administration of aztreonam and nacubactam and imipenem/cilastatin
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
614 participants
Where
61 sitesin 9 countries
Study dates
23 May 2023to 26 Nov 2024
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 least18 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;
  • Expectation, in the opinion of the Investigator, that the patient's cUTI or AP will require treatment with at least 5 days of IV antibiotics;

Who cannot join

  • Has a known imipenem- and/or meropenem-resistant Gram-negative uropathogen (at least 10^5 CFU/mL), isolated from study-qualifying urine culture; Note: If after randomization the susceptibility testing indicates resistance to imipenem and/or meropenem, the patient may remain on the study drug at the Investigator's discretion.
  • Has known or suspected single or concurrent infection with Acinetobacter spp. or other organisms that are not adequately covered by the study drug (eg, concurrent viral, mycobacterial, or fungal infection) and needs to be managed with other anti-infectives; Note: Patients with qualifying pathogen coinfected 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 Investigator's discretion.
  • Has only a known Gram-positive primary uropathogen (at least 10^5 CFU/mL), isolated from study qualifying urine culture;

Trial locations and contacts

61 sites in 9 countries.

61 sites in 9 countries

Japan20 sites
  • Meiji Research Site

    Fukuyama

  • Meiji Research Site

    Gifu

  • Meiji Research Site

    Ibaraki-Town, Higashiibaraki-County

  • Meiji Research Site

    Iwakuni

  • Meiji Research Site

    Kanazawa

  • Meiji Research Site

    Kawachi-Nagano

  • Meiji Research Site

    Kofu

  • Meiji Research Site

    Kumamoto

  • Meiji Research Site

    Matsumoto

  • Meiji Research Site

    Mizumaki-Town, Onga-County

  • Meiji Research Site

    Nagasaki

  • Meiji Research Site

    Nankoku

  • Meiji Research Site

    Ōita

  • Meiji Research Site

    Ōtake

  • Meiji Research Site

    Sagamihara

  • Meiji Research Site

    Sapporo

  • Meiji Research Site

    Shinjuku-ku

  • Meiji Research Site

    Toyota

  • Meiji Research Site

    Ueda

  • Meiji Research Site

    Yokohama

Other trials in Japan

China19 sites
  • Meiji Research Site

    Beijing

  • Meiji Research Site

    Changchun

  • Meiji Research Site

    Chongqing

  • Meiji Research Site

    Fuyang

  • Meiji Research Site

    Ganzhou

  • Meiji Research Site

    Huaian

  • Meiji Research Site

    Huzhou

  • Meiji Research Site

    Nanchang

  • Meiji Research Site

    Nanning

  • Meiji Research Site

    Quanzhou

  • Meiji Research Site

    Shanghai

  • Meiji Research Site

    Shantou

  • Meiji Research Site

    Shijiazhuang

  • Meiji Research Site

    Taian

  • Meiji Research Site

    Tianjin

  • Meiji Research Site

    Xuancheng

  • Meiji Research Site

    Yunnan

  • Meiji Research Site

    Zhejiang

  • Meiji Research Site

    Zhengzhou

Other trials in China

Bulgaria4 sites
  • Meiji Research Site

    Pleven

  • Meiji Research Site

    Rousse

  • Meiji Research Site

    Silistra

  • Meiji Research Site

    Sofia

Other trials in Bulgaria

Czechia4 sites
  • Meiji Research Site

    Hradec Králové

  • Meiji Research Site

    Liberec

  • Meiji Research Site

    Prague

  • Meiji Research Site

    Ústí nad Labem

Other trials in Czechia

Estonia4 sites
  • Meiji Research Site

    Kohtla-Järve

  • Meiji Research Site

    Meegomäe, Võrumaa

  • Meiji Research Site

    Tallinn

  • Meiji Research Site

    Tartu

Other trials in Estonia

Georgia3 sites
  • Meiji Research Site

    Kutaisi

  • Meiji Research Site

    Rustavi

  • Meiji Research Site

    Tbilisi

Other trials in Georgia

Slovakia3 sites
  • Meiji Research Site

    Galanta

  • Meiji Research Site

    Rimavská Sobota

  • Meiji Research Site

    Svidník

Other trials in Slovakia

Latvia2 sites
  • Meiji Research Site

    Riga

  • Meiji Research Site

    Valmiera

Other trials in Latvia

Lithuania2 sites
  • Meiji Research Site

    Kaunas

  • Meiji Research Site

    Vilnius

Other trials in Lithuania

About this study

Official title: A Phase 3, Multi-Center, Randomized, Double-Blind Study to Evaluate the Efficacy and Safety of Cefepime/Nacubactam or Aztreonam/Nacubactam Compared to Imipenem/Cilastatin in the Treatment of Complicated Urinary Tract Infections or Acute Uncomplicated Pyelonephritis, in Adults

Phase 3 study to evaluate the efficacy and safety of cefepime/nacubactam or aztreonam/nacubactam compared to imipenem/cilastatin in the treatment of complicated urinary tract infections (cUTI) or acute uncomplicated pyelonephritis (AP).

Being tested
co-administration of cefepime and nacubactam, co-administration of aztreonam and nacubactam, imipenem/cilastatin
Keywords
OP0595, nacubactam, Integral

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

  • co-administration of aztreonam and nacubactamDrug

    2 g aztreonama and 1 g nacubactam

  • imipenem/cilastatinDrug

    1 g imipenem/1 g cilastatin

Study groups in NCT05887908
Study groupRoleWhat they receive
co-administration of cefepime and nacubactamExperimentalco-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 nacubactamExperimentalco-administration of 2 g aztreonam and 1 g nacubactam q8h (60 min. infusion)
Receives: Drug: co-administration of aztreonam and nacubactam
imipenem/cilastatinActive comparatorcombination of 1 g imipenem/1 g cilastatin q8h (60 min. infusion)
Receives: Drug: imipenem/cilastatin

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Proportion of Patients Who Achieve Composite Clinical and Microbiological Success at TOC (Test of Cure Visit) in the Microbiological Modified Intent-to-Treat (m-MITT) Population

    Composite clinical and microbiological success is defined as the composite clinical outcome of cure and the microbiological outcome of eradication.

    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 (7)
  1. Proportion of Patients Who Achieve Composite Clinical and Microbiological Outcome

    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.

    The results of subgroup analyses for only the two 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: Outcome measurements were assessed at various visits: EA (Earlly Assessment): Day4, EOT (End of Treatment): Day5 to Day14, TOC (Test of Cure visit): Day10 to Day 23, FUP (Follow-Up visit): Day17 to Day30

  2. Proportion of Patients With a Clinical Outcome of Cure

    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.

    The results of subgroup analyses for only the two 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: Outcome measurements were assessed at various visits: EA (Earlly Assessment): Day4, EOT (End of Treatment): Day5 to Day14, TOC (Test of Cure visit): Day10 to Day 23, FUP (Follow-Up visit): Day17 to Day30

  3. Proportion of Patients With a Microbiological Outcome of Eradication

    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.

    The results of subgroup analyses for only the two 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: Outcome measurements were assessed at various visits: EA (Earlly Assessment): Day4, EOT (End of Treatment): Day5 to Day14, TOC (Test of Cure visit): Day10 to Day 23, FUP (Follow-Up visit): Day17 to Day30

  4. Proportion of Patients With a Clinical Outcome of Cure at TOC in Patients With Secondary Bacteremia at Baseline

    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 signs and symptoms, with cure defined as complete resolution or significant improvement of the baseline signs and symptoms of secondary bacteremia.

    Measured: TOC (Test of Cure visit): Day 10 to Day 23 after the start of treatment

  5. Proportion of Patients With a Microbiological Outcome of Eradication at TOC in Patients With Secondary Bacteremia at Baseline

    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): Day 10 to Day 23 after the start of treatment

  6. Proportion of Patients Who Are Free From the Definition of Secondary Bacteremia AND a Clinical Outcome of Cure AND a Microbiological Outcome of Eradication From cUTI or AP at TOC in Patients With Secondary Bacteremia at Baseline

    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 cUTI/AP,Assessment is done by the same way as "Proportion of patients who achieve composite clinical 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): Day 10 to Day 23 after the start of treatment

  7. Proportion of Patients Who Are Free From Secondary Bacteremia in Patients With Secondary Bacteremia at TOC

    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 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): Day 10 to Day 23 after the start of treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted5 Jun 2023
  2. Study start23 May 2023
  3. Primary completion22 Nov 2024
  4. Study completion26 Nov 2024

Resources

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
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
614 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05887908
Sponsor's protocol ID
OP0595-5
Acronym
Integral-1
Status last verified
Nov 2025
First submitted
25 Apr 2023
Last updated
24 Dec 2025
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Takahashi S, Tateda K, Yanagihara K, Huang H, Doi Y, Yasuda M, Matsumoto K, Sumiya M, Takaya R, Suwada K, Kamiyabu S, Sasagawa Y, Minamida T, Kato S, Kondo K, Naruse T, Mikamo H. Efficacy and safety of cefepime-nacubactam and aztreonam-nacubactam compared with imipenem-cilastatin for complicated urinary tract infection or acute uncomplicated pyelonephritis (Integral-1): a double-blind, randomised phase 3 trial. Lancet. 2026 May 16;407(10542):1929-1940. doi: 10.1016/S0140-6736(26)00596-9.

    PubMed 42134354

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 imipenem/cilastatin in people with Complicated Urinary Tract Infection and Acute Pyelonephritis, run by Meiji Seika Pharma Co., Ltd. at 61 sites in 9 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 3 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 24 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 61 sites in Japan, China, Bulgaria, Czechia, Estonia and 4 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?

Yes. Results are posted in the registry (first posted 25 Nov 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Proportion of Patients Who Achieve Composite Clinical and Microbiological Success at TOC (Test of Cure Visit) in the Microbiological Modified Intent-to-Treat (m-MITT) Population (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?

On the ClinicalTrials.gov record for NCT05887908, which also lists 1 linked publication.

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 24 Dec 2025.

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