Efficacy and Safety of Cefepime/Nacubactam or Aztreonam/Nacubactam Compared to Imipenem/Cilastatin in Subjects With Complicated Urinary Tract Infections or Acute Uncomplicated Pyelonephritis (Integral-1)

Meiji Seika Pharma

Status and phase: Completed; Phase 3

Conditions: Acute Pyelonephritis; Complicated Urinary Tract Infection

Treatments: Drug: co-administration of cefepime and nacubactam; Drug: co-administration of aztreonam and nacubactam; Drug: imipenem/cilastatin

Study type: Interventional

Funder types: Industry

Identifiers

NCT05887908

OP0595-5

Details and patient eligibility

About

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).

Enrollment: 614 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. 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;
2. Weight at most 140 kg;
3. 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;

Exclusion criteria

1. 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.
2. 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.
3. Has only a known Gram-positive primary uropathogen (at least 10^5 CFU/mL), isolated from study qualifying urine culture;

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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614 participants in 3 patient groups

co-administration of cefepime and nacubactam

Experimental group

Description:

co-administration of 2 g cefepime and 1 g nacubactam q8h (60 min. infusion)

Treatment:

Drug: co-administration of cefepime and nacubactam

co-administration of aztreonam and nacubactam

Experimental group

Description:

co-administration of 2 g aztreonam and 1 g nacubactam q8h (60 min. infusion)

Treatment:

Drug: co-administration of aztreonam and nacubactam

imipenem/cilastatin

Active Comparator group

Description:

combination of 1 g imipenem/1 g cilastatin q8h (60 min. infusion)

Treatment:

Drug: imipenem/cilastatin