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

Meiji Seika Pharma Co., Ltd.53 个研究点分布在 14 个国家目标入组 126 人2023年9月22日

适应症Complicated Urinary Tract Infection Acute Pyelonephritis Hospital-acquired Bacterial Pneumonia Ventilator-associated Bacterial Pneumonia Complicated Intra-abdominal Infection

干预措施co-administration of cefepime and nacubactam co-administration of aztreonam and nacubactam BAT

概览

阶段: 3 期
干预措施: co-administration of cefepime and nacubactam
疾病 / 适应症: Complicated Urinary Tract Infection
发起方: Meiji Seika Pharma Co., Ltd.
入组人数: 126
试验地点: 53
主要终点: 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.
状态: 已完成
最后更新: 19天前

概览研究者入排标准研究组 & 干预措施结局指标研究点相似试验

概览

简要总结

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.

注册库

clinicaltrials.gov

开始日期

2023年9月22日

结束日期

2025年9月1日

最后更新

19天前

研究类型

Interventional

研究设计

Parallel

性别

All

研究者

发起方

Meiji Seika Pharma Co., Ltd.

责任方

Sponsor

入排标准

入选标准

•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:
•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.

排除标准

•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;

研究组 & 干预措施

co-administration of cefepime and nacubactam

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

干预措施: co-administration of cefepime and nacubactam

co-administration of aztreonam and nacubactam

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

干预措施: co-administration of aztreonam and nacubactam

BAT

Best Available Therapy

干预措施: BAT

结局指标

主要结局

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.

时间窗: 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.

次要结局

The proportion of patients with a clinical outcome of cure per type of resistance(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(TOC (Test of Cure visit):7 [±2] days after EOT [Day 10 to 23])
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(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(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(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(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(EOT (End of Treatment): [Day 5 to Day 16])
Change in the partial pressure of oxygen to FiO2 ratio from baseline to EOT for HABP/VABP patients(EOT (End of Treatment): [Day 5 to Day 16])
Time (days) to extubation in patients who are on the ventilator at baseline for HABP/VABP patients(Up to EOT (End of Treatment): [Day 5 to Day 16])
The proportion of patients with clinical outcome of recurrence at the FUP for HABP/VABP patients(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(FUP(Follow-Up visit):14 [±2] days after EOT [Day 17 to Day 30])
The proportion of patients with overall treatment success across all infection types at TOC for secondary bacteremia patients(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(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(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(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(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(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(TOC (Test of Cure visit):7 [±2] days after EOT [Day 10 to 23])
The proportion of patients with overall treatment outcome of success across all infection types(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)
Total ventilator days measured from time of randomization to EOT for HABP/VABP patients(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(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(Up to EOT (End of Treatment): [Day 5 to Day 14])
The proportion of patients with overall treatment outcome of success across all infection types(Outcome measurements were assessed at various visits: EA (Earlly 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(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(7 [±2] days after EOT [Day 10 to 23])
The all-cause mortality rate at Day 28 for secondary bacteremia patients(Day 28 (+ 2days))
The all-cause mortality rate at Day 28 by each infection type (ie, cUTI/AP, HABP/VABP, or cIAI) and across all infection types(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(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(7 [±2] days after EOT [Day 10 to 23])
The proportion of patients with composite clinical and microbiological success for cUTI/AP patients(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(14 [±2] days after EOT [Day 17 to Day 30])
Total ventilator days measured from time of randomization to EOT for HABP/VABP patients(EOT [Day 5 to Day 16])
Change in the partial pressure of oxygen to FiO2 ratio from baseline to EOT for HABP/VABP patients(EOT [Day 5 to Day 16])
Time (days) to extubation in patients who are on the ventilator at baseline for HABP/VABP patients(Up to EOT [Day 5 to Day 16])
The proportion of patients with clinical outcome of recurrence at the FUP for HABP/VABP patients(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(14 [±2] days after EOT [Day 17 to Day 30])
The proportion of patients with overall treatment success across all infection types at TOC for secondary bacteremia patients(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(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(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(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(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(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(7 [±2] days after EOT [Day 10 to 23])