This study will assess the safety and efficacy of cefepime/VNRX-5133 compared with meropenem in both eradication of bacteria and in symptomatic response in patients with cUTIs.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
661
Cefepime/VNRX-5133 administered q8h intravenously (IV) over a 2-hour period for 7 days (up to 14 days for patients with bacteremia). Patients will also receive meropenem placebo administered via IV over 30 minutes.
Meropenem will be administered q8h IV over 30 minutes for 7 days (up to 14 days for patients with bacteremia). Patients will also receive cefepime/VNRX-5133 placebo administered via IV over a 2-hour period.
Composite Success at Test of Cure (TOC) in the Microbiological Intent-to-treat (microITT) Population
Microbiologic success is eradication defined as demonstration that any gram-negative bacterial pathogen found at study entry (≥10\^5 CFU/mL) is eradicated to \<10\^3 CFU/mL. Clinical success is defined as symptomatic resolution or return to pre-morbid baseline of all UTI-core symptoms and patient is alive, and patient has not received additional antibacterial therapy for cUTI.
Time frame: Assessed at Test of Cure visit (occurred once per participant between Study Days 19 to 23)
Microbiologic Success at Test of Cure (TOC) in the microITT Population
Microbiologic success is eradication defined as demonstration that any gram-negative bacterial pathogen found at study entry (≥10\^5 CFU/mL) is eradicated to \<10\^3 CFU/mL.
Time frame: Assessed at Test of Cure visit (occurred once per participant between Study Days 19 to 23)
Clinical Success at Test of Cure (TOC) in the microITT Population
Symptomatic resolution or return to pre-morbid baseline of all UTI-core symptoms and patient is alive, and patient has not received additional antibacterial therapy for cUTI.
Time frame: Assessed at Test of Cure visit (occurred once per participant between Study Days 19 to 23)
Composite Success at Test of Cure (TOC) in the Extended Microbiological Intent-to-treat (emicroITT) Population
Microbiologic success is eradication defined as demonstration that any gram-negative bacterial pathogen found at study entry (≥10\^5 CFU/mL) is eradicated to \<10\^3 CFU/mL. Symptomatic clinical success is defined as symptomatic resolution or return to pre-morbid baseline of all UTI-core symptoms and patient is alive, and patient has not received additional antibacterial therapy for cUTI.
Time frame: Assessed at Test of Cure visit (occurred once per participant between Study Days 19 to 23)
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Site 184003
Buena Park, California, United States
Site 184002
Chula Vista, California, United States
Site 184001
La Mesa, California, United States
184012
Northridge, California, United States
Site 103203
Córdoba, Argentina
Site 107601
Belo Horizonte, Brazil
Site 107608
São Paulo, Brazil
Site 110009
Gabrovo, Bulgaria
Site 110002
Pleven, Bulgaria
Site 110007
Plovdiv, Bulgaria
...and 68 more locations
Composite Success at End of Treatment (EOT) in the microITT Population
Microbiologic success is eradication defined as demonstration that any gram-negative bacterial pathogen found at study entry (≥10\^5 CFU/mL) is eradicated to \<10\^3 CFU/mL. Clinical success is defined as symptomatic resolution or return to pre-morbid baseline of all UTI-core symptoms and patient is alive, and patient has not received additional antibacterial therapy for cUTI.
Time frame: Assessed within 24 hours after last IV dose (up to 15 days from start of treatment)
Microbiological Success at End of Treatment (EOT) in the microITT Population
Microbiologic success is eradication defined as demonstration that any gram-negative bacterial pathogen found at study entry (≥10\^5 CFU/mL) is eradicated to \<10\^3 CFU/mL.
Time frame: Assessed within 24 hours after last IV dose (up to 15 days from start of treatment)
Clinical Success at End of Treatment (EOT) in the microITT Population
Clinical success is defined as symptomatic resolution or return to pre-morbid baseline of all UTI-core symptoms and patient is alive, and patient has not received additional antibacterial therapy for cUTI.
Time frame: Assessed within 24 hours after last IV dose (up to 15 days from start of treatment)
Composite Success at Late Follow Up (LFU) in the microITT Population
Microbiologic success is eradication defined as demonstration that any gram-negative bacterial pathogen found at study entry (≥10\^5 CFU/mL) is eradicated to \<10\^3 CFU/mL. Clinical success is defined as symptomatic resolution or return to pre-morbid baseline of all UTI-core symptoms and patient is alive, and patient has not received additional antibacterial therapy for cUTI.
Time frame: Assessed at Late Follow Up visit (occurred once per participant between Study Days 28 to 35)
Microbiological Success at Late Follow Up (LFU) in the microITT Population
Microbiologic success is eradication defined as demonstration that any gram-negative bacterial pathogen found at study entry (≥10\^5 CFU/mL) is eradicated to \<10\^3 CFU/mL.
Time frame: Assessed at Late Follow Up visit (occurred once per participant between Study Days 28 to 35)
Clinical Success at Late Follow Up (LFU) in the microITT Population
Clinical success is defined as symptomatic resolution or return to pre-morbid baseline of all UTI-core symptoms and patient is alive, and patient has not received additional antibacterial therapy for cUTI.
Time frame: Assessed at Late Follow Up visit (occurred once per participant between Study Days 28 to 35)
Investigator Opinion of Clinical Success at Test of Cure (TOC) in the microITT Population
The proportion of patients with clinical success based on investigator opinion at TOC.
Time frame: Assessed at Test of Cure visit (occurred once per participant between Study Days 19 to 23)
Composite Success in Patients With Cefepime-Resistant Pathogens at End of Treatment (EOT) in the microITT Population
Microbiologic success is eradication defined as demonstration that any gram-negative bacterial pathogen found at study entry (≥10\^5 CFU/mL) is eradicated to \<10\^3 CFU/mL. Clinical success is defined as symptomatic resolution or return to pre-morbid baseline of all UTI-core symptoms and patient is alive, and patient has not received additional antibacterial therapy for cUTI.
Time frame: Assessed within 24 hours after last IV dose (up to 15 days from start of treatment)
Microbiologic Success in Patients With Cefepime-Resistant Pathogens at End of Treatment (EOT) in the microITT Population
Microbiologic success is eradication defined as demonstration that any gram-negative bacterial pathogen found at study entry (≥10\^5 CFU/mL) is eradicated to \<10\^3 CFU/mL.
Time frame: Assessed within 24 hours after last IV dose (up to 15 days from start of treatment)
Clinical Success in Patients With Cefepime-Resistant Pathogens at End of Treatment (EOT) in the microITT Population
Clinical success is defined as symptomatic resolution or return to pre-morbid baseline of all UTI-core symptoms and patient is alive, and patient has not received additional antibacterial therapy for cUTI.
Time frame: Assessed within 24 hours after last IV dose (up to 15 days from start of treatment)
Composite Success in Patients With Cefepime-Resistant Pathogens at Test of Cure (TOC) in the microITT Population
Microbiologic success is eradication defined as demonstration that any gram-negative bacterial pathogen found at study entry (≥10\^5 CFU/mL) is eradicated to \<10\^3 CFU/mL. Clinical success is defined as symptomatic resolution or return to pre-morbid baseline of all UTI-core symptoms and patient is alive, and patient has not received additional antibacterial therapy for cUTI.
Time frame: Assessed at Test of Cure visit (occurred once per participant between Study Days 19 to 23)
Microbiologic Success in Patients With Cefepime-Resistant Pathogens at Test of Cure (TOC) in the microITT Population
Microbiologic success is eradication defined as demonstration that any gram-negative bacterial pathogen found at study entry (≥10\^5 CFU/mL) is eradicated to \<10\^3 CFU/mL.
Time frame: Assessed at Test of Cure visit (occurred once per participant between Study Days 19 to 23)
Clinical Success in Patients With Cefepime-Resistant Pathogens at Test of Cure (TOC) in the microITT Population
Clinical success is defined as symptomatic resolution or return to pre-morbid baseline of all UTI-core symptoms and patient is alive, and patient has not received additional antibacterial therapy for cUTI.
Time frame: Assessed at Test of Cure visit (occurred once per participant between Study Days 19 to 23)
Composite Success in Patients With Cefepime-Resistant Pathogens at Late Follow Up (LFU) in the microITT Population
Microbiologic success is eradication defined as demonstration that any gram-negative bacterial pathogen found at study entry (≥10\^5 CFU/mL) is eradicated to \<10\^3 CFU/mL. Clinical success is defined as symptomatic resolution or return to pre-morbid baseline of all UTI-core symptoms and patient is alive, and patient has not received additional antibacterial therapy for cUTI.
Time frame: Assessed at Late Follow Up visit (occurred once per participant between Study Days 28 to 35)
Microbiologic Success in Patients With Cefepime-Resistant Pathogens at Late Follow Up (LFU) in the microITT Population
Microbiologic success is eradication defined as demonstration that any gram-negative bacterial pathogen found at study entry (≥10\^5 CFU/mL) is eradicated to \<10\^3 CFU/mL.
Time frame: Assessed at Late Follow Up visit (occurred once per participant between Study Days 28 to 35)
Clinical Success in Patients With Cefepime-Resistant Pathogens at Late Follow Up (LFU) in the microITT Population
Clinical success is defined as symptomatic resolution or return to pre-morbid baseline of all UTI-core symptoms and patient is alive, and patient has not received additional antibacterial therapy for cUTI.
Time frame: Assessed at Late Follow Up visit (occurred once per participant between Study Days 28 to 35)
Composite Success at End of Treatment (EOT) in the Microbiologically-Evaluable (ME) Population
Microbiologic success is eradication defined as demonstration that any gram-negative bacterial pathogen found at study entry (≥10\^5 CFU/mL) is eradicated to \<10\^3 CFU/mL. Clinical success is defined as symptomatic resolution or return to pre-morbid baseline of all UTI-core symptoms and patient is alive, and patient has not received additional antibacterial therapy for cUTI.
Time frame: Assessed within 24 hours after last IV dose (up to 15 days from start of treatment)
Microbiologic Success at End of Treatment (EOT) in the ME Population
Microbiologic success is eradication defined as demonstration that any gram-negative bacterial pathogen found at study entry (≥10\^5 CFU/mL) is eradicated to \<10\^3 CFU/mL.
Time frame: Assessed within 24 hours after last IV dose (up to 15 days from start of treatment)
Composite Success at Test of Cure (TOC) in the ME Population
Microbiologic success is eradication defined as demonstration that any gram-negative bacterial pathogen found at study entry (≥10\^5 CFU/mL) is eradicated to \<10\^3 CFU/mL. Symptomatic clinical success is defined as symptomatic resolution or return to pre-morbid baseline of all UTI-core symptoms and patient is alive, and patient has not received additional antibacterial therapy for cUTI.
Time frame: Assessed at Test of Cure visit (occurred once per participant between Study Days 19 to 23)
Microbiologic Success at Test of Cure (TOC) in the ME Population
Microbiologic success is eradication defined as demonstration that any gram-negative bacterial pathogen found at study entry (≥10\^5 CFU/mL) is eradicated to \<10\^3 CFU/mL.
Time frame: Assessed at Test of Cure visit (occurred once per participant between Study Days 19 to 23)
Composite Success at Late Follow Up (LFU) in the ME Population
Microbiologic success is eradication defined as demonstration that any gram-negative bacterial pathogen found at study entry (≥10\^5 CFU/mL) is eradicated to \<10\^3 CFU/mL. Symptomatic clinical success is defined as symptomatic resolution or return to pre-morbid baseline of all UTI-core symptoms and patient is alive, and patient has not received additional antibacterial therapy for cUTI.
Time frame: Assessed at Late Follow Up visit (occurred once per participant between Study Days 28 to 35)
Microbiologic Success at Late Follow Up (LFU) in the ME Population
Microbiologic success is eradication defined as demonstration that any gram-negative bacterial pathogen found at study entry (≥10\^5 CFU/mL) is eradicated to \<10\^3 CFU/mL.
Time frame: Assessed at Late Follow Up visit (occurred once per participant between Study Days 28 to 35)
Composite Success in Patients With Cefepime-Resistant Pathogens at the End of Treatment (EOT) in the ME Population
Microbiologic success is eradication defined as demonstration that any gram-negative bacterial pathogen found at study entry (≥10\^5 CFU/mL) is eradicated to \<10\^3 CFU/mL. Symptomatic clinical success is defined as symptomatic resolution or return to pre-morbid baseline of all UTI-core symptoms and patient is alive, and patient has not received additional antibacterial therapy for cUTI.
Time frame: Assessed within 24 hours after last IV dose (up to 15 days from start of treatment)
Microbiologic Success in Patients With Cefepime-Resistant Pathogens at the End of Treatment (EOT) in the ME Population
Microbiologic success is eradication defined as demonstration that any gram-negative bacterial pathogen found at study entry (≥10\^5 CFU/mL) is eradicated to \<10\^3 CFU/mL.
Time frame: Assessed within 24 hours after last IV dose (up to 15 days from start of treatment)
Composite Success in Patients With Cefepime-Resistant Pathogens at Test of Cure (TOC) in the ME Population
Microbiologic success is eradication defined as demonstration that any gram-negative bacterial pathogen found at study entry (≥10\^5 CFU/mL) is eradicated to \<10\^3 CFU/mL. Symptomatic clinical success is defined as symptomatic resolution or return to pre-morbid baseline of all UTI-core symptoms and patient is alive, and patient has not received additional antibacterial therapy for cUTI.
Time frame: Assessed at Test of Cure visit (occurred once per participant between Study Days 19 to 23)
Microbiologic Success in Patients With Cefepime-Resistant Pathogens at Test of Cure (TOC) in the ME Population
Microbiologic success is eradication defined as demonstration that any gram-negative bacterial pathogen found at study entry (≥10\^5 CFU/mL) is eradicated to \<10\^3 CFU/mL.
Time frame: Assessed at Test of Cure visit (occurred once per participant between Study Days 19 to 23)
Composite Success in Cefepime-Resistant Pathogens at Late Follow Up (LFU) in the ME Population
Microbiologic success is eradication defined as demonstration that any gram-negative bacterial pathogen found at study entry (≥10\^5 CFU/mL) is eradicated to \<10\^3 CFU/mL. Symptomatic clinical success is defined as symptomatic resolution or return to pre-morbid baseline of all UTI-core symptoms and patient is alive, and patient has not received additional antibacterial therapy for cUTI.
Time frame: Assessed at Late Follow Up visit (occurred once per participant between Study Days 28 to 35)
Microbiologic Success in Cefepime-Resistant Pathogens at Late Follow Up (LFU) in the ME Population
Microbiologic success is eradication defined as demonstration that any gram-negative bacterial pathogen found at study entry (≥10\^5 CFU/mL) is eradicated to \<10\^3 CFU/mL.
Time frame: Assessed at Late Follow Up visit (occurred once per participant between Study Days 28 to 35)
Clinical Success at End of Treatment (EOT) in the Clinically Evaluable (CE) Population
Symptomatic clinical success is defined as symptomatic resolution or return to pre-morbid baseline of all UTI-core symptoms and patient is alive, and patient has not received additional antibacterial therapy for cUTI.
Time frame: Assessed within 24 hours after last IV dose (up to 15 days from start of treatment)
Clinical Success at Test of Cure (TOC) in the CE Population
Symptomatic clinical success is defined as symptomatic resolution or return to pre-morbid baseline of all UTI-core symptoms and patient is alive, and patient has not received additional antibacterial therapy for cUTI.
Time frame: Assessed at Test of Cure visit (occurred once per participant between Study Days 19 to 23)
Clinical Success at Late Follow Up (LFU) in the CE Population
Symptomatic clinical success is defined as symptomatic resolution or return to pre-morbid baseline of all UTI-core symptoms and patient is alive, and patient has not received additional antibacterial therapy for cUTI.
Time frame: Assessed at Late Follow Up visit (occurred once per participant between Study Days 28 to 35)
Clinical Success in Patients With Cefepime-Resistant Pathogens at End of Treatment (EOT) in the CE Population
Symptomatic clinical success is defined as symptomatic resolution or return to pre-morbid baseline of all UTI-core symptoms and patient is alive, and patient has not received additional antibacterial therapy for cUTI.
Time frame: Assessed within 24 hours after last IV dose (up to 15 days from start of treatment)
Clinical Success in Patients With Cefepime-Resistant Pathogens at Test of Cure (TOC) in the CE Population
Symptomatic clinical success is defined as symptomatic resolution or return to pre-morbid baseline of all UTI-core symptoms and patient is alive, and patient has not received additional antibacterial therapy for cUTI.
Time frame: Assessed at Test of Cure visit (occurred once per participant between Study Days 19 to 23)
Clinical Success in Patients With Cefepime-Resistant Pathogens at Late Follow Up (LFU) in the CE Population
Symptomatic clinical success is defined as symptomatic resolution or return to pre-morbid baseline of all UTI-core symptoms and patient is alive, and patient has not received additional antibacterial therapy for cUTI.
Time frame: Assessed at Late Follow Up visit (occurred once per participant between Study Days 28 to 35)
Per-Pathogen Microbiologic Eradication at End of Treatment (EOT) in the microITT Population
Per-pathogen eradication by baseline gram-negative pathogens. The number analyzed corresponds to the number of specified pathogens. The number is the percent of the specified pathogen identified at baseline in each treatment group that had been eradicated.
Time frame: Assessed within 24 hours after last IV dose (up to 15 days from start of treatment)
Per-Pathogen Microbiologic Eradication at Test of Cure (TOC) in the microITT Population
Per-pathogen eradication by baseline gram-negative pathogens. The number analyzed corresponds to the number of specified pathogens. The number is the percent of the specified pathogen identified at baseline in each treatment group that had been eradicated.
Time frame: Assessed at Test of Cure visit (occurred once per participant between Study Days 19 to 23)
Per-Pathogen Microbiologic Eradication at Late Follow Up (LFU) in the microITT Population
Per-pathogen eradication by baseline gram-negative pathogens. The number analyzed corresponds to the number of specified pathogens. The number is the percent of the specified pathogen identified at baseline in each treatment group that had been eradicated.
Time frame: Assessed at Late Follow Up visit (occurred once per participant between Study Days 28 to 35)
Per-Pathogen Microbiologic Eradication in Patients With Cefepime-Resistant Pathogens at End of Treatment (EOT) in the microITT Population
Per-pathogen eradication by baseline gram-negative pathogens (only pathogens identified 10 or more times are reported). The number analyzed corresponds to the number of specified pathogens. The number is the percent of the specified pathogen identified at baseline in each treatment group that had been eradicated.
Time frame: Assessed within 24 hours after last IV dose (up to 15 days from start of treatment)
Per-Pathogen Microbiologic Eradication in Patients With Cefepime-Resistant Pathogens at Test of Cure (TOC) in the microITT Population
Per-pathogen eradication by baseline gram-negative pathogens (only pathogens identified 10 or more times are reported). The number analyzed corresponds to the number of specified pathogens. The number is the percent of the specified pathogen identified at baseline in each treatment group that had been eradicated.
Time frame: Assessed at Test of Cure visit (occurred once per participant between Study Days 19 to 23)
Per-Pathogen Microbiologic Eradication in Patients With Cefepime-Resistant Pathogens at Late Follow Up (LFU) in the microITT Population
Per-pathogen eradication by baseline gram-negative pathogens (only pathogens identified 10 or more times are reported). The number analyzed corresponds to the number of specified pathogens. The number is the percent of the specified pathogen identified at baseline in each treatment group that had been eradicated.
Time frame: Assessed at Late Follow Up visit (occurred once per participant between Study Days 28 to 35)
Per-Pathogen Microbiologic Eradication at End of Treatment (EOT) in the ME Population
Per-pathogen eradication by baseline gram-negative pathogens. The number analyzed corresponds to the number of specified pathogens. The number is the percent of the specified pathogen identified at baseline in each treatment group that had been eradicated.
Time frame: Assessed within 24 hours after last IV dose (up to 15 days from start of treatment)
Per-Pathogen Microbiologic Eradication at Test of Cure (TOC) in the ME Population
Per-pathogen eradication by baseline gram-negative pathogens. The number analyzed corresponds to the number of specified pathogens. The number is the percent of the specified pathogen identified at baseline in each treatment group that had been eradicated.
Time frame: Assessed at Test of Cure visit (occurred once per participant between Study Days 19 to 23)
Per-Pathogen Microbiologic Eradication at Late Follow Up (LFU) in the ME Population
Per-pathogen eradication by baseline gram-negative pathogens. The number analyzed corresponds to the number of specified pathogens. The number is the percent of the specified pathogen identified at baseline in each treatment group that had been eradicated.
Time frame: Assessed at Late Follow Up visit (occurred once per participant between Study Days 28 to 35)
Per-Pathogen Microbiologic Eradication in Patients With Cefepime-Resistant Pathogens at End of Treatment (EOT) in the ME Population
Per-pathogen eradication by baseline gram-negative pathogens (only pathogens identified 10 or more times are reported). The number analyzed corresponds to the number of specified pathogens. The number is the percent of the specified pathogen identified at baseline in each treatment group that had been eradicated.
Time frame: Assessed within 24 hours after last IV dose (up to 15 days from start of treatment)
Per-Pathogen Microbiologic Eradication in Patients With Cefepime-Resistant Pathogens at Test of Cure TOC in the ME Population
Per-pathogen eradication by baseline gram-negative pathogens (only pathogens identified 10 or more times are reported). The number analyzed corresponds to the number of specified pathogens. The number is the percent of the specified pathogen identified at baseline in each treatment group that had been eradicated.
Time frame: Assessed at Test of Cure visit (occurred once per participant between Study Days 19 to 23)
Per-Pathogen Microbiologic Eradication in Patients With Cefepime-Resistant Pathogens at Late Follow Up (LFU) in the ME Population
Per-pathogen eradication by baseline gram-negative pathogens (only pathogens identified 10 or more times are reported). The number analyzed corresponds to the number of specified pathogens. The number is the percent of the specified pathogen identified at baseline in each treatment group that had been eradicated.
Time frame: Assessed at Late Follow Up visit (occurred once per participant between Study Days 28 to 35)