Safety and Efficacy of ZTI-01 (IV Fosfomycin) vs Piperacillin/Tazobactam for Treatment cUTI/AP Infections
ZEUS
Randomized, Double-Blind, Comparative Study to Evaluate the Safety and Efficacy of ZTI-01 vs Piperacillin/Tazobactam in the Treatment of cUTI/AP Infection in Hospitalized Adults
2 other identifiers
interventional
465
16 countries
68
Brief Summary
The purpose of the study is to demonstrate the safety and efficacy of ZTI-01 (IV fosfomycin) as non-inferior to piperacillin/tazobactam in overall success (clinical cure and microbiologic eradication) for the treatment of hospitalized patients with complicated urinary tract infections (cUTI) or acute pyelonephritis (AP).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Apr 2016
Shorter than P25 for phase_2
68 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
April 1, 2016
CompletedFirst Submitted
Initial submission to the registry
April 13, 2016
CompletedFirst Posted
Study publicly available on registry
April 28, 2016
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 12, 2017
CompletedStudy Completion
Last participant's last visit for all outcomes
May 30, 2017
CompletedResults Posted
Study results publicly available
December 11, 2018
CompletedMarch 7, 2019
March 1, 2019
10 months
April 13, 2016
November 16, 2018
March 5, 2019
Conditions
Outcome Measures
Primary Outcomes (1)
Number of Patients With an Overall Success
Clinical cure (resolution or significant improvement in signs and symptoms) and microbiologic eradication (baseline pathogen) in m-MITT population
TOC Visit (Day 19)
Secondary Outcomes (2)
Number of Patients With a Response of Clinical Cure in Various Protocol Populations
TOC Visit (Day 19)
Number of Patients With a Response of Microbiologic Eradication
TOC Visit (Day 19)
Study Arms (2)
ZTI-01
EXPERIMENTAL6 g ZTI-01 (IV fosfomycin) intravenously administered every 8 hours (18g total daily dose for 7-14 calendar days)
piperacillin tazobactam
ACTIVE COMPARATOR4.5 g piperacillin/tazobactam (4 g piperacillin/0.5 g tazobactam) intravenously administered every 8 hours (13.5g total daily dose for 7-14 calendar days)
Interventions
4.5g piperacillin-tazobactam intravenous infusion TID q8 hours
Eligibility Criteria
You may qualify if:
- A signed informed consent form (ICF);
- Male or female, at least 18 years of age;
- Diagnosis requires hospitalization and treatment with intravenous (IV) antibiotics;
- Documented or suspected cUTI or AP including at least 2 protocol defined signs and symptoms and a urine specimen with evidence of pyuria plus at least one protocol defined associated risk
- Pretreatment baseline urine culture specimen
- Expectation that any implanted urinary instrumentation will be removed or replaced not longer than 24 hours, after randomization;
- Expectation that patient will survive anticipated duration of the study;
- Patient requires initial hospitalization to manage the cUTI or AP;
- Women of childbearing potential have had a negative pregnancy test before randomization and be willing to consistently use a highly effective method of contraception
- Male study participants will be required to use condoms with a spermicide throughout study
You may not qualify if:
- Presence of any of the following conditions: perinephric abscess, renal corticomedullary abscess, uncomplicated urinary tract infection, recent history of trauma to the pelvis or urinary tract, polycystic kidney disease, chronic vesicoureteral reflux, previous or planned renal transplantation; patients receiving dialysis/hemodialysis/CVVH, previous or planned cystectomy or ileal loop surgery; known or suspected infection; caused by pathogen resistant to study treatment antibiotics
- Presence of suspected or confirmed acute bacterial prostatitis, orchitis, epididymitis, or chronic bacterial prostatitis as determined by history and/or physical examination;
- Gross hematuria requiring intervention;
- Urinary tract surgery within 7 days prior to randomization or urinary tract surgery planned during the study period;
- Creatinine clearance \<20 mL/min using the Cockcroft-Gault formula;
- Non-renal source of infection such as endocarditis, osteomyelitis, abscess, meningitis, or pneumonia diagnosed within 7 days prior to randomization;
- Signs of severe sepsis as defined per protocol;
- Pregnant or breastfeeding women;
- Known seizure disorder requiring current treatment with anti-seizure medication which would prohibit the patient from complying with the protocol;
- Cancer chemotherapy, immunosuppressive medications for transplantation, or medications for rejection of transplantation with 30 days of randomization;
- Significant hepatic disease or dysfunction, including known acute viral hepatitis or hepatic encephalopathy;
- ALT/AST \>5 × ULN or total bilirubin \>3 × ULN at Screening;
- Receipt of any potentially-effective systemic antibiotic with activity against Gram-negative uropathogens for more than 24 hours within the 72-hour window prior to randomization (exceptions defined in protocol);
- Requirement for additional systemic antibiotic therapy (other than study drug) or antifungal therapy for vaginal candidiasis;
- Likely to require the use of an antibiotic for cUTI or AP prophylaxis during the study;
- +10 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Nabriva Therapeutics AGlead
- Medpace, Inc.collaborator
Study Sites (68)
Unknown Facility
Pensacola, Florida, United States
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Augusta, Georgia, United States
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Columbus, Georgia, United States
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Boylston, Massachusetts, United States
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St Louis, Missouri, United States
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Butte, Montana, United States
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Brest, Belarus
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Grodno, Belarus
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Homyel, Belarus
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Minsk, Belarus
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Vitebsk, Belarus
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Plovdiv, Bulgaria
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Sofia, Bulgaria
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Slavonski Brod, Croatia
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Split, Croatia
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Zagreb, Croatia
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Brno, Czechia
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Hradec Králové, Czechia
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Liberec, Czechia
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Kohtla-Järve, Estonia
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Tallinn, Estonia
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Batumi, Georgia
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Kutaisi, Georgia
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Tbilisi, Georgia
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Ampelokipoi, Greece
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Athens, Greece
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Thessaloniki, Greece
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Budapest, Hungary
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Miskolc, Hungary
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Nagykanizsa, Hungary
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Pécs, Hungary
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Szekszárd, Hungary
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Szentes, Hungary
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Riga, Latvia
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Valmiera, Latvia
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Kaunas, Lithuania
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Klaipėda, Lithuania
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Vilnius, Lithuania
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Bielsko-Biala, Poland
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Krakow, Poland
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Lodz, Poland
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Piaseczno, Poland
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Tychy, Poland
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Wroclaw, Poland
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Zamość, Poland
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Bucharest, Romania
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Craiova, Romania
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Oradea, Romania
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Krasnoyarsk, Russia
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Moscow, Russia
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Moscow, Zelenograd, Russia
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Nizhny Novgorod, Russia
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Novosibirsk, Russia
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Penza, Russia
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Rostov-on-Don, Russia
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Saint Petersburg, Russia
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Saratov, Russia
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Smolensk, Russia
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Vsevolozhsk, Russia
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Martin, Slovakia
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Poprad, Slovakia
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Žilina, Slovakia
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Chernihiv, Ukraine
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Dnipropetrovsk, Ukraine
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Kharkiv, Ukraine
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Kyiv, Ukraine
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Odesa, Ukraine
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Zaporizhzhia, Ukraine
Related Publications (1)
Kaye KS, Rice LB, Dane AL, Stus V, Sagan O, Fedosiuk E, Das AF, Skarinsky D, Eckburg PB, Ellis-Grosse EJ. Fosfomycin for Injection (ZTI-01) Versus Piperacillin-tazobactam for the Treatment of Complicated Urinary Tract Infection Including Acute Pyelonephritis: ZEUS, A Phase 2/3 Randomized Trial. Clin Infect Dis. 2019 Nov 27;69(12):2045-2056. doi: 10.1093/cid/ciz181.
PMID: 30861061DERIVED
MeSH Terms
Interventions
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Chief Medical Officer
- Organization
- Nabriva Therapeutics plc
Study Officials
- STUDY CHAIR
Evelyn J Ellis-Grosse, PhD
Zavante Therapeutics, Inc.
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- GT60
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
April 13, 2016
First Posted
April 28, 2016
Study Start
April 1, 2016
Primary Completion
January 12, 2017
Study Completion
May 30, 2017
Last Updated
March 7, 2019
Results First Posted
December 11, 2018
Record last verified: 2019-03
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
- Time Frame
- ongoing submissions to IND
- Access Criteria
- IND/NDA submission, CTA submissions
Individual IPD data will be shared in listings with FDA, IRB/ECs, Data Monitoring Committee