Clinical trial • Phase II • Infectious Disease
Aztreonam, Avibactam sodium for Sepsis | Gram-negative bacterial infections | Complicated urinary tract infection | Bloodstream infection | Hospital-acquired pneumonia | Ventilator-associated pneumonia | Complicated intra-abdominal infection
Phase II trial of Aztreonam, Avibactam sodium for Sepsis | Gram-negative bacterial infections | Complicated urinary tract infection | Bloodstream infectio…
Overview
- Trial Therapeutic Area
- Infectious Disease
- Trial Disease
- Sepsis | Gram-negative bacterial infections | Complicated urinary tract infection | Bloodstream infection | Hospital-acquired pneumonia | Ventilator-associated pneumonia | Complicated intra-abdominal infection
- Trial Stage
- Phase II
- Drug Modality
- Small molecule
- Paediatric Trial
- Yes
Key dates
- Initial CTIS Submission Date
- 20-12-2024
- First CTIS Authorization Date
- 30-04-2025
Trial design
open-label, atm-avi: iv atm-avi loading dose according to weight and age; part b maintenance doses described as q6h or q8h according to age for a minimum of 3 days and maximum of 14 days. atm-avi + mtz: participants in part b with ciai will receive iv atm-avi plus metronidazole; for other infections mtz will be given at investigator discretion if anaerobes are suspected or confirmed.-controlled Phase II trial across 27 sites in Italy, Hungary, Greece and others.
- Open Label
- Yes
- Comparator
- ATM-AVI: IV ATM-AVI loading dose according to weight and age; Part B maintenance doses described as q6h or q8h according to age for a minimum of 3 days and maximum of 14 days. ATM-AVI + MTZ: Participants in Part B with cIAI will receive IV ATM-AVI plus metronidazole; for other infections MTZ will be given at investigator discretion if anaerobes are suspected or confirmed.
- Single Multiple Or Escalation Dose Combined
- Yes
- Target Sample Size
- 26
- Trial Duration For Participant
- 49
Eligibility
Recruits 26 paediatric patients.
- Vulnerable Population
- Participants are neonates and infants from birth to <9 months (vulnerable population). Informed consent materials and pediatric informed consent/ICD documents are provided (parent/legal representative consent is required); assent is not applicable for the enrolled age group.
Inclusion criteria
- {"criterion_text":"- Hospitalized with age from birth <9 months, including preterm birth"}
- {"criterion_text":"- Part A: Receiving IV antibiotics for treatment of suspected or confirmed bacterial infection, including but not limited to cIAI, cUTI, HAP/VAP, BSI, or sepsis."}
- {"criterion_text":"- Part B: Suspected or confirmed gram-negative bacterial infection requiring IV antibiotics, including but not limited to cIAI, cUTI, HAP/VAP, BSI, or sepsis."}
Exclusion criteria
- {"criterion_text":"- Received any other investigational medicinal product within the longer of 30 days or 5 half-lives before enrollment."}
- {"criterion_text":"- Any medical or laboratory abnormality that may increase the risk of study participation or, in the investigator’s judgment, make the participant inappropriate for the study."}
- {"criterion_text":"- Severe renal impairment or known significant renal disease, as evidenced by elevated serum creatinine at screening, or urinary output <0.5 mL/kg/h for 6 consecutive hours or requirement for dialysis."}
- {"criterion_text":"- Part B Only: Received >24 hours of systemic antibiotic treatment for gram-negative organisms at time of enrollment, unless documented treatment failure or lack of improvement in at least one objective sign or symptom of infection after ≥48 hours of antibiotics."}
Endpoints
Primary endpoints
- {"endpoint_text":"- PK parameters including clearance (CL), maximum plasma concentration (Cmax), area under the plasma concentration time curve (AUC) and half-life (t1/2)","definition_or_measurement_approach":"Pharmacokinetic parameters measured from plasma samples (clearance, Cmax, AUC, t1/2)."}
- {"endpoint_text":"- Plasma concentrations of ATM and AVI on Day 1 and at steady state (Day 2 or later)","definition_or_measurement_approach":"Measurement of plasma concentrations of aztreonam (ATM) and avibactam (AVI) on Day 1 and at steady state (Day 2 or later)."}
- {"endpoint_text":"- Adverse events (AEs) and Serious Adverse Events (SAEs)","definition_or_measurement_approach":"Recording and reporting of AEs and SAEs per standard safety assessment procedures."}
- {"endpoint_text":"- Adverse events leading to discontinuation and adverse events resulting in death","definition_or_measurement_approach":"Capture of AEs leading to study treatment discontinuation and AEs resulting in death."}
- {"endpoint_text":"- Assessments of liver and renal functions tests at baseline, while on treatment and after end of treatment","definition_or_measurement_approach":"Laboratory assessments of liver and renal function at baseline, during treatment and after end of treatment."}
Secondary endpoints
- {"endpoint_text":"- Clinical outcomes at End of Intravenous Treatment (EOIV), End of Treatment (EOT), and Test of Cure (TOC). (Pat B only)","definition_or_measurement_approach":"Assessment of clinical outcomes at EOIV, EOT and TOC timepoints (Part B participants)."}
- {"endpoint_text":"- Per-pathogen microbiological response at EOIV/EOT, and TOC.","definition_or_measurement_approach":"Microbiological response assessed per pathogen at EOIV/EOT and TOC."}
- {"endpoint_text":"- Per-participant microbiological response at TOC","definition_or_measurement_approach":"Microbiological response assessed per participant at TOC."}
- {"endpoint_text":"- Emergent infection","definition_or_measurement_approach":"Recording of emergent infections during study treatment and follow-up."}
Recruitment
- Planned Sample Size
- 26
- Recruitment Window Months
- 37
- Consent Approach
- Informed consent is obtained from parent(s)/legal representative(s) using pediatric subject information and consent/ICD documents (Part A and Part B specific ICF/ICD documents and a pediatric privacy supplement). Country/language-specific ICF/ICD and recruitment materials are available (documents in English, Italian, Hungarian, Greek, Bulgarian, Slovak, Spanish are present in the dossier). Assent is not applicable for neonates/infants enrolled.
Methods
- HCP study posters (country-specific versions) — materials for healthcare professionals to inform about the study (documents present for Italy, Hungary, Greece, Bulgaria, Slovakia, Spain).
- Study brochures — participant/parent-facing information brochures available in country-specific versions.
- Informed consent flipbook — consent/assent informational flipbook materials (country-specific versions) to support consent discussions.
- Pediatric education material — materials aimed at parents/guardians and healthcare staff to explain pediatric aspects of participation.
- Recruitment and informed consent procedure documents — formal recruitment and consent procedures provided (country-specific documents).
Geography
- Total Number Of Sites
- 27
- Total Number Of Participants
- 26
Italy
- Earliest CTIS Part Ii Submission Date
- 21-01-2025
- Latest Decision Or Authorization Date
- 30-04-2025
- Processing Time Days
- 99
- Number Of Sites
- 5
- Number Of Participants
- 5
Sites
- Site Name
- Azienda Ospedale-Universita Padova
- Department Name
- Dipartimento di Salute della donna e del bambino
- Contact Person Name
- Eugenio Baraldi
- Contact Person Email
- eugenio.baraldi@unipd.it
- Site Name
- Azienda Socio Sanitaria Territoriale Degli Spedali Civili Di Brescia
- Department Name
- Pediatria
- Contact Person Name
- Raffaele Badolato
- Contact Person Email
- raffaele.badolato@unibs.it
- Site Name
- Azienda Sanitaria Locale Della Provincia Di Biella
- Department Name
- SCDU Pediatria e Neonatologia
- Contact Person Name
- Paolo Manzoni
- Contact Person Email
- paolo.manzoni@aslbi.piemonte.it
- Site Name
- Azienda Ospedaliera Universitaria Meyer IRCCS
- Department Name
- SOD Malattie Infettive Pediatriche
- Contact Person Name
- Carlotta Montagnani
- Contact Person Email
- carlotta.montagnani@meyer.it
- Site Name
- ASST Fatebenefratelli Sacco
- Department Name
- Pediatria
- Contact Person Name
- Vania Giacomet
- Contact Person Email
- vania.giacomet@unimi.it
Hungary
- Earliest CTIS Part Ii Submission Date
- 14-03-2025
- Latest Decision Or Authorization Date
- 06-05-2025
- Processing Time Days
- 53
- Number Of Sites
- 5
- Number Of Participants
- 4
Sites
- Site Name
- Semmelweis University
- Department Name
- Gyermekgyógyászati Klinika
- Contact Person Name
- Attila Szabó
- Contact Person Email
- szabo.attila@med.semmelweis-univ.hu
- Site Name
- Semmelweis University
- Department Name
- Gyermekgyógyászati Klinika
- Contact Person Name
- Krisztina Kalocsai
- Contact Person Email
- kalocsai.k@gmail.com
- Site Name
- Eszak-Budai Szent Janos Centrumkorhaz
- Department Name
- Gyermek-, Koraszülött és Csecsemőosztály
- Contact Person Name
- Vera Tory
- Contact Person Email
- toryveron@gmail.com
- Site Name
- University Of Debrecen
- Department Name
- Gyermekgyógyászati Klinika, Neonatológia
- Contact Person Name
- Gergely Balázs
- Contact Person Email
- balazs.gergely@med.unideb.hu
- Site Name
- Kanizsai Dorottya Korhaz
- Department Name
- Csecsemő és Gyermekgyógyászati Osztály
- Contact Person Name
- Réka Olosz
- Contact Person Email
- oloszr@hotmail.com
Greece
- Earliest CTIS Part Ii Submission Date
- 21-01-2025
- Latest Decision Or Authorization Date
- 30-04-2025
- Processing Time Days
- 99
- Number Of Sites
- 4
- Number Of Participants
- 4
Sites
- Site Name
- University General Hospital Of Heraklion
- Department Name
- Pediatric Intensive Care
- Contact Person Name
- Ilia Stavroula
- Contact Person Email
- stavroula.ilia@uoc.gr
- Site Name
- Ippokratio General Hospital Of Thessaloniki
- Department Name
- 3rd Pediatric Department
- Contact Person Name
- Elias Iosifidis
- Contact Person Email
- iosifidish@gmail.com
- Site Name
- General University Hospital Of Larissa
- Department Name
- Department of Pediatrics
- Contact Person Name
- Ioanna Grivea
- Contact Person Email
- ioanna.grivea@gmail.com
- Site Name
- University General Hospital Attikon
- Department Name
- 3rd Department of Pediatrics
- Contact Person Name
- Vassiliki Papaevangelou
- Contact Person Email
- vpapaev@med.uoa.gr
Bulgaria
- Earliest CTIS Part Ii Submission Date
- 21-01-2025
- Latest Decision Or Authorization Date
- 02-05-2025
- Processing Time Days
- 101
- Number Of Sites
- 4
- Number Of Participants
- 4
Sites
- Site Name
- Universitetska Mnogoprofilna bolnica za aktivno lechenie Deva Maria EOOD
- Department Name
- Department of Neonatology
- Contact Person Name
- Krasimira Dobreva
- Contact Person Email
- k.dobreva@mail.bg
- Site Name
- University Multiprofile Hospital For Active Treatment Saint Georgi EAD
- Department Name
- Clinic of Pediatric Surgery
- Contact Person Name
- Penka Stefanova-Peeva
- Contact Person Email
- pepi_stef@hotmail.com
- Site Name
- University Multiprofessional Hospital For Active Treatment Kanev AD
- Department Name
- Department of Neonatology
- Contact Person Name
- Liliya Georgieva
- Contact Person Email
- lilidg@mail.bg
- Site Name
- Acibadem City Clinic Tokuda University Hospital EAD
- Department Name
- Department of Neonatology
- Contact Person Name
- Radka Maslarska
- Contact Person Email
- r_maslarska17@abv.bg
Slovakia
- Earliest CTIS Part Ii Submission Date
- 01-04-2025
- Latest Decision Or Authorization Date
- 30-04-2025
- Processing Time Days
- 29
- Number Of Sites
- 5
- Number Of Participants
- 5
Sites
- Site Name
- Univerzitna Nemocnica Martin
- Department Name
- Klinika detskej anestéziológie a intenzívnej medicíny
- Contact Person Name
- Slavomír Nosáľ
- Contact Person Email
- slavonosal@yahoo.com
- Site Name
- Univerzitna Nemocnica Martin
- Department Name
- Neonatologická klinika
- Contact Person Name
- Lucia Časnocha Lúčanová
- Contact Person Email
- luciacasnocha@gmail.com
- Site Name
- Univerzitna Nemocnica Martin
- Department Name
- Klinika detí a dorastu, Oddelenie pediatrickej intenzívnej medicíny
- Contact Person Name
- Ján Mikler
- Contact Person Email
- miklerjan@gmail.com
- Site Name
- Národny ustav srdcovych a cievnych chorob a.s.
- Department Name
- Oddelenie anesteziológie a intenzívnej medicíny
- Contact Person Name
- Ľubica Kováčiková
- Contact Person Email
- mudr.kovacikovalubica@gmail.com
- Site Name
- Detska Fakultna Nemocnica S Poliklinikou Banska Bystrica
- Department Name
- II. Klinika pediatrickej anestéziológie a intenzívnej medicíny SZU
- Contact Person Name
- Oliver Petrík
- Contact Person Email
- oliver.petrik@dfnbb.sk
Spain
- Earliest CTIS Part Ii Submission Date
- 16-07-2025
- Latest Decision Or Authorization Date
- 03-10-2025
- Processing Time Days
- 79
- Number Of Sites
- 4
- Number Of Participants
- 4
Sites
- Site Name
- Hospital Universitario Hm Monteprincipe
- Department Name
- Pediatría
- Contact Person Name
- Silvina Laura Natalini Martínez
- Contact Person Email
- slnatalini@hmhospitales.com
- Site Name
- Hospital Universitario La Paz
- Department Name
- Pediatría, Enfermedades Infecciosas y Tropicales
- Contact Person Name
- Fernando Baquero Artigao
- Contact Person Email
- fbaqueroartigao@gmail.com
- Site Name
- Hospital Sant Joan De Deu Barcelona
- Department Name
- Infecciosas
- Contact Person Name
- Claudia Fortuny Guasch
- Contact Person Email
- claudia.fortuny@sjd.es
- Site Name
- Hospital Universitario 12 De Octubre
- Department Name
- Pediatría
- Contact Person Name
- Daniel Blázquez Gamero
- Contact Person Email
- danielblazquezgamero@gmail.com
Sponsor
Primary sponsor
- Full Name
- Pfizer Inc.
- Organisation Type
- Pharmaceutical company
- Country Of Registered Address
- United States
Contract research organisations
- Name
- Labcorp Central Laboratory Services LP
- Responsibilities
- Central laboratory services
- Name
- Labcorp Central Laboratory Services SARL
- Responsibilities
- Central laboratory services
Third parties
- {"country":"United States","full_name":"Labcorp Central Laboratory Services LP","duties_or_roles":"Central laboratory services (sponsor third party; sponsorDuties code 4)","organisation_type":"Pharmaceutical company / Laboratory services"}
- {"country":"Switzerland","full_name":"Labcorp Central Laboratory Services SARL","duties_or_roles":"Central laboratory services (sponsor third party; sponsorDuties code 4)","organisation_type":"Pharmaceutical company / Laboratory services"}
Investigational products
- Investigational Product Name
- Aztreonam and Avibactam (1.5g/0.5g) Powder for Concentrate for Solution for Infusion
- Active Substance
- Aztreonam, Avibactam sodium
- Modality
- Small molecule
- Routes Of Administration
- Intravenous infusion
- Route
- Intravenous infusion
- Authorisation Status
- 1
- Starting Dose
- IV ATM-AVI loading dose according to weight and age
- Dose Levels
- Loading dose and maintenance doses q6h or q8h according to age; minimum 3 days, maximum 14 days
- Frequency
- q6h or q8h according to age
- Maximum Dose
- 173.3 mg/kg per day
- Investigational Product Name
- Metronidazole (various formulations e.g. 500 mg / 100 ml Intravenous Infusion)
- Active Substance
- Metronidazole
- Modality
- Small molecule
- Routes Of Administration
- Intravenous
- Route
- Intravenous
- Authorisation Status
- 1/2
- Starting Dose
- Metronidazole administered IV as per investigator discretion or per combination regimen for cIAI
- Dose Levels
- As per local product and investigator decision; used in combination for cIAI where indicated
- Maximum Dose
- 40 mg/kg per day
- Combination Treatment
- Yes
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