Fosfomycin i.v. for Treatment of Severely Infected Patients

Sepsis Clinical Trial

— FORTRESS  

Official title:

An International, Multicentre, Non-comparative, Non-interventional, Prospective Clinical Registry to Evaluate the Clinical Outcome and Safety of the Treatment of Severely Infected Patients With Fosfomycin i.v.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02979951
• Other study ID #: FORTRESS
• Status: Recruiting
• Start date: December 2016
• Est. completion date: December 2030

Study information

• Verified date: February 2023
• Source: Infectopharm Arzneimittel GmbH
• Contact: Thomas Borrmann, Dr.
• Email: Clinical.Trials[@]infectopharm.com
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The purpose of this European, multicentric, prospective, non-interventional study is to document and evaluate the efficacy and safety of the treatment of severely infected patients with intravenously administered fosfomycin, including patients with osteomyelitis, complicated urinary tract infection, nosocomial lower respiratory tract infection, bacterial meningitis/central nervous system infection, bacteraemia/sepsis, skin and soft tissue infection, endocarditis or other infections, each as far as covered by the respective nationally relevant SmPC.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1000
• Est. completion date: December 2030
• Est. primary completion date: December 2030
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Male or female patients aged = 18 years

• Treatment with fosfomycin according to the (national) Summary of Product Characteristics (SmPC) of fosfomycin i.v.

• Patients with osteomyelitis, complicated urinary tract infection, nosocomial lower respiratory tract infection, bacterial meningitis/central nervous system infection, bacteraemia/sepsis, skin and soft tissue infection, endocarditis or other infection, each as far as covered by the respective nationally relevant SmPC

• Written informed consent of the participant (or person in charge in case of patients incapable of giving consent)

Exclusion Criteria:

• Previous documentation of the patient in the present study

• Patients participating in an interventional clinical trial

• Patients with known hypersensitivity to fosfomycin or any of the excipients

• Terminally ill patients

• Patients with "do not resuscitate order"

• Palliative treatment approach

• Failure of > 3 of the following organ systems: respiratory system, nervous system, cardiovascular system, liver, coagulation, kidney

• Manifest Human Immunodeficiency Virus (HIV) disease (Acquired Immunodeficiency Syndrome, AIDS)

• Fosfomycin treatment as 4th line treatment or at later stage

• Patients with involvement of fungi or mycobacteria in the targeted infection

Related Conditions & MeSH terms

• Abscess
• Bacteremia
• Bacterial Infections
• Bone Diseases
• Bone Diseases, Infectious
• Brain Abscess
• Central Nervous System Bacterial Infections
• Communicable Diseases
• Encephalitis
• Endocarditis
• Endocarditis, Bacterial
• Infections
• Intraabdominal Infections
• Meningitis
• Meningitis, Bacterial
• Osteomyelitis
• Pneumonia
• Pneumonia, Bacterial
• Respiratory Tract Infections
• Sepsis
• Skin Diseases
• Skin Diseases, Bacterial
• Soft Tissue Infections
• Urinary Tract Infections

Locations

Country	Name	City	State
Austria	Landeskrankenhaus Hall - Tirol Kliniken	Hall In Tirol
Austria	A.ö. Bezirkskrankenhaus	Reutte
Austria	Klinikum Wels-Grieskirchen, Institut für Hygiene und Mikrobiologie	Wels
Austria	AKH Wien, Universitätsklinik für Innere Medizin 1	Wien
Germany	Universitätsmedizin Charité	Berlin
Germany	Vivantes Kliniken Neukölln	Berlin
Germany	Städtisches Klinikum Braunschweig	Braunschweig
Germany	Universitäts Düsseldorf; Klinik für Anästhesiologie	Dusseldorf
Germany	Universitätsklinikum Frankfurt	Frankfurt
Germany	Universität Hamburg-Eppendorf	Hamburg
Germany	Universitätsklinikum Jena; Zentrum für Infektionsmedizin	Jena
Germany	Universitätsklinikum Schleswig-Holstein	Kiel
Germany	Universitätsklinik Schleswig-Holstein	Lübeck
Germany	LMU München	München
Germany	Universitätsklinikum Münster	Münster
Germany	Klinikum Oldenburg	Oldenburg in Holstein
Germany	Universitätsklinik Regensburg; Klinik für Anästhesiologie	Regensburg
Germany	Kliniken Nordoberpfalz	Weiden
Greece	RIO Univ. Hospital, Dept of Pathology, Division of Infectious Diseases	Patras
Italy	Clinical Malattie Infettive	Bari
Italy	Azienda Ospedaliera S.Croce e Carle	Cuneo
Italy	Ospedal Policlinico San Martino	Genova
Italy	Ospedale L. Sacco	Mailand
Italy	Istituto Mediterraneo per i Trapianti Ismett IRCCS	Palermo
Italy	Policlinico Paolo Giaccone	Palermo
Italy	Lazzaro Spallanzani	Rom
Italy	Policlinico Umberto I, Malattie Infettive	Rom
Italy	Polocinico Tor Vergata	Rom
Italy	AOU Città della Salute e Scienza-Presidio Molinette	Torino
Italy	Ospedale S.M.della Misericordia	Udine
Italy	ASST-Sette Lagh Viale Borre	Varese
United Kingdom	Royal Bolton Hospital	Bolton
United Kingdom	Hull & East Yorkshire Hospitals NHS Trust	Cottingham
United Kingdom	Ninewells Hospital	Dundee
United Kingdom	Queen Elisabeth University Hospital	Glasgow
United Kingdom	University of Glasgow/Royal Infirmary	Glasgow
United Kingdom	University Hospital Crosshouse	Kilmarnock
United Kingdom	Chelsea & Westminster Hospial	London
United Kingdom	Queen Elisabeth Hospital	London
United Kingdom	Univresity College Londen (UCL) Hospital	London

Sponsors (3)

Lead Sponsor	Collaborator
Infectopharm Arzneimittel GmbH	Dr. Oestreich + Partner GmbH, INPADS GmbH

Countries where clinical trial is conducted

Austria,  Germany,  Greece,  Italy,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of patients with clinical success as defined as clinical cure or clinical improvement	Definition of clinical cure (both criteria must be fulfilled): Resolution of signs and symptoms and; microbiological cure or no additional antibiotic therapy for the targeted infection necessary.; Definition of clinical improvement (both criteria must be fulfilled): Partial resolution of signs and symptoms and; microbiological cure or no additional antibiotic therapy for the targeted infection necessary.; Definition of microbiological cure: Elimination of the relevant pathogen(s) at the relevant site(s) of infection (at least one negative culture) or; in case "no sample available/indicated due to sufficient clinical response", pathogen elimination is considered.; Time Frame: Time point "End of fosfomycin treatment" (EOT) is reached at the day of the last fosfomycin application in the course of the treatment schedule for the targeted infection (i.e., in case of a multiple stage treatment schedule, the end of the last fosfomycin treatment phase).	Analysed at EOT ("End of fosfomycin treatment", up to 6 months after start of fosfomycin treatment)
Secondary	Microbiological cure	Definition of microbiological cure: Elimination of the relevant pathogen(s) at the relevant site(s) of infection (at least one negative culture) or; in case "no sample available/indicated due to sufficient clinical response", pathogen elimination is considered.; Time Frame: Time point "initial response" is defined to be after start of fosfomycin treatment and not later than 7 days after start of fosfomycin treatment.	Analysed at "initial response" (not later than 7 days after start of fosfomycin treatment)
Secondary	Microbiological cure	Definition of microbiological cure: Elimination of the relevant pathogen(s) at the relevant site(s) of infection (at least one negative culture) or; in case "no sample available/indicated due to sufficient clinical response", pathogen elimination is considered.; Time Frame: Time point "End of fosfomycin treatment" (EOT) is reached at the day of the last fosfomycin application in the course of the treatment schedule for the targeted infection (i.e., in case of a multiple stage treatment schedule, the end of the last fosfomycin treatment phase).	Analysed at EOT ("End of fosfomycin treatment", up to 6 months after start of fosfomycin treatment)
Secondary	Microbiological cure	Definition of microbiological cure: Elimination of the relevant pathogen(s) at the relevant site(s) of infection (at least one negative culture) or; in case "no sample available/indicated due to sufficient clinical response", pathogen elimination is considered.; Time Frame: Time point "TOC" is defined to be not earlier than EOT and not later than end of hospital stay of the patient.	Analysed at TOC ("Test of cure", up to 6 months after start of fosfomycin treatment)
Secondary	Microbiological cure	Definition of microbiological cure: Elimination of the relevant pathogen(s) at the relevant site(s) of infection (at least one negative culture) or; in case "no sample available/indicated due to sufficient clinical response", pathogen elimination is considered.; Time Frame: Defined to be after end of hospital stay + within 1 year after start of fosfomycin treatment. Either the latest visit after "End of hospital stay" within 1 year after start of fosfomycin treatment or, if applicable, the visit in this time frame assessing a clinical failure/relapse.	Analysed at follow-up (within one year after start of fosfomycin treatment) (only for indication "osteomyelitis")
Secondary	Clinical success as defined as clinical cure or clinical improvement	Definition of clinical cure (both criteria must be fulfilled): Resolution of signs and symptoms and; microbiological cure or no additional antibiotic therapy for the targeted infection necessary.; Definition of clinical improvement (both criteria must be fulfilled): Partial resolution of signs and symptoms and; microbiological cure or no additional antibiotic therapy for the targeted infection necessary.; Definition of microbiological cure: Elimination of the relevant pathogen(s) at the relevant site(s) of infection (at least one negative culture) or; in case "no sample available/indicated due to sufficient clinical response", pathogen elimination is considered.; Time Frame: Time point "initial response" is defined to be after start of fosfomycin treatment and not later than 7 days after start of fosfomycin treatment.	Analysed at "initial response" (not later than 7 days after start of fosfomycin treatment)
Secondary	Clinical success as defined as clinical cure or clinical improvement	Definition of clinical cure (both criteria must be fulfilled): Resolution of signs and symptoms and; microbiological cure or no additional antibiotic therapy for the targeted infection necessary.; Definition of clinical improvement (both criteria must be fulfilled): Partial resolution of signs and symptoms and; microbiological cure or no additional antibiotic therapy for the targeted infection necessary.; Definition of microbiological cure: Elimination of the relevant pathogen(s) at the relevant site(s) of infection (at least one negative culture) or; in case "no sample available/indicated due to sufficient clinical response", pathogen elimination is considered.; Time Frame: Time point "TOC" is defined to be not earlier than EOT and not later than end of hospital stay of the patient.	Analysed at TOC ("Test of cure", up to 6 months after start of fosfomycin treatment)
Secondary	Clinical success as defined as clinical cure or clinical improvement	Definition of clinical cure (both criteria must be fulfilled): Resolution of signs and symptoms and; microbiological cure or no additional antibiotic therapy for the targeted infection necessary.; Definition of clinical improvement (both criteria must be fulfilled): Partial resolution of signs and symptoms and; microbiological cure or no additional antibiotic therapy for the targeted infection necessary.; Definition of microbiological cure: Elimination of the relevant pathogen(s) at the relevant site(s) of infection (at least one negative culture) or; in case "no sample available/indicated due to sufficient clinical response", pathogen elimination is considered.; Time Frame: Defined to be after end of hospital stay + within 1 year after start of fosfomycin treatment. Either the latest visit after "End of hospital stay" within 1 year after start of fosfomycin treatment or, if applicable, the visit in this time frame assessing a clinical failure/relapse.	Analysed at follow-up (within one year after start of fosfomycin treatment) (only for indication "osteomyelitis")
Secondary	Clinical cure	Definition of clinical cure (both criteria must be fulfilled): Resolution of signs and symptoms and; microbiological cure or no additional antibiotic therapy for the targeted infection necessary.; Definition of microbiological cure: Elimination of the relevant pathogen(s) at the relevant site(s) of infection (at least one negative culture) or; in case "no sample available/indicated due to sufficient clinical response", pathogen elimination is considered.; Time Frame: Time point "End of fosfomycin treatment" (EOT) is reached at the day of the last fosfomycin application in the course of the treatment schedule for the targeted infection (i.e., in case of a multiple stage treatment schedule, the end of the last fosfomycin treatment phase).	Analysed at EOT ("End of fosfomycin treatment", up to 6 months after start of fosfomycin treatment)
Secondary	Clinical cure	Definition of clinical cure (both criteria must be fulfilled): Resolution of signs and symptoms and; microbiological cure or no additional antibiotic therapy for the targeted infection necessary.; Definition of microbiological cure: Elimination of the relevant pathogen(s) at the relevant site(s) of infection (at least one negative culture) or; in case "no sample available/indicated due to sufficient clinical response", pathogen elimination is considered.; Time Frame: Time point "TOC" is defined to be not earlier than EOT and not later than end of hospital stay of the patient.	Analysed at TOC ("Test of cure", up to 6 months after start of fosfomycin treatment)
Secondary	Clinical cure	Definition of clinical cure (both criteria must be fulfilled): Resolution of signs and symptoms and; microbiological cure or no additional antibiotic therapy for the targeted infection necessary.; Definition of microbiological cure: Elimination of the relevant pathogen(s) at the relevant site(s) of infection (at least one negative culture) or; in case "no sample available/indicated due to sufficient clinical response", pathogen elimination is considered.; Time Frame: Defined to be after end of hospital stay + within 1 year after start of fosfomycin treatment. Either the latest visit after "End of hospital stay" within 1 year after start of fosfomycin treatment or, if applicable, the visit in this time frame assessing a clinical failure/relapse.	Analysed at follow-up (within one year after start of fosfomycin treatment) (only for indication "osteomyelitis")
Secondary	Clinical improvement	Definition of clinical improvement (both criteria must be fulfilled): Partial resolution of signs and symptoms and; microbiological cure or no additional antibiotic therapy for the targeted infection necessary.; Definition of microbiological cure: Elimination of the relevant pathogen(s) at the relevant site(s) of infection (at least one negative culture) or; in case "no sample available/indicated due to sufficient clinical response", pathogen elimination is considered.; Time Frame: Time point "initial response" is defined to be after start of fosfomycin treatment and not later than 7 days after start of fosfomycin treatment.	Analysed at "initial response" (not later than 7 days after start of fosfomycin treatment)
Secondary	Clinical improvement	Definition of clinical improvement (both criteria must be fulfilled): Partial resolution of signs and symptoms and; microbiological cure or no additional antibiotic therapy for the targeted infection necessary.; Definition of microbiological cure: Elimination of the relevant pathogen(s) at the relevant site(s) of infection (at least one negative culture) or; in case "no sample available/indicated due to sufficient clinical response", pathogen elimination is considered.; Time Frame: Time point "End of fosfomycin treatment" (EOT) is reached at the day of the last fosfomycin application in the course of the treatment schedule for the targeted infection (i.e., in case of a multiple stage treatment schedule, the end of the last fosfomycin treatment phase).	Analysed at EOT ("End of fosfomycin treatment", up to 6 months after start of fosfomycin treatment)
Secondary	Clinical improvement	Definition of clinical improvement (both criteria must be fulfilled): Partial resolution of signs and symptoms and; microbiological cure or no additional antibiotic therapy for the targeted infection necessary.; Definition of microbiological cure: Elimination of the relevant pathogen(s) at the relevant site(s) of infection (at least one negative culture) or; in case "no sample available/indicated due to sufficient clinical response", pathogen elimination is considered.; Time Frame: Time point "TOC" is defined to be not earlier than EOT and not later than end of hospital stay of the patient.	Analysed at TOC ("Test of cure", up to 6 months after start of fosfomycin treatment)
Secondary	Clinical improvement	Definition of clinical improvement (both criteria must be fulfilled): Partial resolution of signs and symptoms and; microbiological cure or no additional antibiotic therapy for the targeted infection necessary.; Definition of microbiological cure: Elimination of the relevant pathogen(s) at the relevant site(s) of infection (at least one negative culture) or; in case "no sample available/indicated due to sufficient clinical response", pathogen elimination is considered.; Time Frame: Defined to be after end of hospital stay + within 1 year after start of fosfomycin treatment. Either the latest visit after "End of hospital stay" within 1 year after start of fosfomycin treatment or, if applicable, the visit in this time frame assessing a clinical failure/relapse.	Analysed at follow-up (within one year after start of fosfomycin treatment) (only for indication "osteomyelitis")
Secondary	Sodium serum levels		On every day from start of fosfomycin treatment until end of hospital stay (up to 6 months after start of fosfomycin treatment)
Secondary	Potassium serum levels		On every day from start of fosfomycin treatment until end of hospital stay (up to 6 months after start of fosfomycin treatment)
Secondary	Adverse events		On every day from start of fosfomycin treatment until end of follow-up (up to one year after start of fosfomycin treatment)
Secondary	Non-serious adverse events		On every day from start of fosfomycin treatment until end of follow-up (up to one year after start of fosfomycin treatment)
Secondary	Serious adverse events		On every day from start of fosfomycin treatment until end of follow-up (up to one year after start of fosfomycin treatment)
Secondary	Cases of death		On every day from start of fosfomycin treatment until end of follow-up (up to one year after start of fosfomycin treatment)
Secondary	Adverse drug reactions (ADRs)		On every day from start of fosfomycin treatment until end of follow-up (up to one year after start of fosfomycin treatment)
Secondary	Serious adverse drug reactions (SADRs)		On every day from start of fosfomycin treatment until end of follow-up (up to one year after start of fosfomycin treatment)
Secondary	Dropouts due to treatment failure or due to adverse events		On every day from start of fosfomycin treatment until end of follow-up (up to one year after start of fosfomycin treatment)