Fosfomycin i.v. for Treatment of Severely Infected Patients

Study Overview
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Brief Summary
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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.

Official Title
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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.

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

Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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) | 
| 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) | 
| 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) | 
| 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) | 
| 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) | 
| 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) | 
| 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) | 
| 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) | 
| 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) | 
| 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) | 
| 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) | 
| 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) | 
| 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) | 
| 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) | 
| 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) | 
| 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) | 
| Adverse events |  | On every day from start of fosfomycin treatment until end of follow-up (up to one year after start of fosfomycin treatment) | 
| 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) | 
| 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) | 
| 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) | 
| 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) | 
| 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) | 
| 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) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Observational Study, Non-Interventional Study, Registries, Prospective, Monitored, Multicentric, International, Fosfomycin, Infectofos, Fomicyt, Bacterial Infections, Osteomyelitis, Central Nervous System Bacterial Infections, Meningitis, Bacterial, Encephalitis, Brain Abscess, Urinary Tract Infections, Respiratory Tract Infections, Pneumonia, Bacterial, Skin Diseases, Bacterial, Soft Tissue Infections, Intraabdominal Infections, Bacteremia, Endocarditis, Bacterial, Treatment Outcome, Clinical Efficacy, Microbiological Efficacy, Safety, Gram-Negative Bacterial Infections, Gram-Positive Bacterial Infections, Bone Diseases, Infectious, Sepsis