The EPIC Observational Study

Study Overview
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Brief Summary
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The purpose of this study is to better define risk factors preceding first isolation of Pseudomonas aeruginosa (Pa) from respiratory cultures in cystic fibrosis (CF) lung disease and to better define clinical outcomes associated with acquisition of Pa. This study will also collect and bank DNA samples for current and future studies designed to enhance the understanding of the pathogenesis of CF.

Detailed Description
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The EPIC Observational Study is a longitudinal, prospective, observational study that was originally conducted at 59 sites. The current five-year extension study is being conducted at 54 sites. The EPIC Observational Study will serve as a freestanding epidemiologic study of the risk factors for and clinical impact of initial Pa acquisition and anti-pseudomonal therapy. Defining the risk factors for Pa acquisition can potentially allow for preventive measures and identification of high-risk populations requiring closer monitoring. Despite rigorous data collection, previous studies have been limited by small sample sizes and by conduct at one or two centers. This study will include a much larger sample size from many more centers than previous studies. It will thus provide for more generalizable results and more precise risk estimates for previously identified risk factors for Pa acquisition, and it will allow for exploration of novel risk factors not included in earlier studies. Better understanding of the clinical outcomes associated with Pa acquisition and the outcomes associated with different types of anti-pseudomonal therapies will inform the development of rational early intervention treatment regimens. Better knowledge about temporal relationships between respiratory signs and symptoms, Pa serology, and CF airway microbiology may lead to improved strategies for early detection of Pa and could have important implications for the timing of interventions aimed at preventing or treating early Pa acquisition. Finally, this study will serve as an important source of Pa and S. aureus isolates, serum samples, and DNA samples that will be used and banked for studies designed to enhance the understanding of the pathogenesis of CF, e.g., microarray investigations of early Pa isolates, investigations to identify proteomic biomarkers of airway inflammation, and investigations to identify genetic factors related to CF disease progression, including early lung disease, and clinical outcomes.

Official Title
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Longitudinal Assessment of Risk Factors For and Impact of Pseudomonas Aeruginosa Acquisition and Early Anti-Pseudomonal Treatment in Children With CF

Conditions
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Cystic Fibrosis

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female ages less than or equal to 12 years. Diagnosis of CF based upon the criteria established by the 1997 CF Consensus Conference: (i) sweat chloride > 60 mEq/L by quantitative pilocarpine iontophoresis; or (ii) genotype with two identifiable mutations consistent with CF; or (iii) an abnormal nasal transepithelial potential difference, and (iv) one or more clinical features consistent with CF. No prior isolation of Pa from respiratory cultures (1 or more cultures in 24 months prior to enrollment), or, if prior isolation of Pa from respiratory cultures, at least a two-year history of Pa negative cultures (1 or more cultures/year), or concurrently enrolled in the EPIC Clinical Trial. Signed informed consent to participate in data submission to the CFF National Patient Registry. Signed informed consent by parent or legal guardian.

Ages Eligible for Study
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Maximum Age: 12 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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Observational<br>Pa negative or concurrently enrolled in the EPIC Clinical Trial | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To better define risk factors for first isolation of Pa from respiratory culture, as well as for emergence of mucoid Pa and antibiotic-resistant Pa. |  | over the two-to-five-year observational period | 
| To better define clinical outcomes associated with acquisition of Pa, as well as outcomes associated with emergence of mucoid Pa and antibiotic-resistant Pa. |  | over the two-to-five-year observational period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Among subjects who acquire Pa but do not enroll in the EPIC Clinical Trial, to examine the effect of the duration of Pa positive respiratory cultures prior to initiation of anti-pseudomonal therapy and the type and length of anti-pseudomonal therapy. |  | over the two-to-five year observational period | 
| To describe temporal changes in anti-pseudomonal serology and airway microbiology. |  | over the two-to-five year observational period | 
| To better define clinical outcomes associated with isolation of S. aureus from respiratory cultures, as well as outcomes associated with emergence of methicillin-resistant S. aureus (MRSA). |  | over the two-to-five year observational period | 
| To bank Pa and S. aureus isolates and serum samples for future studies to enhance the understanding of early CF lung disease. |  | over the two-to-five year observational period | 
| To use and bank DNA samples for analyses of genetic factors that may be associated with CF pathogenesis, disease progression, and clinical outcomes. |  | over the two-to-five year observational period | 
| For subjects who enroll in EPIC Clinical Trial, to collect ancillary data on risk factors preceding trial enrollment and to provide follow-up for clinical endpoints after trial participation has ended. |  | over the two-to-five year observational period | 
| To provide a cohort of subjects who acquire Pa during the observational study period but who do not enroll in EPIC Clinical Trial and therefore receive non protocol-based anti-pseudomonal therapy. |  | over the two-to-five year observational period | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pseudomonas aeruginosa, EPIC