Clinical trial NCT00676169: The EPIC Observational Study
Official title: Longitudinal Assessment of Risk Factors For and Impact of Pseudomonas Aeruginosa Acquisition and Early Anti-Pseudomonal Treatment in Children With CF
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Cystic Fibrosis
Keywords: Pseudomonas aeruginosa
EPIC
Lead sponsor: CF Therapeutics Development Network Coordinating Center
Sponsor class: NETWORK
Collaborators: name: Cystic Fibrosis Foundation
First posted: 2008-05-12
Enrollment: 1248
Sex: ALL
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Children with Cystic Fibrosis who are Pa negative or concurrently enrolled in the EPIC Clinical Trial

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: 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.
timeFrame: over the two-to-five-year observational period
measure: To better define clinical outcomes associated with acquisition of Pa, as well as outcomes associated with emergence of mucoid Pa and antibiotic-resistant Pa.
timeFrame: over the two-to-five-year observational period
Secondary outcomes:
measure: 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.
timeFrame: over the two-to-five year observational period
measure: To describe temporal changes in anti-pseudomonal serology and airway microbiology.
timeFrame: over the two-to-five year observational period
measure: 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).
timeFrame: over the two-to-five year observational period
measure: To bank Pa and S. aureus isolates and serum samples for future studies to enhance the understanding of early CF lung disease.
timeFrame: over the two-to-five year observational period
measure: To use and bank DNA samples for analyses of genetic factors that may be associated with CF pathogenesis, disease progression, and clinical outcomes.
timeFrame: over the two-to-five year observational period
measure: 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.
timeFrame: over the two-to-five year observational period
measure: 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.
timeFrame: over the two-to-five year observational period
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: The University of Alabama at Birmingham
state: Alabama
city: Los Angeles
country: United States
facility: Children's Hospital of Los Angeles / USC Medical School
state: California
city: Oakland
country: United States
facility: Kaiser Permanente Medical Center
state: California
city: Palo Alto
country: United States
facility: Packard Children's Hosp., Stanford University
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: Denver
country: United States
facility: Children's Hospital Denver
state: Colorado
city: Wilmington
country: United States
facility: duPont Hospital for Children
state: Delaware
city: Jacksonville
country: United States
facility: Nemours Children's Clinic
state: Florida
city: Saint Petersburg
country: United States
facility: All Children's Hospital CF Center
state: Florida
city: Atlanta
country: United States
facility: Emory University, Cystic Fibrosis Center
state: Georgia
city: Augusta
country: United States
facility: Medical College of Georgia
state: Georgia
city: Chicago
country: United States
facility: Children's Memorial Hospital
state: Illinois
city: Indianapolis
country: United States
facility: Riley Hospital, Indiana University
state: Indiana
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
city: Lexington
country: United States
facility: University of Kentucky
state: Kentucky
city: Portland
country: United States
facility: Maine Medical Center
state: Maine
city: Boston
country: United States
facility: Children's Hospital, Boston
state: Massachusetts
city: Worcester
country: United States
facility: University of Mass Memorial Health Care
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Detroit
country: United States
facility: Children's Hospital of Michigan
state: Michigan
city: Grand Rapids
country: United States
facility: Spectrum Health Hospitals - DeVos Children's Hospital
state: Michigan
city: Minneapolis
country: United States
facility: Children's Hospitals & Clinics
state: Minnesota
city: Jackson
country: United States
facility: University of Mississippi Medical Center
state: Mississippi
city: Kansas City
country: United States
facility: Children's Mercy Hospital
state: Missouri
city: Saint Louis
country: United States
facility: Cardinal Glennon Children's Hospital - St. Louis University
state: Missouri
city: Saint Louis
country: United States
facility: Washington University School of Medicine/St. Louis Children's Hospital
state: Missouri
city: Omaha
country: United States
facility: University of Nebraska
state: Nebraska
city: Lebanon
country: United States
facility: Dartmouth-Hitchcock Medical Center
state: New Hampshire
city: Long Branch
country: United States
facility: Monmouth Medical Center
state: New Jersey
city: Albany
country: United States
facility: Albany Medical College
state: New York
city: Buffalo
country: United States
facility: Women & Children's Hospital of Buffalo
state: New York
city: New Hyde Park
country: United States
facility: Schneider Children's Hospital
state: New York
city: Rochester
country: United States
facility: University of Rochester
state: New York
city: Syracuse
country: United States
facility: SUNY Upstate Medical Center
state: New York
city: Valhalla
country: United States
facility: New York Medical College/Westchester Medical Center
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina, Chapel Hill
state: North Carolina
city: Akron
country: United States
facility: Children's Hospital Medical Center of Akron
state: Ohio
city: Cleveland
country: United States
facility: Rainbow Babies & Childrens Hospital
state: Ohio
city: Columbus
country: United States
facility: Children's Hospital
state: Ohio
city: Dayton
country: United States
facility: Children's Medical Center
state: Ohio
city: Portland
country: United States
facility: Oregon Health Sciences University
state: Oregon
city: Hershey
country: United States
facility: Penn State Milton S. Hershey Medical Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: St. Christopher's Hospital for Children
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Children's Hospital of Pittsburgh
state: Pennsylvania
city: Providence
country: United States
facility: Rhode Island Hospital
state: Rhode Island
city: Memphis
country: United States
facility: LeBonheur Children's Medical Center
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Fort Worth
country: United States
facility: Cook Children's Medical Center
state: Texas
city: Houston
country: United States
facility: Texas Children's Hospital
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Burlington
country: United States
facility: Vermont Children's Hospital at Fletcher Allen Health Care
state: Vermont
city: Seattle
country: United States
facility: Children's Hospital & Regional Medical Center
state: Washington
city: Madison
country: United States
facility: University of Wisconsin Hospital and Clinics
state: Wisconsin
city: Milwaukee
country: United States
facility: Children's Hospital of Wisconsin
state: Wisconsin
Study officials:
affiliation: Seattle Children's Hospital
name: Margaret Rosenfeld, MD, MPH
role: PRINCIPAL_INVESTIGATOR
affiliation: Seattle Children's Hospital
name: Ronald L. Gibson, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Arizona Health Sciences Center
name: Wayne J. Morgan, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Rosenfeld M, Emerson J, McNamara S, Thompson V, Ramsey BW, Morgan W, Gibson RL; EPIC Study Group. Risk factors for age at initial Pseudomonas acquisition in the cystic fibrosis epic observational cohort. J Cyst Fibros. 2012 Sep;11(5):446-53. doi: 10.1016/j.jcf.2012.04.003. Epub 2012 May 1.
citation: Rosenfeld M, Emerson J, McNamara S, Joubran K, Retsch-Bogart G, Graff GR, Gutierrez HH, Kanga JF, Lahiri T, Noyes B, Ramsey B, Ren CL, Schechter M, Morgan W, Gibson RL; EPIC Study Group Participating Clinical Sites. Baseline characteristics and factors associated with nutritional and pulmonary status at enrollment in the cystic fibrosis EPIC observational cohort. Pediatr Pulmonol. 2010 Sep;45(9):934-44. doi: 10.1002/ppul.21279.
citation: Treggiari MM, Rosenfeld M, Mayer-Hamblett N, Retsch-Bogart G, Gibson RL, Williams J, Emerson J, Kronmal RA, Ramsey BW; EPIC Study Group. Early anti-pseudomonal acquisition in young patients with cystic fibrosis: rationale and design of the EPIC clinical trial and observational study'. Contemp Clin Trials. 2009 May;30(3):256-68. doi: 10.1016/j.cct.2009.01.003. Epub 2009 Jan 15.