The EPIC Observational Study - Full Text View

Sponsor:	CF Therapeutics Development Network Coordinating Center
Collaborator:	Cystic Fibrosis Foundation
Information provided by (Responsible Party):	CF Therapeutics Development Network Coordinating Center
ClinicalTrials.gov Identifier:	NCT00676169

Purpose

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.

Condition
Cystic Fibrosis

Study Type:	Observational
Study Design:	Observational Model: Cohort Time Perspective: Prospective
Official Title:	Longitudinal Assessment of Risk Factors For and Impact of Pseudomonas Aeruginosa Acquisition and Early Anti-Pseudomonal Treatment in Children With CF

Resource links provided by NLM:

Genetics Home Reference related topics: cystic fibrosis

MedlinePlus related topics: Cystic Fibrosis

U.S. FDA Resources

Further study details as provided by CF Therapeutics Development Network Coordinating Center:

Primary Outcome Measures:

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. [ Time Frame: over the two-to-five-year observational period ] [ Designated as safety issue: No ]
To better define clinical outcomes associated with acquisition of Pa, as well as outcomes associated with emergence of mucoid Pa and antibiotic-resistant Pa. [ Time Frame: over the two-to-five-year observational period ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

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. [ Time Frame: over the two-to-five year observational period ] [ Designated as safety issue: No ]
To describe temporal changes in anti-pseudomonal serology and airway microbiology. [ Time Frame: over the two-to-five year observational period ] [ Designated as safety issue: No ]
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). [ Time Frame: over the two-to-five year observational period ] [ Designated as safety issue: No ]
To bank Pa and S. aureus isolates and serum samples for future studies to enhance the understanding of early CF lung disease. [ Time Frame: over the two-to-five year observational period ] [ Designated as safety issue: No ]
To use and bank DNA samples for analyses of genetic factors that may be associated with CF pathogenesis, disease progression, and clinical outcomes. [ Time Frame: over the two-to-five year observational period ] [ Designated as safety issue: No ]
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. [ Time Frame: over the two-to-five year observational period ] [ Designated as safety issue: No ]
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. [ Time Frame: over the two-to-five year observational period ] [ Designated as safety issue: No ]

Biospecimen Retention: Samples With DNA

For study purposes, OP swabs or expectorated sputum for bacterial culture will be obtained annually beginning in the calendar year of first isolation of Pa from a respiratory culture at the local site laboratory. A serum sample for serology assessment and banking will be obtained annually in conjunction with a scheduled clinical blood draw whenever possible. Under a separate consent, additional blood (6 ml) will be collected for DNA use and banking for studies of genetic factors that may be associated with CF pathogenesis, disease progression, and clinical outcomes. These studies will test for association between gene variants and various CF-related phenotypes using either a targeted (i.e., candidate gene) approach or by performing a whole-genome scan.

Estimated Enrollment:	1700
Study Start Date:	October 2004
Estimated Study Completion Date:	May 2014
Estimated Primary Completion Date:	March 2014 (Final data collection date for primary outcome measure)

Groups/Cohorts
Observational Pa negative or concurrently enrolled in the EPIC Clinical Trial

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

Ages Eligible for Study:	up to 12 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No
Sampling Method:	Non-Probability Sample

Study Population

Children with Cystic Fibrosis who are Pa negative or concurrently enrolled in the EPIC Clinical Trial

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00676169

Show 54 Study Locations

Sponsors and Collaborators

CF Therapeutics Development Network Coordinating Center

Cystic Fibrosis Foundation

Investigators

Principal Investigator:	Margaret Rosenfeld, MD, MPH	Seattle Children's Hospital
Principal Investigator:	Ronald L. Gibson, MD, PhD	Seattle Children's Hospital
Principal Investigator:	Wayne J. Morgan, MD	University of Arizona Health Sciences Center

More Information

No publications provided by CF Therapeutics Development Network Coordinating Center

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

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. Epub 2009 Jan 15.

Responsible Party:	CF Therapeutics Development Network Coordinating Center
ClinicalTrials.gov Identifier:	NCT00676169 History of Changes
Other Study ID Numbers:	EPIC002
Study First Received:	May 8, 2008
Last Updated:	December 13, 2011
Health Authority:	United States: Institutional Review Board

Keywords provided by CF Therapeutics Development Network Coordinating Center:

Pseudomonas aeruginosa
EPIC

Additional relevant MeSH terms:

Cystic Fibrosis
Fibrosis
Pancreatic Diseases
Digestive System Diseases
Lung Diseases

Respiratory Tract Diseases
Genetic Diseases, Inborn
Infant, Newborn, Diseases
Pathologic Processes

ClinicalTrials.gov processed this record on February 12, 2012