Clinical trial NCT02418442: Observational Study of Pediatric Rheumatic Diseases: The CARRA Registry
Official title: Observational Study of Pediatric Rheumatic Diseases: The CARRA Registry
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Rheumatic Joint Disease
Keywords: Systemic Arthritis
Oligoarthritis
Polyarthritis (Rheumatoid Factor Negative)
Polyarthritis (Rheumatoid Factor Positive)
Psoriatic Arthritis
Enthesitis Related Arthritis (ERA)
Undifferianted Arthritis
CARRA Consensus Treatment Plans
Lead sponsor: Duke University
Sponsor class: OTHER
Collaborators: name: Childhood Arthritis and Rheumatology Research Alliance
First posted: 2015-04-16
Enrollment: 20000
Sex: ALL
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Children with pediatric rheumatic diseases enrolled from participating CARRA sites.

Brief summary: Continuation of the CARRA Registry as described in the protocol will support data collection on patients with pediatric-onset rheumatic diseases. The CARRA Registry will form the basis for future CARRA studies. In particular, this observational registry will be used to answer pressing questions about therapeutics used to treat pediatric rheumatic diseases, including safety questions.

Detailed description: The original Childhood Arthritis \& Rheumatology Research Alliance (CARRA) Registry (Protocol Number: CRNT_REGST01) was first established in 2010 to advance alliance infrastructure, facilitate expanded clinical and translational pediatric research, and transform the culture of pediatric rheumatology toward universal participation in research. This original CARRA Registry will be referred to throughout the protocol as the CARRA Legacy Registry. Through the creation of a sophisticated informatics infrastructure, provision of comprehensive site support and the engagement of families, patients, and communities, the CARRA Registry will provide the opportunity for affected children at every CARRA Registry site to participate in high-quality clinical and translational research.

Continuation of the CARRA Registry as described in this protocol will support data collection on patients with pediatric-onset rheumatic diseases. The CARRA Registry will form the basis for future CARRA studies. In particular, this observational registry will be used to answer pressing questions about therapeutics used to treat pediatric rheumatic diseases, including examining safety questions. The Duke Clinical Research Institute (DCRI) is serving as the CARRA Clinical and Data Coordinating Center (CDCC) for the protocol.

Traditional exposure-based post-marketing registries of individual therapeutic agents for juvenile idiopathic arthritis (JIA), systemic lupus erythematosus, and other rheumatic diseases are inadequate for answering important safety questions for many reasons:

* Sample sizes are too small to detect uncommon but important events
* No unexposed comparators exist to evaluate risk attributable to underlying disease
* Duration of follow-up of individual patients is too short to evaluate many potential delayed adverse events (AEs)
* Sample sizes are inadequate to assess myriad complex and dynamic concurrent medication regimens common to treatment of rheumatic diseases
* Selective patient enrollment limits evaluation of co-morbid conditions and other patient factors

These limitations prevent patients, families, and providers from understanding the true risks and benefits of therapy in order to make appropriate and informed decisions. They also prevent drug manufacturers and regulatory agencies from conducting an informed review of marketed products for these diseases.

A registry based on disease diagnosis rather than specific therapeutic agents overcomes many of the limitations of exposure-based single-agent registries in the assessment of delayed or uncommon safety events. Indeed, data from a consolidated disease-based registry "...could provide the information necessary for individual companies to satisfy post-marketing requirements and commitments and obviate the need for an individual product registry" (letters from the United States (US) Food and Drug Administration (FDA) to CARRA, 21 December 2010 and 9 December 2011). This protocol details the foundation of a registry to meet these objectives.

The CARRA Registry aims to detect and understand the epidemiology of important AEs, including those that are delayed or uncommon. Subjects followed at active CARRA Registry sites are eligible for enrollment, regardless of past or current treatment. Each subject will be followed prospectively for a goal of 10 years duration; the study will continue indefinitely as resources allow and continued need exists. Data will be systematically collected, including important patient factors, therapies, serious adverse events (SAEs), and protocol-defined events of special interest. Selected safety events (e.g., malignancies) will be adjudicated by a panel of experts via a review of medical records. The CARRA Registry, a disease-based prospective observational registry, enables both detection of potential safety signals and hypothesis-driven, rigorous, and adequately-controlled pharmacoepidemiologic studies of important AEs and their associations with therapeutic agents.

In addition to answering questions about the safety of therapeutics, the data collected in the CARRA Registry are anticipated to serve many other valuable uses. Within the confines of observational study design, the effectiveness of therapeutic agents may be examined for short- and long-term clinical and patient-centered outcomes.

The Registry is the data collection platform for Consensus Treatment Plan (CTP) comparative effectiveness research in pediatric rheumatic disease. Patients enrolled in the Registry may also be eligible to be followed as part of a CTP subset. Examples of CTP projects include:

FiRst line Options for Systemic JIA Treatment (FROST). The purpose of FROST was to compare the effectiveness of CARRA systemic JIA (sJIA) treatment strategies (biologic vs. non-biologic) in achieving clinically inactive disease in patients with new-onset sJIA. Additionally, FROST aimed to compare patient/caregiver reported outcomes between treatment strategies. FROST enrolled new-onset, previously untreated sJIA patients who are starting treatment with one of the 4 sJIA CTPs (glucocorticoid (GC) only; Methotrexate + GC; IL-1 inhibitor + GC; IL-6 + GC). Enrollment will occur over 3 years at all CARRA Registry sites. In addition to routine Registry data collection, patients followed as part of the FROST CTP completed additional questionnaires about their disease status and quality of life.

Medication use for pediatric rheumatic diseases is dynamic and not well characterized. The CARRA Registry represents a powerful data source to follow drug use patterns and provides the opportunity to study predictors of medication use. Important outcomes are likely to be influenced by other factors in addition to therapy (e.g., disease severity) and the CARRA Registry is positioned to help answer these types of questions. Patient-reported outcomes (PROs) generated by patients outside the context of clinical encounters may be collected in the Registry to provide a rich, additional dimension of data to better understand rheumatic diseases. Practitioners may review clinical data from their sites as part of a quality improvement approach to better outcomes.

Analyses of CARRA Registry data aim to provide results to guide the therapeutic decisions made by affected children, families, and providers while improving regulatory efficiency and reducing cost. Ultimately, this approach might serve as a model for successful collaboration between research community networks, industry, and public agencies to promote the effective and efficient evaluation of drugs and devices across the regulatory continuum.

Eligibility criteria: Inclusion Criteria:

1. Onset of rheumatic disease prior to age 16 years for JIA and onset prior to age 19 years for all other rheumatic diseases (see appendix A).
2. Subject (and/or parent/legal guardian when required) is able to provide written informed consent and willing to comply with study procedures.
3. Subject and/or parent/legal guardian is willing to be contacted in the future by study staff.

Exclusion Criteria:

1. Greater than 21 years of age at the time of enrollment.

Primary outcomes:
measure: Prospectively collect essential data elements from children, adolescents and young adults with pediatric rheumatic diseases
timeFrame: Approximately 10 years
measure: Evaluate the safety of therapeutic agents in persons with pediatric onset rheumatic diseases
timeFrame: Approximately 10 years
Secondary outcomes:
measure: Evaluate clinical outcomes associated with the use of therapeutic agents in persons with pediatric onset rheumatic diseases
timeFrame: Approximately 10 years
measure: Document drug treatment patterns and clinical course of persons with pediatric onset rheumatic diseases over time.
timeFrame: Approximately 10 years
measure: Evaluate factors other than drug treatments that are associated with clinical outcomes in pediatric onset rheumatic diseases
timeFrame: Approximately 10 years
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Phoenix
country: United States
facility: Phoenix Children's Hospital
state: Arizona
city: Los Angeles
country: United States
facility: Children's Hospital of Los Angeles
state: California
city: Los Angeles
country: United States
facility: Mattel Children's Hospital at University of California Los Angeles
state: California
city: Palo Alto
country: United States
facility: Stanford University Medical Center
state: California
city: San Diego
country: United States
facility: Rady Children's Hospital San Diego
state: California
city: San Francisco
country: United States
facility: University of California at San Francisco Medical Center
state: California
city: Aurora
country: United States
facility: The Children's Hospital of Colorado
state: Colorado
city: Hartford
country: United States
facility: Connecticut Children's Medical Center
state: Connecticut
city: New Haven
country: United States
facility: Yale University
state: Connecticut
city: Washington
country: United States
facility: Childrens National Medical Center
state: District of Columbia
city: Gainesville
country: United States
facility: University of Florida - Shand's Children's Hospital
state: Florida
city: Miami
country: United States
facility: Nicklaus Children's Hospital
state: Florida
city: Orlando
country: United States
facility: Nemours Children's Hospital
state: Florida
city: Saint Petersburg
country: United States
facility: Johns Hopkins All Children's Hospital
state: Florida
city: Atlanta
country: United States
facility: Emory Children's Center
state: Georgia
city: Augusta
country: United States
facility: Georgia Regents University Medical Center
state: Georgia
city: Chicago
country: United States
facility: University of Illinois at Chicago
state: Illinois
city: Chicago
country: United States
facility: Ann & Robert H. Lurie Children's Hospital of Chicago
state: Illinois
city: Chicago
country: United States
facility: University of Chicago Medical Center
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University School of Medicine
state: Indiana
city: Iowa City
country: United States
facility: The University of Iowa Hospitals and Clinics (University of Iowa Children's Hospital)
state: Iowa
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Louisville
country: United States
facility: University of Louisville Schoole of Medicine
state: Kentucky
city: Boston
country: United States
facility: Tufts Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Massachusetts General Hospital for Children
state: Massachusetts
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
city: Springfield
country: United States
facility: Bay State Medical Center
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Grand Rapids
country: United States
facility: Helen Devos Children's Hospital
state: Michigan
city: Grand Rapids
country: United States
facility: West Michigan Rheumatology
state: Michigan
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic
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: Saint Louis University School of Medicine
state: Missouri
city: Saint Louis
country: United States
facility: Saint Louis Children's Hospital
state: Missouri
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: Morristown
country: United States
facility: Goryeb Children's Hospital
state: New Jersey
city: New Brunswick
country: United States
facility: Robert Wood Johnson Medical School
state: New Jersey
city: West Orange
country: United States
facility: The Pediatric Specialty Center at Saint Barnabas
state: New Jersey
city: Albany
country: United States
facility: Albany Medical College
state: New York
city: Lake Success
country: United States
facility: Cohen Children's Medical Center of New York
state: New York
city: New York
country: United States
facility: New York University Langone Medical Center
state: New York
city: New York
country: United States
facility: Hospital for Special Surgery
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: New York
country: United States
facility: Children's Hospital at Montefiore
state: New York
city: Rochester
country: United States
facility: University of Rochester
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill
state: North Carolina
city: Charlotte
country: United States
facility: Levine Children's Hospital / Carolinas Medical Center
state: North Carolina
city: Durham
country: United States
facility: Duke Children's Hospital & Health Center
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest Baptist Brenner Children's Hospital
state: North Carolina
city: Fargo
country: United States
facility: Sanford Health
state: North Dakota
city: Akron
country: United States
facility: Akron Children's Hospital
state: Ohio
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Cleveland
country: United States
facility: UH Rainbox Babies and Children's Hospital
state: Ohio
city: Cleveland
country: United States
facility: Metrohealth Medical Center
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Portland
country: United States
facility: Randall Children's Hospital at Legacy Emanuel
state: Oregon
city: Hershey
country: United States
facility: Penn State Children's Hospital
state: Pennsylvania
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Philadelphia
country: United States
facility: Saint Christopher's Hospital for Children
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Children's Hospital of Pittsburgh UPMC
state: Pennsylvania
city: Providence
country: United States
facility: Hasbro Children's Hospital
state: Rhode Island
city: Charleston
country: United States
facility: Medical University of South Carolina Children's Hospital
state: South Carolina
city: Nashville
country: United States
facility: Monroe Carrell Jr. Children's Hospital at Vanderbilt
state: Tennessee
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center Dallas
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine Pediatric Immunology Allergy Rheumatology
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah Hospitals and Clinics (Primary Children's Hospital)
state: Utah
city: Burlington
country: United States
facility: University of Vermont Medical Center
state: Vermont
city: Norfolk
country: United States
facility: Children's Hospital of the King's Daughters
state: Virginia
city: Seattle
country: United States
facility: Seattle Children's Hospital
state: Washington
city: Madison
country: United States
facility: University of Wisconsin, American Family Children's Hospital
state: Wisconsin
city: Wauwatosa
country: United States
facility: Children's Hospital Of Wisconsin
state: Wisconsin
city: Calgary
country: Canada
facility: University of Calgary - Alberta Children's Hospital
state: Alberta
city: Winnipeg
country: Canada
facility: University of Manitoba - Children's Hospital of Manitoba
state: Manitoba
city: Halifax
country: Canada
facility: IWK Health Center
state: Nova Scotia
city: Toronto
country: Canada
facility: The Hospital for Sick Children
state: Ontario
city: Petach Tikva
country: Israel
facility: Schneider Children's Medical Center of Israel
city: Rome
country: Italy
facility: IRCCS Ospedale Pediatrico Bambino Gesu (OPBG)
city: San Juan
country: Puerto Rico
facility: San Jorge Children's Hospital
Study officials:
affiliation: Duke Clinical Research Insitute
name: Mara L Becker, MD, MSCE
role: PRINCIPAL_INVESTIGATOR
affiliation: Boston Children's Hospital
name: Mary Beth Son, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Alabama at Birmingham
name: Timothy Beukelman, MD, MSCE
role: PRINCIPAL_INVESTIGATOR
References:
citation: Nigrovic PA, Beukelman T, Tomlinson G, Feldman BM, Schanberg LE, Kimura Y; Childhood Arthritis and Rheumatology Research Alliance Systemic Juvenile Idiopathic Arthritis Consensus Treatment Plan Workgroup. Bayesian comparative effectiveness study of four consensus treatment plans for initial management of systemic juvenile idiopathic arthritis: FiRst-Line Options for Systemic juvenile idiopathic arthritis Treatment (FROST). Clin Trials. 2018 Jun;15(3):268-277. doi: 10.1177/1740774518761367. Epub 2018 Mar 15.