Observational Study of Pediatric Rheumatic Diseases: The CARRA Registry

Rheumatic Joint Disease Clinical Trial

Official title:

Observational Study of Pediatric Rheumatic Diseases: The CARRA Registry

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02418442
• Other study ID #: Pro00054616
• Status: Recruiting
• Start date: July 2015
• Est. completion date: December 2028

Study information

• Verified date: October 2023
• Source: Duke University
• Contact: Mara L Becker, MD, MSCE
• Phone: (919) 419-5032
• Email: mara.becker[@]duke.edu
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20000
• Est. completion date: December 2028
• Est. primary completion date: June 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 21 Years

Eligibility

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.

Related Conditions & MeSH terms

• Collagen Diseases
• Joint Diseases
• Rheumatic Diseases
• Rheumatic Joint Disease

Locations

Country	Name	City	State
Canada	University of Calgary - Alberta Children's Hospital	Calgary	Alberta
Canada	IWK Health Center	Halifax	Nova Scotia
Canada	The Hospital for Sick Children	Toronto	Ontario
Canada	University of Manitoba - Children's Hospital of Manitoba	Winnipeg	Manitoba
Israel	Schneider Children's Medical Center of Israel	Petach Tikva
Italy	IRCCS Ospedale Pediatrico Bambino Gesu (OPBG)	Rome
Puerto Rico	San Jorge Children's Hospital	San Juan
United States	Akron Children's Hospital	Akron	Ohio
United States	Albany Medical College	Albany	New York
United States	University of Michigan	Ann Arbor	Michigan
United States	Emory Children's Center	Atlanta	Georgia
United States	Georgia Regents University Medical Center	Augusta	Georgia
United States	The Children's Hospital of Colorado	Aurora	Colorado
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Boston Children's Hospital	Boston	Massachusetts
United States	Massachusetts General Hospital for Children	Boston	Massachusetts
United States	Tufts Medical Center	Boston	Massachusetts
United States	University of Vermont Medical Center	Burlington	Vermont
United States	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina
United States	Medical University of South Carolina Children's Hospital	Charleston	South Carolina
United States	Levine Children's Hospital / Carolinas Medical Center	Charlotte	North Carolina
United States	Ann & Robert H. Lurie Children's Hospital of Chicago	Chicago	Illinois
United States	University of Chicago Medical Center	Chicago	Illinois
United States	University of Illinois at Chicago	Chicago	Illinois
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	Metrohealth Medical Center	Cleveland	Ohio
United States	UH Rainbox Babies and Children's Hospital	Cleveland	Ohio
United States	Nationwide Children's Hospital	Columbus	Ohio
United States	University of Texas Southwestern Medical Center Dallas	Dallas	Texas
United States	Duke Children's Hospital & Health Center	Durham	North Carolina
United States	Sanford Health	Fargo	North Dakota
United States	University of Florida - Shand's Children's Hospital	Gainesville	Florida
United States	Helen Devos Children's Hospital	Grand Rapids	Michigan
United States	West Michigan Rheumatology	Grand Rapids	Michigan
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	Connecticut Children's Medical Center	Hartford	Connecticut
United States	Penn State Children's Hospital	Hershey	Pennsylvania
United States	Baylor College of Medicine Pediatric Immunology Allergy Rheumatology	Houston	Texas
United States	Indiana University School of Medicine	Indianapolis	Indiana
United States	The University of Iowa Hospitals and Clinics (University of Iowa Children's Hospital)	Iowa City	Iowa
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	Children's Mercy Hospital	Kansas City	Missouri
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	Cohen Children's Medical Center of New York	Lake Success	New York
United States	Children's Hospital of Los Angeles	Los Angeles	California
United States	Mattel Children's Hospital at University of California Los Angeles	Los Angeles	California
United States	University of Louisville Schoole of Medicine	Louisville	Kentucky
United States	University of Wisconsin, American Family Children's Hospital	Madison	Wisconsin
United States	Nicklaus Children's Hospital	Miami	Florida
United States	University of Minnesota	Minneapolis	Minnesota
United States	Goryeb Children's Hospital	Morristown	New Jersey
United States	Monroe Carrell Jr. Children's Hospital at Vanderbilt	Nashville	Tennessee
United States	Robert Wood Johnson Medical School	New Brunswick	New Jersey
United States	Yale University	New Haven	Connecticut
United States	Children's Hospital at Montefiore	New York	New York
United States	Columbia University Medical Center	New York	New York
United States	Hospital for Special Surgery	New York	New York
United States	New York University Langone Medical Center	New York	New York
United States	Children's Hospital of the King's Daughters	Norfolk	Virginia
United States	Nemours Children's Hospital	Orlando	Florida
United States	Stanford University Medical Center	Palo Alto	California
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Saint Christopher's Hospital for Children	Philadelphia	Pennsylvania
United States	Phoenix Children's Hospital	Phoenix	Arizona
United States	Children's Hospital of Pittsburgh UPMC	Pittsburgh	Pennsylvania
United States	Randall Children's Hospital at Legacy Emanuel	Portland	Oregon
United States	Hasbro Children's Hospital	Providence	Rhode Island
United States	Mayo Clinic	Rochester	Minnesota
United States	University of Rochester	Rochester	New York
United States	Saint Louis Children's Hospital	Saint Louis	Missouri
United States	Saint Louis University School of Medicine	Saint Louis	Missouri
United States	Johns Hopkins All Children's Hospital	Saint Petersburg	Florida
United States	University of Utah Hospitals and Clinics (Primary Children's Hospital)	Salt Lake City	Utah
United States	Rady Children's Hospital San Diego	San Diego	California
United States	University of California at San Francisco Medical Center	San Francisco	California
United States	Seattle Children's Hospital	Seattle	Washington
United States	Bay State Medical Center	Springfield	Massachusetts
United States	Childrens National Medical Center	Washington	District of Columbia
United States	Children's Hospital Of Wisconsin	Wauwatosa	Wisconsin
United States	The Pediatric Specialty Center at Saint Barnabas	West Orange	New Jersey
United States	Wake Forest Baptist Brenner Children's Hospital	Winston-Salem	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Duke University	Childhood Arthritis and Rheumatology Research Alliance

Countries where clinical trial is conducted

United States,  Canada,  Israel,  Italy,  Puerto Rico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Prospectively collect essential data elements from children, adolescents and young adults with pediatric rheumatic diseases		Approximately 10 years
Primary	Evaluate the safety of therapeutic agents in persons with pediatric onset rheumatic diseases		Approximately 10 years
Secondary	Evaluate clinical outcomes associated with the use of therapeutic agents in persons with pediatric onset rheumatic diseases		Approximately 10 years
Secondary	Document drug treatment patterns and clinical course of persons with pediatric onset rheumatic diseases over time.		Approximately 10 years
Secondary	Evaluate factors other than drug treatments that are associated with clinical outcomes in pediatric onset rheumatic diseases		Approximately 10 years