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Observational Study of Pediatric Rheumatic Diseases: The CARRA Registry

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ClinicalTrials.gov Identifier: NCT02418442
Recruitment Status : Recruiting
First Posted : April 16, 2015
Last Update Posted : September 9, 2022
Sponsor:
Collaborator:
Childhood Arthritis and Rheumatology Research Alliance
Information provided by (Responsible Party):
Duke University

Tracking Information
First Submitted Date April 13, 2015
First Posted Date April 16, 2015
Last Update Posted Date September 9, 2022
Study Start Date July 2015
Estimated Primary Completion Date June 2028   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: April 13, 2015)
  • Prospectively collect essential data elements from children, adolescents and young adults with pediatric rheumatic diseases [ Time Frame: Approximately 10 years ]
  • Evaluate the safety of therapeutic agents in persons with pediatric onset rheumatic diseases [ Time Frame: Approximately 10 years ]
Original Primary Outcome Measures Same as current
Change History
Current Secondary Outcome Measures
 (submitted: April 13, 2015)
  • Evaluate clinical outcomes associated with the use of therapeutic agents in persons with pediatric onset rheumatic diseases [ Time Frame: Approximately 10 years ]
  • Document drug treatment patterns and clinical course of persons with pediatric onset rheumatic diseases over time. [ Time Frame: Approximately 10 years ]
  • Evaluate factors other than drug treatments that are associated with clinical outcomes in pediatric onset rheumatic diseases [ Time Frame: Approximately 10 years ]
Original Secondary Outcome Measures Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title Observational Study of Pediatric Rheumatic Diseases: The CARRA Registry
Official Title Observational Study of Pediatric Rheumatic Diseases: The CARRA Registry
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.

Study Type Observational [Patient Registry]
Study Design Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration 10 Years
Biospecimen Retention:   Samples With DNA
Description:
Biosample collection is active for a subset of subjects within the registry
Sampling Method Non-Probability Sample
Study Population Children with pediatric rheumatic diseases enrolled from participating CARRA sites.
Condition Rheumatic Joint Disease
Intervention Not Provided
Study Groups/Cohorts Not Provided
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Recruiting
Estimated Enrollment
 (submitted: April 28, 2020)
20000
Original Estimated Enrollment
 (submitted: April 13, 2015)
10000
Estimated Study Completion Date December 2028
Estimated Primary Completion Date June 2028   (Final data collection date for primary outcome measure)
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.

Sex/Gender
Sexes Eligible for Study: All
Ages up to 21 Years   (Child, Adult)
Accepts Healthy Volunteers No
Contacts
Contact: Mara L Becker, MD, MSCE (919) 419-5032 mara.becker@duke.edu
Contact: Mary Beth Son, MD (617) 919-6083 marybeth.son@childrens.harvard.edu
Listed Location Countries Canada,   Israel,   Italy,   Puerto Rico,   United States
Removed Location Countries  
 
Administrative Information
NCT Number NCT02418442
Other Study ID Numbers Pro00054616
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement Not Provided
Current Responsible Party Duke University
Original Responsible Party Same as current
Current Study Sponsor Duke University
Original Study Sponsor Same as current
Collaborators Childhood Arthritis and Rheumatology Research Alliance
Investigators
Principal Investigator: Mara L Becker, MD, MSCE Duke Clinical Research Insitute
Principal Investigator: Mary Beth Son, MD Boston Children's Hospital
Principal Investigator: Timothy Beukelman, MD, MSCE University of Alabama at Birmingham
PRS Account Duke University
Verification Date September 2022