Start Time Optimization of Biologics in Polyarticular JIA

NCT ID: NCT02593006

Last Updated: 2021-02-05

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 400 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2015-11-30
• Study Completion Date: 2019-09-30

Brief Summary

STOP-JIA is a PCORI funded prospective observational study which compared the clinical effectiveness and impact on patient reported outcomes of 3 Childhood Arthritis & Rheumatology Research Alliance (CARRA) consensus derived treatment strategies (CTPs) in new-onset polyarticular JIA (pJIA) patients to answer the critical question of when is the best time to begin biologic medications to achieve the optimal clinical and patient reported outcomes. Because the CARRA Registry will be used for data collection, all patients will be enrolled in the CARRA Registry. The standard of care treatments are chosen by the treating physician and patient/caregiver and are not randomized.

Detailed Description

STOP-JIA is a prospective, observational study comparing the clinical effectiveness and impact on patient reported outcomes of 3 different treatment strategies (CTPs) in new onset pJIA patients to answer the critical question of when to start biologic medications. All participants will be enrolled in the CARRA Registry and started on one of the CTPs, which will be decided by the treating physician and patient/caregiver. Subjects will be enrolled at one of 60 participating CARRA sites across the US and Canada. Total anticipated enrollment was 400 and this was completed in 9/19.

Specific Aim 1:

To compare the clinical effectiveness of different strategies (CTPs) for using biologic medications in achieving clinically inactive disease (CID) at 12 months in new-onset pJIA. Three common strategies that differ in the timing of biologic medication introduction will be compared: 1) Step-Up: disease modifying anti-rheumatic drug (DMARD) monotherapy stepping up by addition of a biologic medication if needed; 2) Early Combination: DMARD plus biologic medication at treatment onset; and 3) Biologic First: biologic medication monotherapy at treatment onset.

Hypothesis 1: A significantly higher proportion of children started on a biologic medication at onset (CTP 2 or 3) will achieve CID after 12 months of therapy compared to standard therapy (CTP 1).

Specific Aim 2:

To compare patient and caregiver reported outcomes between the different strategies.

Hypothesis 2: There will be statistically significant differences in patient/caregiver reported outcomes (PROs) between treatment strategies that can inform future patients and providers in selecting optimal treatments.

The CARRA Registry will be housed at CARRA's clinical and data coordinating center, Duke Clinical Research Institute (DCRI). The CARRA Registry Protocol documents that the CARRA Registry fulfills all PCOR standards for registries. STOP-JIA will utilize data collection, storage, and management processes, systems requirements, and security processes already established for the CARRA Registry at DCRI.

STOP-JIA used Web-based electronic CRFs (eCRFs) developed for the CARRA Registry that are already familiar to site personnel. The eCRF platform, RAVE, is 21CFR part11 compliant and meets regulatory requirements. Database and Web servers are secured by a firewall and through controlled physical access. eCRFs will be monitored for completeness, accuracy, and attention to detail throughout the study by DCRI data and site management teams using processes developed for the CARRA Registry and consistent with DCRI's internal SOPs. Use of electronic data capture will allow for immediate prompts/queries if entered values are out of expected ranges or there are incomplete data fields. The design of the data collection instrument will allow centers to record a planned assessment of a patient was missed and to enter any known reasons for the assessment being missed. DCRI will regularly provide reports detailing data completion metrics to the sites. Stakeholder engagement is also an important aspect of this study, and patients/caregivers as well as other stakeholders are serving as research partners and advisors in this study.

Conditions

Polyarticular Juvenile Rheumatoid Arthritis; Arthritis, Juvenile Idiopathic

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Eligibility Criteria

Inclusion Criteria

• Age less than 19 at baseline (if 18 or older, agrees to be followed for at least one year)
• Diagnosis of Arthritis per ACR definition.
• Arthritis present in one joint for a least six weeks
• At least 5 active joints at baseline
• Contraception if sexually active (male and female)

May have any of the following:

• RF+ polyarticular JIA
• RF- polyarticular JIA
• Extended oligoarticular JIA
• Psoriatic JIA
• Enthesitis related JIA
• Undifferentiated JIA
• Psoriasis
• Sacroiliitis
• Uveitis
• Enthesitis
• Prior treatments permitted:

• NSAIDS
• Hydroxychloroquine
• Intraocular / topical / intraarticular glucocorticoids
• IV or PO steroids if one of the below criteria are met:

--If treated ≤ 3 months prior to baseline: treatment cannot exceed 2 weeks

--If treated > 3 months prior to baseline: any treatment course is permitted as long as treatment was completed 90 days prior to baseline

• Methotrexate started no more than 1 month prior to the baseline visit
• Biologics - received only 1 dose within 1 week of the baseline visit

Exclusion Criteria

• Features consistent with systemic JIA
• Treatment with any medications for JIA aside from those listed above.
• Known inflammatory bowel disease
• Known celiac disease
• Known Trisomy 21
• History of or current malignancy
• Concomitant serious active or recurrent chronic bacterial, fungal or viral infection
• Significant organ system disorder limiting use of treatments for pJIA
• Live vaccine within a month prior to baseline

• Minimum Eligible Age: 2 Years
• Maximum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Patient-Centered Outcomes Research Institute

OTHER

Sponsor Role: collaborator

Childhood Arthritis and Rheumatology Research Alliance

OTHER

Sponsor Role: collaborator

Duke Clinical Research Institute

OTHER

Sponsor Role: collaborator

Seattle Children's Hospital

OTHER

Sponsor Role: collaborator

Children's Hospital of Philadelphia

OTHER

Sponsor Role: collaborator

Boston Children's Hospital

OTHER

Sponsor Role: collaborator

The Hospital for Sick Children

OTHER

Sponsor Role: collaborator

University Health Network, Toronto

OTHER

Sponsor Role: collaborator

Hackensack Meridian Health

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Yukiko Kimura, MD

Role: PRINCIPAL_INVESTIGATOR

Hackensack Meridian Health

Sarah Ringold, MD

Role: PRINCIPAL_INVESTIGATOR

Seattle Children's Hospital

Locations

University of Alabama at Birmingham

Birmingham, Alabama, United States

Stanford University Medical Center

Palo Alto, California, 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

Children's Hospital Colorado

Aurora, Colorado, United States

Connecticut Children's Medical Center

Hartford, Connecticut, United States

University of Florida Shand's Children's Hospital

Gainesville, Florida, United States

Emory Children's Center

Atlanta, Georgia, United States

Georgia Regents University Medical Center

Augusta, Georgia, United States

Ann & Robert H. Lurie Children's Hospital of Chicago

Chicago, Illinois, United States

University of Chicago Medical Center

Chicago, Illinois, United States

Indiana University School of Medicine

Indianapolis, Indiana, United States

University of Iowa Hospitals and Clinics

Iowa City, Iowa, United States

University of Kansas Medical Center

Kansas City, Kansas, United States

University of Louisville School of Medicine

Louisville, Kentucky, United States

Tufts Medical Center

Boston, Massachusetts, United States

Boston Children's Hospital

Boston, Massachusetts, United States

Baystate Medical Center, High Street Health Center

Springfield, Massachusetts, United States

University of Michigan Medical Center

Ann Arbor, Michigan, United States

University of Minnesota

Minneapolis, Minnesota, United States

Mayo Clinic

Rochester, Minnesota, United States

Children's Mercy Hospital

Kansas City, Missouri, United States

Saint Louis University School of Medicine

St Louis, Missouri, United States

Saint Louis Children's Hospital

St Louis, Missouri, United States

HackensackUniversity Medical Center

Hackensack, New Jersey, United States

Goryeb Children's Hospital

Morristown, New Jersey, United States

Pediatric Specialty Center at Saint Barnabas

West Orange, New Jersey, United States

Albany Medical College

Albany, New York, United States

Cohen Children's Medical Center of New York

Lake Success, New York, United States

New York University Langone Medical Center

New York, New York, United States

Hospital for Special Surgery

New York, New York, United States

Columbia University Medical Center

New York, New York, United States

Children's Hospital at Montefiore

The Bronx, New York, United States

Levine Children's Hospital

Charlotte, North Carolina, United States

Duke Children's Hospital & Health Center

Durham, North Carolina, United States

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

MetroHealth Medical Center

Cleveland, Ohio, United States

UH Rainbow Babies and Children's Hospital

Cleveland, Ohio, United States

Clevland Clinic Foundation

Cleveland, Ohio, United States

Nationwide Children's Hospital

Columbus, Ohio, United States

Randall Children's Hospital at Legacy Emanuel

Portland, Oregon, United States

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

St. Christopher's Hospital for Children

Philadelphia, Pennsylvania, United States

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, United States

Medical University of South Carolina Children's Hospital

Charleston, South Carolina, United States

Monroe Carell Jr. Children's Hospital at Vanderbilt

Nashville, Tennessee, United States

University of Texas Southwestern Medical Center Dallas

Dallas, Texas, United States

Baylor College of Medicine Pediatric Immunology, Allergy and Rheumatology

Houston, Texas, United States

University of Utah Hospitals and Clinics

Salt Lake City, Utah, United States

University of Vermont Medical Center

Burlington, Vermont, United States

Seattle Children's Hospital

Seattle, Washington, United States

University of Wisconsin-American Family Children's Hospital

Madison, Wisconsin, United States

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

Countries

United States; Canada

References

Kimura Y, Schanberg LE, Tomlinson GA, Riordan ME, Dennos AC, Del Gaizo V, Murphy KL, Weiss PF, Natter MD, Feldman BM, Ringold S; CARRA STOP-JIA Investigators. Optimizing the Start Time of Biologics in Polyarticular Juvenile Idiopathic Arthritis: A Comparative Effectiveness Study of Childhood Arthritis and Rheumatology Research Alliance Consensus Treatment Plans. Arthritis Rheumatol. 2021 Oct;73(10):1898-1909. doi: 10.1002/art.41888. Epub 2021 Sep 3.

Reference Type: DERIVED

PMID: 34105312 (View on PubMed)

Ong MS, Ringold S, Kimura Y, Schanberg LE, Tomlinson GA, Natter MD; CARRA Registry Investigators. Improved Disease Course Associated With Early Initiation of Biologics in Polyarticular Juvenile Idiopathic Arthritis: Trajectory Analysis of a Childhood Arthritis and Rheumatology Research Alliance Consensus Treatment Plans Study. Arthritis Rheumatol. 2021 Oct;73(10):1910-1920. doi: 10.1002/art.41892. Epub 2021 Aug 27.

Reference Type: DERIVED

PMID: 34105303 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

https://www.clinicaltrials.gov/ct2/show/NCT02418442?term=carra&rank=2

Click here for more information on the Observational Study of Pediatric Rheumatic Diseases: The CARRA Registry

Other Identifiers

Pro5835

Identifier Type: -

Identifier Source: org_study_id