Treatments Against RA and Effect on FDG-PET/CT
TARGET
1 other identifier
interventional
159
1 country
31
Brief Summary
In a randomized controlled clinical trial, investigators will compare the effects on \[18F\]-fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET/CT) from two treatment regimens in rheumatoid arthritis (RA) patients deemed methotrexate inadequate responders (MTX-IRs). Two common RA treatments will be compared: triple therapy (sulfasalazine, methotrexate, and hydroxychloroquine) versus tumor necrosis factor (TNF) inhibitor (etanercept or adalimumab, plus background methotrexate for all subjects and hydroxychloroquine for subjects who were taking this at screening).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_4
Started Jul 2016
Longer than P75 for phase_4
31 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
February 11, 2015
CompletedFirst Posted
Study publicly available on registry
February 27, 2015
CompletedStudy Start
First participant enrolled
July 1, 2016
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 1, 2021
CompletedStudy Completion
Last participant's last visit for all outcomes
May 1, 2021
CompletedResults Posted
Study results publicly available
October 26, 2022
CompletedOctober 26, 2022
October 1, 2022
4.8 years
February 11, 2015
July 26, 2022
October 25, 2022
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Change From Baseline in Vascular Inflammation as Measured by FDG-PET/CT at 6 Months
The primary outcome was the change in the mean of the maximum of the target to background ratio (TBR) in the most diseased segment (MDS) of of the index vessel as measured by FDG-PET/CT scans conducted at baseline and after 24 weeks of randomized treatment allocation (MDS meanmaxTBR). The index vessel is the vessel (either aorta, left carotid, or right carotid) with the highest meanmaxTBR at baseline. Higher values indicate greater vascular inflammation. FDG uptake measurement: PET-CT images were batch-analyzed by an investigator blinded to the patients' clinical information. FDG uptake was evaluated within the wall of the ascending aorta and bilateral carotid arteries (as maximum and mean standardized FDG uptake value \[SUVmax and SUVmean, respectively\]) approximately every 5 mm on axial images. Subsequently, the target-to-background ratio (TBR) was reported (ratio of the average arterial to blood axial slice SUVmax) to correct for the blood compartment contribution.
0, 6 months
Secondary Outcomes (4)
Change From Baseline in the MDS of the Aorta
0, 6 months
Change From Baseline in the Average TBR of the Aorta
0, 6 months
Change From Baseline in the Average TBR of the Bilateral Carotids
0, 6 months
Change From Baseline in the Average TBR of the Index Vessel
0, 6 months
Study Arms (2)
Triple therapy (MTX+SSZ+HCQ)
ACTIVE COMPARATORSulfasalazine (SSZ) 1 g bid and hydroxychloroquine (HCQ) 200 mg twice daily, not to exceed 6.5mg/kg HCQ (in addition to concomitant methotrexate \[MTX\]).
TNF inhibitor (etanercept or adalimumab)
ACTIVE COMPARATORetanercept 50 mg subcutaneously weekly or adalimumab 40 mg subcutaneously every other week (in addition to concomitant methotrexate, plus hydroxychloroquine, for subjects who were taking this at screening). Biologic treatment will be assigned randomly.
Interventions
Subjects entering trial will continue on MTX dose of at least 15mg MTX/week. At the discretion of the treating rheumatologist, may be switched to SQ route.
200 mg twice daily, not to exceed 6.5mg/kg
40 mg SQ every other week
Eligibility Criteria
You may qualify if:
- Fulfill American College of Rheumatology/European League Against Rheumatism 2010 criteria for RA
- Men ≥ 45 years and women ≥ 50 years
- MTX monotherapy for ≥ 8 weeks at ≥ 15mg weekly or ≥ 7.5 mg weekly with a documented intolerance to higher doses
- No non-biologic DMARDs in preceding two months (other than MTX and HCQ)
- Disease Activity Score-28 \> 3.2
- Able to sign informed consent
You may not qualify if:
- Use of biologic DMARD within the past 6 months or use of rituximab ever
- Current use of \>10mg per day of prednisone
- Use of a high-intensity statin lipid lowering drug or PCSK9 inhibitor in the past 12 months
- Prior patient reported, physician diagnosed clinical cardiovascular (CV) event
- Insulin-dependent or uncontrolled diabetes mellitus (DM)
- Systemic lupus erythematosus (SLE) or other autoimmune and chronic inflammatory diseases (i.e. inflammatory bowel disease, sarcoidosis)
- Cancer treated in the last 5 years (except basal and squamous cell) or any lymphoma or melanoma
- Known pregnancy, HIV, Hepatitis B Virus, Hepatitis C Virus, active (or untreated latent) tuberculosis
- Baseline: liver, renal or blood count abnormalities, Glucose-6-phosphate dehydrogenase (G6PD) deficiency
- Known sulfa allergy, macular disease or hypersensitivity to treatments; known demyelinating disease; uncompensated Congestive Heart Failure (CHF)
- Intra-articular injection within the 4 weeks prior to baseline FDG PET/CT
- or more high dose radiation scans in the past year (CT scan with contrast, angiogram, SPECT nuclear medicine scan, myocardial/cardiac perfusion scan)
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Brigham and Women's Hospitallead
- Columbia Universitycollaborator
Study Sites (31)
University of Alabama at Birmingham
Birmingham, Alabama, 35294, United States
Loma Linda University Clinical Trial Center
Loma Linda, California, 92354, United States
David Geffen School of Medicine at UCLA
Los Angeles, California, 90095, United States
Brigid Freyne, MD Inc.
Murrieta, California, 92563, United States
Desert Medical Advances
Palm Desert, California, 92260, United States
University of California San Francisco
San Francisco, California, 94110, United States
Nazanin Firooz MD, Inc.
West Hills, California, 91307, United States
Robert W. Levin, MD, PA
Clearwater, Florida, 33765, United States
IRIS Research and Development
Plantation, Florida, 33324, United States
Southwest Florida Clinical Research Center
Tampa, Florida, 33609, United States
University of Kentucky
Lexington, Kentucky, 40508, United States
The Center for Rheumatology and Bone Research
Wheaton, Maryland, 20902, United States
Massachusetts General Hospital
Boston, Massachusetts, 02114, United States
Brigham and Women's Hospital
Boston, Massachusetts, 02115, United States
University of Michigan
Ann Arbor, Michigan, 48109, United States
Washington University Medical Center
St Louis, Missouri, 63110, United States
Dartmouth-Hitchcock Medical Center
Lebanon, New Hampshire, 03756, United States
Northwell Health
Great Neck, New York, 11021, United States
New York University School of Medicine
New York, New York, 10003, United States
Mount Sinai- Icahn School of Medicine
New York, New York, 10029, United States
Columbia University Medical Center
New York, New York, 10032, United States
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, 27599, United States
Cleveland Clinic
Cleveland, Ohio, 44195, United States
Oregon Health & Science University
Portland, Oregon, 97329, United States
Altoona Research Center
Duncansville, Pennsylvania, 16635, United States
University of Pennsylvania
Philadelphia, Pennsylvania, 19104, United States
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, 15261, United States
Metroplex Clinical Research Center
Dallas, Texas, 75231, United States
University of Texas Health Science Center at Houston
Houston, Texas, 77030, United States
Baylor Scott & White Medical Center- Temple
Temple, Texas, 76508, United States
Seattle Rheumatology Associates
Seattle, Washington, 98122, United States
Related Publications (2)
Liao KP, Rist P, Giles J, Santacroce L, Connelly MA, Glynn RJ, Ridker P, Tawakol A, Bathon J, Solomon DH. Impact of RA treatment strategies on lipids and vascular inflammation in rheumatoid arthritis: a secondary analysis of the TARGET randomized active comparator trial. Arthritis Res Ther. 2024 Jun 24;26(1):123. doi: 10.1186/s13075-024-03352-3.
PMID: 38915065DERIVEDSolomon DH, Giles JT, Liao KP, Ridker PM, Rist PM, Glynn RJ, Broderick R, Lu F, Murray MT, Vanni K, Santacroce LM, Abohashem S, Robson PM, Fayad Z, Mani V, Tawakol A, Bathon J; TARGET Trial Consortium. Reducing cardiovascular risk with immunomodulators: a randomised active comparator trial among patients with rheumatoid arthritis. Ann Rheum Dis. 2023 Mar;82(3):324-330. doi: 10.1136/ard-2022-223302. Epub 2022 Nov 30.
PMID: 36450449DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Dr. Daniel Solomon
- Organization
- Brigham and Women's Hospital
Study Officials
- PRINCIPAL INVESTIGATOR
Daniel Solomon
Brigham and Women's Hospital
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- No
Study Design
- Study Type
- interventional
- Phase
- phase 4
- Allocation
- RANDOMIZED
- Masking
- SINGLE
- Who Masked
- OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Chief, Section of Clinical Sciences
Study Record Dates
First Submitted
February 11, 2015
First Posted
February 27, 2015
Study Start
July 1, 2016
Primary Completion
May 1, 2021
Study Completion
May 1, 2021
Last Updated
October 26, 2022
Results First Posted
October 26, 2022
Record last verified: 2022-10