Treatments Against RA and Effect on FDG-PET/CT

NCT ID: NCT02374021

Last Updated: 2022-10-26

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

159 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-07-31

Study Completion Date

2021-05-31

Brief Summary

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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).

Detailed Description

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Consenting subjects will be screened for eligibility and randomized to a treatment arm. Subjects will be randomized to a treatment arm with either synthetic disease-modifying antirheumatic drugs (DMARDs) \[triple therapy: sulfasalazine, methotrexate, and hydroxychloroquine\] or biologic DMARDs \[etanercept or adalimumab, plus background methotrexate for all subjects and hydroxychloroquine for subjects who were taking this at screening\].

Once randomized, a baseline visit will be conducted with each subject. Baseline data collection includes questionnaires, disease activity score, and the first FDG-PET/CT imaging. After the baseline at week 0, subjects will visit with their rheumatologist at weeks 6, 12, 18, and 24 for safety labs and further collection of disease activity scores and questionnaires. The second FDG-PET/CT will be performed at week 24. Blood specimens will be collected at weeks 0, 6, 18, and 24 for bioassays. Subject participation will end after the week 24 visit.

Patients and care providers will be unblinded. The FDG-PET/CT image readers will be blinded to treatment arm as well as timepoint of image acquisition.

Conditions

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Arthritis, Rheumatoid

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Outcome Assessors

Study Groups

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Triple therapy (MTX+SSZ+HCQ)

Sulfasalazine (SSZ) 1 g bid and hydroxychloroquine (HCQ) 200 mg twice daily, not to exceed 6.5mg/kg HCQ (in addition to concomitant methotrexate \[MTX\]).

Group Type ACTIVE_COMPARATOR

Methotrexate

Intervention Type DRUG

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.

Sulfasalazine

Intervention Type DRUG

1 gm bid

Hydroxychloroquine

Intervention Type DRUG

200 mg twice daily, not to exceed 6.5mg/kg

TNF inhibitor (etanercept or adalimumab)

etanercept 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.

Group Type ACTIVE_COMPARATOR

Methotrexate

Intervention Type DRUG

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.

Etanercept

Intervention Type DRUG

50 mg SC weekly

Adalimumab

Intervention Type DRUG

40 mg SQ every other week

Interventions

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Methotrexate

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.

Intervention Type DRUG

Sulfasalazine

1 gm bid

Intervention Type DRUG

Hydroxychloroquine

200 mg twice daily, not to exceed 6.5mg/kg

Intervention Type DRUG

Etanercept

50 mg SC weekly

Intervention Type DRUG

Adalimumab

40 mg SQ every other week

Intervention Type DRUG

Other Intervention Names

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Rheumatrex Azulfidine Plaquenil enbrel Humira

Eligibility Criteria

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Inclusion Criteria

* 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

Exclusion Criteria

* 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
* 2 or more high dose radiation scans in the past year (CT scan with contrast, angiogram, SPECT nuclear medicine scan, myocardial/cardiac perfusion scan)
Minimum Eligible Age

45 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Columbia University

OTHER

Sponsor Role collaborator

Brigham and Women's Hospital

OTHER

Sponsor Role lead

Responsible Party

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Daniel H. Solomon, M.D.,MPH

Chief, Section of Clinical Sciences

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Daniel Solomon

Role: PRINCIPAL_INVESTIGATOR

Brigham and Women's Hospital

Locations

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University of Alabama at Birmingham

Birmingham, Alabama, United States

Site Status

Loma Linda University Clinical Trial Center

Loma Linda, California, United States

Site Status

David Geffen School of Medicine at UCLA

Los Angeles, California, United States

Site Status

Brigid Freyne, MD Inc.

Murrieta, California, United States

Site Status

Desert Medical Advances

Palm Desert, California, United States

Site Status

University of California San Francisco

San Francisco, California, United States

Site Status

Nazanin Firooz MD, Inc.

West Hills, California, United States

Site Status

Robert W. Levin, MD, PA

Clearwater, Florida, United States

Site Status

IRIS Research and Development

Plantation, Florida, United States

Site Status

Southwest Florida Clinical Research Center

Tampa, Florida, United States

Site Status

University of Kentucky

Lexington, Kentucky, United States

Site Status

The Center for Rheumatology and Bone Research

Wheaton, Maryland, United States

Site Status

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status

Brigham and Women's Hospital

Boston, Massachusetts, United States

Site Status

University of Michigan

Ann Arbor, Michigan, United States

Site Status

Washington University Medical Center

St Louis, Missouri, United States

Site Status

Dartmouth-Hitchcock Medical Center

Lebanon, New Hampshire, United States

Site Status

Northwell Health

Great Neck, New York, United States

Site Status

New York University School of Medicine

New York, New York, United States

Site Status

Mount Sinai- Icahn School of Medicine

New York, New York, United States

Site Status

Columbia University Medical Center

New York, New York, United States

Site Status

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, United States

Site Status

Cleveland Clinic

Cleveland, Ohio, United States

Site Status

Oregon Health & Science University

Portland, Oregon, United States

Site Status

Altoona Research Center

Duncansville, Pennsylvania, United States

Site Status

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Site Status

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, United States

Site Status

Metroplex Clinical Research Center

Dallas, Texas, United States

Site Status

University of Texas Health Science Center at Houston

Houston, Texas, United States

Site Status

Baylor Scott & White Medical Center- Temple

Temple, Texas, United States

Site Status

Seattle Rheumatology Associates

Seattle, Washington, United States

Site Status

Countries

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United States

References

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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.

Reference Type DERIVED
PMID: 38915065 (View on PubMed)

Solomon 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.

Reference Type DERIVED
PMID: 36450449 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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2014P002747

Identifier Type: -

Identifier Source: org_study_id

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