RA-PRO PRAGMATIC TRIAL

Study Purpose

The 2021 ACR RA treatment guideline, based on widely acknowledged low to moderate quality evidence, recommends switching to a non-tumor necrosis factor (TNFi) biologic (choose among existing medications, currently, rituximab, abatacept, tocilizumab, or sarilumab) or a targeted synthetic DMARD arm (tsDMARD; choose among existing medications, currently, tofacitinib, baricitinib, upadacitinib) in patients with active RA despite the use of a TNFi-biologic. In practice, most patients receive another TNFi-biologic, i.e., a second TNFi-biologic first. This is not based on solid evidence, but on arbitrary algorithms often proposed by health insurance plans, and/or physician experience and habit (TNFis launched 22 yrs ago vs.#46; the first tsDMARD 8 years ago vs.#46; first non-TNF-biologic launched 17 years ago). This study will fill a critical knowledge gap by generating CER data for important PROs between these treatment options, switching to a non-TNFi biologic or a tsDMARD in patients with active RA despite the use of a TNFi-biologic.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 18 Years and Over
Gender All
More Inclusion & Exclusion Criteria

Inclusion Criteria:

1. Patients with active, disabling RA (CDAI ≥10 and HAQ ≥0.5) despite the use/experience for ≥ 3 months of a TNFi-biologic OR discontinued the medication(s) due to intolerability or toxicity irrespective of treatment duration prior to the first dose of study drug ; 2. If receiving glucocorticoids (≤10 mg/day of prednisone of equivalent) or NSAIDs, on stable doses for ≥2 weeks prior to randomization; and. 3. Insurance plan or patient assistance program allows access to at least 1 drug in each of the two treatment strategies, TNFi-biologic vs. tsDMARD. Participants will be allowed to continue their conventional synthetic DMARD (csDMARD) therapy if they had been using it for ≥ 3 months and on a stable dose for ≥ 4 weeks prior to the first dose of study drug. The following csDMARDs are allowed: methotrexate (MTX), sulfasalazine, hydroxychloroquine, and leflunomide (TNFi-biologic and tsDMARD) through insurance plan or a patient assistance program/plan.

Exclusion Criteria:

1. Prior treatment with more than three biologics, defined as TNFi-biologic or non-TNFi biologic. 2. Prior treatment with targeted synthetic DMARD. 3. Concomitant use of leflunomide, sulfasalazine, cyclosporine, or azathioprine within 2-months before randomization; 4. History of sensitivity to all 4 non-TNF-biologic or a targeted synthetic DMARD; 5. Glucocorticoid injection (intravenous, intramuscular, or intraarticular) within 1 month of study entry; 6. Live vaccine within 90 days of study entry; 7. Acute or chronic infections with parenteral antibiotics or hospitalization (including tuberculosis, bacterial sepsis; invasive fungal infections (such as histoplasmosis)) within 1 month or oral antibiotics within 2 weeks of study entry; 8. History of HIV or any opportunistic infection; 9. New York Heart Association Class III or IV heart failure; 10. Latent TB for which anti-tubercular treatment has not been started; 11. Untreated Hepatitis B or C infection; 12. History of deep venous thrombosis or pulmonary embolism; or. 13. Pregnant or nursing women; or. 14. History of herpes zoster or shingles.

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT04692493
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase 3
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

University of Alabama at Birmingham
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

Jasvinder Singh, MD
Principal Investigator Affiliation University of Alabama at Birmingham
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

Other
Overall Status Recruiting
Countries Canada, United States
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Rheumatoid Arthritis
Additional Details

Treatment of RA with a non-TNFi biologic (rituximab, abatacept, tocilizumab, or sarilumab) was associated with improved function, quality of life, and productivity. TsDMARDs (tofacitinib, baricitinib, upadacitinib) were similarly effective. No meaningful differences were noted in non-TNFi-biologic vs.#46; tsDMARD, but head-to-head studies of biologics are lacking. HAQ is a sensitive outcome for RA trials. A PCORI systematic review for early RA treatment concluded that "Evidence was insufficient to evaluate any differences between biologics for their impact on either functional capacity or HRQOL", a key knowledge gap our study will fill. The 2021 ACR RA treatment guideline, based on widely acknowledged low to moderate quality evidence, recommends switching to a non-TNFi biologic or a tsDMARD in patients with active RA despite the use of a TNFi-biologic. In practice, most patients receive another TNFi-biologic first, i.e., a second TNFi. This is not based on solid evidence, but on arbitrary algorithms often proposed by health insurance plans, and physician experience (first TNFi launched 22 yrs ago vs.#46; the first tsDMARD 8 yrs ago vs.#46; first non-TNF-biologic launched 17 years ago). This study will fill a critical knowledge gap by generating CER data for important PROs between these treatment options. This will facilitate informed decision-making, since PROs may be more sensitive to different mechanisms of action, and are highly relevant to patients. The proposed study will also provide needed evidence for real-world treatment decisions made by public and private payers. This head-to-head pragmatic trial will be the first to provide CER data for improvement in key PROs with recommended strategies in active RA despite the use of a TNFi-biologic and addresses PCORI and IOM priority areas by comparing the two most commonly used RA treatment strategies for people with active RA despite the use of a TNFi-biologic. This research is patient-centered, as study outcomes were identified by patients and payers. Currently, treatment choices are based on physician experience and insurance payer limitations. Investigators will generate evidence to help patients make decisions for themselves based on outcomes they care most about based on the relative efficacy of outcomes. Investigators will:

  • (1) compare improvements in PROs with RA treatment strategies to each other using a state-of-the-art real-world pragmatic effectiveness study design, which will for the first time include most RA patients with comorbidities;(2) compare their toxicity in a real-world population for TNFi-biologic vs.#46; tsDMARD.
To our knowledge, no previous RCT comparing these drugs has examined a PRO as a primary outcome in RA, which our study will pioneer by using HAQ. HAQ is sensitive to change with effective treatments.

Arms & Interventions

Arms

Active Comparator: targeted synthetic DMARD class

Switching to a targeted synthetic DMARD (choice from targeted synthetic DMARDs; currently available are tofacitinib, baricitinib, upadacitinib) in people with active RA despite current treatment

Active Comparator: non-TNFi-biologic class

Switching to a non-TNFi-biologic (choice from non-TNFi-biologics; currently available are rituximab, abatacept, tocilizumab, or sarilumab) in people with active RA despite current treatment,

Interventions

Drug: - targeted synthetic DMARD class

Switching to a targeted synthetic DMARD (choice from targeted synthetic DMARDs; currently available are tofacitinib, baricitinib, upadacitinib) in people with active RA despite current treatment

Drug: - non-TNFi-biologic class

Switching to a non-TNFi-biologic (choice from non-TNFi-biologics; currently available are rituximab, abatacept, tocilizumab, or sarilumab) in people with active RA despite current treatment,

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

East Alabama Arthritis Center PC, Auburn, Alabama

Status

Recruiting

Address

East Alabama Arthritis Center PC

Auburn, Alabama, 36830

Site Contact

Adahli Massey, MD

[email protected]

334-501-4424

Bendcare, LLC, Birmingham, Alabama

Status

Recruiting

Address

Bendcare, LLC

Birmingham, Alabama, 35244

Site Contact

Howard Busch, MD

[email protected]

205-975-2405

University of Alabama at Birmingham, Birmingham, Alabama

Status

Recruiting

Address

University of Alabama at Birmingham

Birmingham, Alabama, 35294

Site Contact

Rouhin Sen

[email protected]

205-275-2405

SunValley Arthritis Center, Ltd, Peoria, Arizona

Status

Recruiting

Address

SunValley Arthritis Center, Ltd

Peoria, Arizona, 85381

Site Contact

Joy Schectman, MD

[email protected]

623-566-3350

University of Arizona, Tucson, Arizona

Status

Recruiting

Address

University of Arizona

Tucson, Arizona, 85724

Site Contact

Kent C Kwoh, MD

[email protected]

205-975-2405

Pacific Arthritis Care Center, Los Angeles, California

Status

Recruiting

Address

Pacific Arthritis Care Center

Los Angeles, California, 90045

Site Contact

Dan Furst, MD

[email protected]

205-975-2405

University of California, Los Angeles, Los Angeles, California

Status

Recruiting

Address

University of California, Los Angeles

Los Angeles, California, 90095

Site Contact

Veena K. Ranganath, MD

[email protected]

205-975-2405

Arthritis Medical Center, Nipomo, California

Status

Recruiting

Address

Arthritis Medical Center

Nipomo, California, 93444

Site Contact

Frank Scott, M/D

[email protected]

805-473-4001

Turlock Arthritis & Osteoporosis Center,, Turlock, California

Status

Recruiting

Address

Turlock Arthritis & Osteoporosis Center,

Turlock, California, 95382

Site Contact

Iraj Sabahi, M/D

[email protected]

209-634-3898

Center for Rheumatology Research, Woodland Hills, California

Status

Recruiting

Address

Center for Rheumatology Research

Woodland Hills, California, 91364

Site Contact

Lauren Jackson

[email protected]

818-598-0000

George Munoz MD, PC, Aventura, Florida

Status

Recruiting

Address

George Munoz MD, PC

Aventura, Florida, 33180

Site Contact

George Munoz, MD

[email protected]

305-682-1441

Clearwater, Florida

Status

Recruiting

Address

American Arthritis and Rheumatology Associates LLC

Clearwater, Florida, 33765

Site Contact

Robert Levin, MD

[email protected]

727-734-6631

CZ Rheumatology, Coral Springs, Florida

Status

Recruiting

Address

CZ Rheumatology

Coral Springs, Florida, 33065

Site Contact

Conrad Ziembinski, MD

[email protected]

954-341-5034

Fort Lauderdale, Florida

Status

Recruiting

Address

American Arthritis and Rheumatology Associates LLC

Fort Lauderdale, Florida, 33309

Site Contact

Yvonne Sherrar, MD

[email protected]

954-229-7030

Mayo Clinic Jacksonville, Jacksonville, Florida

Status

Recruiting

Address

Mayo Clinic Jacksonville

Jacksonville, Florida, 32224

Site Contact

Vikas Majithia, MD

[email protected]

205-975-2405

Palm Beach Rheumatology and Wellness, Jupiter, Florida

Status

Recruiting

Address

Palm Beach Rheumatology and Wellness

Jupiter, Florida, 33458

Site Contact

Reshma Khan, MD

[email protected]

561-316-7033

Margate, Florida

Status

Recruiting

Address

Arthritis & Rheumatology Center of South Florida

Margate, Florida, 33063

Site Contact

Jigar Shah, MD

[email protected]

954-281-8891

Life Medical Research Group, Miami Gardens, Florida

Status

Recruiting

Address

Life Medical Research Group

Miami Gardens, Florida, 33014

Site Contact

Marisley Benitez

[email protected]

305-705-4111

Southwest Florida Rheumatology, Riverview, Florida

Status

Recruiting

Address

Southwest Florida Rheumatology

Riverview, Florida, 33569

Site Contact

Shanmugapriya Reddy, MD

[email protected]

305-300-4990

Brunswick, Georgia

Status

Recruiting

Address

Southeast Georgia Physician Associates-Rheumatology

Brunswick, Georgia, 31520

Site Contact

Erick Bournigal, MD

[email protected]

912-466-7310

Indiana University Health, Carmel, Indiana

Status

Not yet recruiting

Address

Indiana University Health

Carmel, Indiana, 46280

Site Contact

Sneha Pai

[email protected]

917-375-3112

Johns Hopkins University, Baltimore, Maryland

Status

Recruiting

Address

Johns Hopkins University

Baltimore, Maryland, 21224

Site Contact

Uzma Haque, MD

[email protected]

205-975-2405

Tufts University, Boston, Massachusetts

Status

Recruiting

Address

Tufts University

Boston, Massachusetts, 02111

Site Contact

Sreelakshmi Panginikkod, MD

[email protected]

205-975-2405

Worcester, Massachusetts

Status

Recruiting

Address

University of Massachusetts Chan Medical School

Worcester, Massachusetts, 01655

Site Contact

Jonathan Kay, MD

[email protected]

205-975-2405

Okemos, Michigan

Status

Recruiting

Address

American Arthritis and Rheumatology Associates -Mi PLLC

Okemos, Michigan, 48864

Site Contact

Srijana Bakshi, MD

[email protected]

860-679-3605

Saint Paul Rheumatology, P.A., Eagan, Minnesota

Status

Recruiting

Address

Saint Paul Rheumatology, P.A.

Eagan, Minnesota, 55121

Site Contact

David Ridley, MD

[email protected]

651-644-4277

Mayo Clinic Rochester, Rochester, Minnesota

Status

Recruiting

Address

Mayo Clinic Rochester

Rochester, Minnesota, 55905

Site Contact

Lynne Peterson, MD

[email protected]

205-975-2405

Dr. Jayashree Sinha, Clovis, New Mexico

Status

Recruiting

Address

Dr. Jayashree Sinha

Clovis, New Mexico, 88101

Site Contact

Jayashree Sinha, MD

[email protected]

575-935-5051

Inspire Santa Fe Medical Group, Santa Fe, New Mexico

Status

Recruiting

Address

Inspire Santa Fe Medical Group

Santa Fe, New Mexico, 87505

Site Contact

Arianna Lundquist

[email protected]

412-578-5676

New York University, New York, New York

Status

Recruiting

Address

New York University

New York, New York, 10016

Site Contact

Pamela Rosenthal, MD

[email protected]

205-975-2405

Hospital for Special Surgery, New York, New York

Status

Recruiting

Address

Hospital for Special Surgery

New York, New York, 10021

Site Contact

Susan Goodman, MD

[email protected]

205-975-2405

Cleveland, Ohio

Status

Recruiting

Address

University Hospital Cleveland Medical Ctr

Cleveland, Ohio, 44106

Site Contact

Marina N Magrey, MD

[email protected]

205-975-2405

The MetroHealth System, Cleveland, Ohio

Status

Recruiting

Address

The MetroHealth System

Cleveland, Ohio, 44109

Site Contact

Nora Singer, MD

[email protected]

205-975-2405

Liberty Township, Ohio

Status

Recruiting

Address

Arthritis and Rheumatology of Southwest Ohio

Liberty Township, Ohio, 45069

Site Contact

Soha Mousa, MD

[email protected]

513-779-5610

Southern Ohio Rheumatology, Wheelersburg, Ohio

Status

Recruiting

Address

Southern Ohio Rheumatology

Wheelersburg, Ohio, 45694

Site Contact

Rajesh Kataria, MD

[email protected]

740-355-8562

Oregon Health and Science University, Portland, Oregon

Status

Recruiting

Address

Oregon Health and Science University

Portland, Oregon, 97239

Site Contact

Cong-Qiu Chu, MD

[email protected]

205-975-2405

Altoona Center for Clinical Research, Duncansville, Pennsylvania

Status

Recruiting

Address

Altoona Center for Clinical Research

Duncansville, Pennsylvania, 16635

Site Contact

Alan J Kivitz, MD, CPI

[email protected]

205-975-2405

Rheumatology and Arthritis Care Center, Exton, Pennsylvania

Status

Recruiting

Address

Rheumatology and Arthritis Care Center

Exton, Pennsylvania, 19341-2547

Site Contact

Sucharitha Shanmugam, MD

[email protected]

484-206-4447

Allegheny Health Network, Pittsburgh, Pennsylvania

Status

Recruiting

Address

Allegheny Health Network

Pittsburgh, Pennsylvania, 15212

Site Contact

Paige Rutter

[email protected]

412-578-5676

Wyomissing, Pennsylvania

Status

Recruiting

Address

PA Regional Center for Arthritis and Osteoporosis Research

Wyomissing, Pennsylvania, 19610

Site Contact

Dana Cullen

[email protected]

610-374-8133

Cumberland Rhematology, Crossville, Tennessee

Status

Recruiting

Address

Cumberland Rhematology

Crossville, Tennessee, 38555

Site Contact

Sivalingam Kanagasegar, MD

[email protected]

931-459-7720

Vanderbilt University, Nashville, Tennessee

Status

Recruiting

Address

Vanderbilt University

Nashville, Tennessee, 37235

Site Contact

Kevin W Byram, MD

[email protected]

205-975-2405

Heritage Rheumatology and Arthritis Care, Colleyville, Texas

Status

Recruiting

Address

Heritage Rheumatology and Arthritis Care

Colleyville, Texas, 76034

Site Contact

Dhiman Basu, MD

[email protected]

817-590-0880

Southwest Medical Center, Dallas, Texas

Status

Recruiting

Address

Southwest Medical Center

Dallas, Texas, 75235

Site Contact

Safia Shaikh

[email protected]

469-893-1242

Texas Arthritis Center, PA, El Paso, Texas

Status

Recruiting

Address

Texas Arthritis Center, PA

El Paso, Texas, 77902

Site Contact

Sanjay Chabra, MD

[email protected]

915-317-1660

Harlingen, Texas

Status

Recruiting

Address

American Arthritis and Rheumatology Associates-Tx PLLC

Harlingen, Texas, 78550

Site Contact

Naiara Alvarez, MD

[email protected]

956-422-3122

Baylor University, Houston, Texas

Status

Not yet recruiting

Address

Baylor University

Houston, Texas, 77030

Site Contact

Kalpana Bhairavarasu

[email protected]

713-798-3390

Reston, Virginia

Status

Recruiting

Address

Northern Virginia Center for Arthritis-Reston

Reston, Virginia, 20190

Site Contact

Phong Nguyen, MD

[email protected]

703-293-5239

International Sites

Mount Sinai Hospital (Canada), Toronto, Ontario, Canada

Status

Recruiting

Address

Mount Sinai Hospital (Canada)

Toronto, Ontario, M5T 3L9

Site Contact

Bindee Kuriya, MD

[email protected]

205-975-2405