This site became the new ClinicalTrials.gov on June 19th. Learn more.
Show more
ClinicalTrials.gov Menu IMPORTANT: Listing of a study on this site does not reflect endorsement by the National Institutes of Health. Talk with a trusted healthcare professional before volunteering for a study. Read more...
ClinicalTrials.gov Menu IMPORTANT: Talk with a trusted healthcare professional before volunteering for a study. Read more...
ClinicalTrials.gov Menu
Give us feedback
Trial record 1 of 1 for:    13-AR-0056
Previous Study | Return to List | Next Study

Stopping TNF Alpha Inhibitors in Rheumatoid Arthritis (STARA)

This study is currently recruiting participants.
See Contacts and Locations
Verified August 2016 by Georgetown University
Sponsor:
Collaborators:
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
University of Maryland
Washington D.C. Veterans Affairs Medical Center
Washington Hospital Center
Patient-Centered Outcomes Research Institute
Arthritis and Pain Associates of PG County
Arthritis & Rheumatism Associates, P.C.
Rheumatology Associates of Baltimore, L.L.C.
The Arthritis Clinic of Northern Virginia, P.C.
Arthritis and Rheumatic Disease Associates, P.C.
Information provided by (Responsible Party):
Georgetown University
ClinicalTrials.gov Identifier:
NCT01793519
First received: February 14, 2013
Last updated: November 4, 2016
Last verified: August 2016
February 14, 2013
November 4, 2016
January 2013
December 2018   (Final data collection date for primary outcome measure)
Remission by Disease Activity Score - 28 over 48 weeks [ Time Frame: 48 weeks ]
Same as current
Complete list of historical versions of study NCT01793519 on ClinicalTrials.gov Archive Site
  • Change in Health Assessment Questionnaire Disability Index over 48 weeks [ Time Frame: 48 weeks ]
  • Change in Sharp-van der Heijde radiographic score over 48 weeks [ Time Frame: 48 weeks ]
Same as current
Not Provided
Not Provided
 
Stopping TNF Alpha Inhibitors in Rheumatoid Arthritis
Stopping Tumor Necrosis Factor-Alpha Inhibitors in Rheumatoid Arthritis (STARA) Clinical Trial

Background:

  • Rheumatoid arthritis (RA) is often treated with drugs known as tumor necrosis factor (TNF) inhibitors, that can help decrease joint pain and swelling and can even result in RA remission. However, TNF inhibitors may increase risk of serious infections or some types of cancer.
  • It is not clear if people whose RA has been in remission for a long time need to stay on the TNF inhibitor to remain in remission. If they can stop taking the TNF inhibitor without having their symptoms come back, they will be spared the side effects of these medicines. Some studies have shown that people can stay in remission after stopping a TNF inhibitor, but other studies have not confirmed it. Researchers want to see if people with RA in remission on a TNF inhibitor can stay in remission without this medicine. Also there may be a clinical, imaging (MRI, ultrasound), laboratory profile that will help to determine which patients remain in remission after stopping these drugs.

Objectives:

  • To see whether RA remission can continue after discontinuing use of a TNF inhibitor.
  • To determine if clinical, imaging and immunological measurements can predict which participants will flare and which will remain in remission after discontinuing TNF inhibitor.

Eligibility:

-Individuals at least 18 years of age who have RA that is being controlled with TNF inhibitors. We plan to randomize 291 patients.

Design:

  • The study has seven visits over about 2 years. Six visits occur in the first year of the study, about 12 weeks apart. The final study visit is 1 year after the end of the treatment phase.
  • At the first visit, participants will be screened with a physical exam and medical history. They will complete a questionnaire about their RA symptoms. A blood sample will be collected. They will continue to take their RA medicines during this time.
  • The second visit will repeat tests from the first visit. These tests will confirm that the RA is in remission. Imaging studies will be performed on the hands, wrists, feet, and their connected joints. After this visit, participants will stop taking their TNF inhibitors and will start to have injections of a study drug. This drug will be either the participant's original TNF inhibitor or a placebo.
  • There will be follow-up visits at weeks 12, 24, and 36. Participants will have a medical history and joint exam. They will also provide blood samples and answer questions about their RA symptoms.
  • At the sixth visit (week 48), participants will repeat the tests and imaging studies from the second visit. They will stop taking the study injections.
  • Continued RA treatment after this visit will be decided by the participant and his or her rheumatologist. Participants may take any recommended medicine, including the TNF inhibitor they had been taking before the study. They will also receive a questionnaire to complete at home and mail back before the final study visit.
  • At the final visit (week 100), participants will repeat the tests and imaging studies from the second and sixth visits.

Remission of rheumatoid arthritis (RA) is an achievable goal with currently available medications, including the anti-tumor necrosis factor (anti-TNF) agents. However, it is uncertain if patients with RA in clinical remission while treated with anti-TNF agents and background disease-modifying antirheumatic drugs (DMARD) would remain in remission if anti-TNF therapy was stopped. If remission can be sustained off anti-TNF agents, then patients may be spared the potential toxicity and costs of these medications.

The Stopping Anti-Tumor Necrosis Factor Agents in Rheumatoid Arthritis (STARA) study is a multicenter, randomized, double-blind, placebo-controlled noninferiority trial that will test differences in time to relapse between patients with RA in remission who discontinue anti-TNF agents and patients with RA in remission who continue anti-TNF agents. The secondary objectives of the study are: 1) to determine if discontinuation of anti-TNF agents results in a difference in progression of joint damage on radiographs; 2) to determine if discontinuation of anti-TNF agents results in a difference in physical function, and 3) to identify predictors of relapse.

Eligible subjects will have RA in remission for at least six months while taking etanercept, infliximab, or adalimumab. An eight-week run-in period prior to randomization will be used to confirm remission. Subjects will then be randomized in a 2:1 ratio to receive one of two blinded treatments: 1) matching placebo or 2) their currently used anti-TNF agent, respectively. All subjects will maintain their current background DMARD. Clinical assessments will be performed every 12 weeks. The primary outcome is 48-week relapse-free status. Secondary outcomes include change from baseline radiographic joint damage score at 48 weeks and 100 weeks, and change from baseline physical function score at 48 weeks. Subjects who relapse before week 48 will discontinue study medication and receive treatment through their rheumatologist. Blinded treated will end at week 48 and subjects will be followed for 52 additional weeks. This study will provide important new information on the best treatment approach for patients with RA in remission.

Interventional
Phase 4
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Rheumatoid Arthritis
  • Drug: Etanercept
    Subcutaneous
    Other Name: Enbrel
  • Drug: Infliximab
    Infusion
    Other Name: Remicade
  • Drug: Adalimumab
    Subcutaneous
    Other Name: Humira
  • Drug: Placebo
    Matching Placebo
  • Active Comparator: Anti-tumor necrosis factor agent
    Anti-TNF agent - etanercept, infliximab, adalimumab - administered parentally at standard dosage and frequencies
    Interventions:
    • Drug: Etanercept
    • Drug: Infliximab
    • Drug: Adalimumab
  • Placebo Comparator: Placebo
    Administered appropriately to active comparator
    Intervention: Drug: Placebo

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
290
December 2018
December 2018   (Final data collection date for primary outcome measure)
  • Study personnel will evaluate participant eligibility using a checklist of inclusion and exclusion criteria as outlined below. Clinical information will be obtained from subjects by interview and from the medical record.

At the screening visit, potential participants will be included if:

  • Age greater than or equal to 18 years
  • Have RA, as defined by the 1987 revised American College of Rheumatology criteria
  • In sustained clinical remission for the last 6 months while receiving treatment with either etanercept, infliximab, or adalimumab, and greater than or equal to 1 DMARD (methotrexate, hydroxychloroquine, sulfasalazine, leflunomide, minocycline, cyclosporine, azathioprine, gold, penicillamine). DAS28 should be less than 2.6 on each visit over the preceding 6 months, with at least one visit 2-4 months before enrollment. If there is no visit 6 months before enrollment, the nearest visit in the 6-12 month period before enrollment should be considered and have a DAS28 less than 2.6.

Potential participants will be excluded if:

  • Had dose increase of anti-TNF agent or DMARD in the last 6 months
  • Had change of anti-TNF agent or DMARD in the last 6 months
  • Treated currently with golimumab or certolizumab
  • Treated with greater than 10 mg of prednisone (or equivalent) daily in the last 6 months
  • Treated with greater than 5 mg of prednisone (or equivalent) daily in the last 3 months
  • Treated with intramuscular or intravenous corticosteroids in the last 6 months for RA activity
  • Treated with anakinra, abatacept, or tocilizumab in the last 6 months
  • Treated with rituximab in the last 12 months
  • Treated with an investigational RA drug in the last 6 months
  • Pregnant (or anticipate pregnancy during the study period) or lactating women
  • Absence of documentation in the medical record of clinical remission for the last 6 months
  • Unwilling to discontinue anti-TNF agent
  • Absence of documentation of negative tuberculin skin test, negative QuantiFERON-TB Gold test, or treatment for latent tuberculosis prior to starting treatment with the anti-TNF agent
  • Treatment of solid malignancy or non-melanoma skin cancer within the past 5 years, or any history of melanoma or hematologic or lymphoproliferative malignancy
  • Absence of documentation of age-appropriate cancer screening at the time of randomization
  • Absence of documentation of negative hepatitis B serologies, absence of completion of treatment for chronic hepatitis B, or absence of suppressive antiviral treatment
  • Unable to provide informed consent
  • Anticipate not being available or able to comply with the schedule of study visits

Study entry is not limited by gender or ethnicity. Children are excluded because inflammatory polyarthritis developing before age 16 is considered juvenile idiopathic arthritis and not RA. Patients who developed RA while age 17 would be eligible, but given the time needed to achieve remission, these patients would in most cases be 18 or older by the time they would meet other criteria for study entry.

Participants will largely be recruited from the practices of study investigators. To identify potential subjects, investigators may search rosters of patients in their practice for patients who meet the inclusion criteria. The number of patients screened and reasons for exclusion will be tabulated at each site. Subjects may also be recruited by physician referral. Information about the study will be mailed to local rheumatologists and posted on the NIAMS website. We do not anticipate self-referral of subjects but eligible self-referred subjects will not be excluded.

During the course of the study, enrollment of subjects treated with a particular anti-TNF agent may be suspended or terminated to permit adequate representation of patients treated with each of the 3 anti-TNF medications, due to problems procuring medication, or due to other unforeseen issues.

Sexes Eligible for Study: All
18 Years and older   (Adult, Senior)
No
Contact: Arthur Weinstein, M.D. (202) 877-6274 aw89@georgetown.edu
Contact: Michael M Ward, M.D. (301) 496-7263 wardm1@mail.nih.gov
United States
 
 
NCT01793519
CER-1402-10522
13-AR-0056 ( Other Identifier: Internal NIAMS assigned number )
CER-1402-10522 ( Other Grant/Funding Number: PCORI )
Yes
Not Provided
Plan to Share IPD: Undecided
Georgetown University
Georgetown University
  • National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
  • University of Maryland
  • Washington D.C. Veterans Affairs Medical Center
  • Washington Hospital Center
  • Patient-Centered Outcomes Research Institute
  • Arthritis and Pain Associates of PG County
  • Arthritis & Rheumatism Associates, P.C.
  • Rheumatology Associates of Baltimore, L.L.C.
  • The Arthritis Clinic of Northern Virginia, P.C.
  • Arthritis and Rheumatic Disease Associates, P.C.
Principal Investigator: Michael M Ward, M.D. National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Principal Investigator: Arthur Weinstein, MD Georgetown University
Georgetown University
August 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP