Trial record 1 of 1 for:    13-AR-0056
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Stopping TNF Alpha Inhibitors in Rheumatoid Arthritis

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2013 by National Institutes of Health Clinical Center (CC)
Sponsor:
Collaborators:
Medstar Research Institute
Georgetown University
Washington D.C. Veterans Affairs Medical Center
Medstar Washington Hospital Center
American College of Rheumatology Research Foundation, Atlanta, Georgia
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) )
ClinicalTrials.gov Identifier:
NCT01793519
First received: February 14, 2013
Last updated: September 12, 2014
Last verified: November 2013
  Purpose

Background:

  • Rheumatoid arthritis (RA) can be treated with different drugs. The drugs, known as tumor necrosis factor (TNF) inhibitors, can help decrease joint pain and swelling. TNF inhibitors can help RA go into remission, with no (or very few) symptoms of RA and no joint swelling or tenderness. 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.

Objectives:

- To see whether RA remission can continue after discontinuing use of a TNF inhibitor.

Eligibility:

- Individuals at least 18 years of age who have RA that is being controlled with TNF inhibitors.

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.

Condition Intervention Phase
Rheumatoid Arthritis
Drug: Etanercept
Drug: Infliximab
Drug: Adalimumab
Drug: Placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Stopping Tumor Necrosis Factor-Alpha Inhibitors in Rheumatoid Arthritis

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • Remission by Disease Activity Score - 28 over 48 weeks [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change in Health Assessment Questionnaire Disability Index over 48 weeks [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
  • Change in Sharp-van der Heijde radiographic score over 48 weeks [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 400
Study Start Date: January 2013
Estimated Study Completion Date: December 2018
Estimated Primary Completion Date: December 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Anti-tumor necrosis factor agent
Etanercept, infliximab, or adalimumab
Drug: Etanercept
N/A
Drug: Infliximab
N/A
Drug: Adalimumab
N/A
Placebo Comparator: Placebo Drug: Placebo
Matching Placebo

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
  • 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, hepatitis C serologies, or absence of completion of treatment for chronic hepatitis B
  • 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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01793519

Contacts
Contact: Arthur Weinstein, M.D. (301) 560-7301 arthur.weinstein@medstar.net
Contact: Michael M Ward, M.D. (301) 496-7263 wardm1@mail.nih.gov

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact Patient Recruitment and Public Liaison Office (PRPL)    800-411-1222 ext TTY8664111010    prpl@mail.cc.nih.gov   
Sponsors and Collaborators
Medstar Research Institute
Georgetown University
Washington D.C. Veterans Affairs Medical Center
Medstar Washington Hospital Center
American College of Rheumatology Research Foundation, Atlanta, Georgia
Investigators
Principal Investigator: Michael M Ward, M.D. National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
  More Information

Additional Information:
Publications:
Responsible Party: National Institutes of Health Clinical Center (CC) ( National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) )
ClinicalTrials.gov Identifier: NCT01793519     History of Changes
Other Study ID Numbers: 130056, 13-AR-0056
Study First Received: February 14, 2013
Last Updated: September 12, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Rheumatoid Arthritis
Autoimmune Diseases
Anti-TNF

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Adalimumab
Infliximab
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Antirheumatic Agents
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Dermatologic Agents
Gastrointestinal Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on September 16, 2014