Stopping TNF Alpha Inhibitors in Rheumatoid Arthritis (STARA)
- 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.
- 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.
-Individuals at least 18 years of age who have RA that is being controlled with TNF inhibitors. We plan to randomize 291 patients.
- 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.
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||Stopping Tumor Necrosis Factor-Alpha Inhibitors in Rheumatoid Arthritis (STARA) Clinical Trial|
- Remission by Disease Activity Score - 28 over 48 weeks [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
- 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 ]
|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)|
Active Comparator: Anti-tumor necrosis factor agent
Anti-TNF agent - etanercept, infliximab, adalimumab - administered parentally at standard dosage and frequencies
Other Name: EnbrelDrug: Infliximab
Other Name: RemicadeDrug: Adalimumab
Other Name: Humira
Placebo Comparator: Placebo
Administered appropriately to active comparator
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01793519
|Contact: Arthur Weinstein, M.D.||(202) email@example.com|
|Contact: Michael M Ward, M.D.||(301) firstname.lastname@example.org|
|United States, District of Columbia|
|Georgetown University Medical Center||Recruiting|
|Washington, District of Columbia, United States, 20007|
|Contact: Monica Siegel 336-392-0586 email@example.com|
|Contact: Arthur Weinstein, MD 3015807522 firstname.lastname@example.org|
|Principal Investigator: Arthur Weinstein, MD|
|United States, Maryland|
|National Institutes of Health Clinical Center||Recruiting|
|Bethesda, Maryland, United States, 20892|
|Contact: Patient Recruitment and Public Liaison Office (PRPL) 800-411-1222 ext TTY8664111010 email@example.com|
|Principal Investigator: Michael M Ward, MD|
|Principal Investigator:||Michael M Ward, M.D.||National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)|
|Principal Investigator:||Arthur Weinstein, MD||Georgetown University|