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This is a phase 3, multicenter, randomized, open, prospective, controlled, parallel-group intervention study in 318 patients with Rheumatoid Arthritis. The study is composed of 3 phases: a pre-randomization phase for up to 10 days followed by a 1-year randomized, open three arm treatment phase for each patient, followed by a 5-year observational phase for all patients still in remission.
Rheumatoid Arthritis (RA) is characterized by progressive synovitis leading to degradation of articular cartilage leading to erosions in juxtaarticular bones driven by auto antibodies. Few clinical studies could show that quick and thorough control of inflammatory processes could stop degradation processes [17, 18, 19, 20, 21] and had presumably better prognosis of remission than untreated and/or uncontrolled RA disease [20]. These studies aimed at low disease activity [20], often focused on early RA [18, 19], evaluating different therapy strategies, mostly escalating instead of deescalating medications [20, 21]. Real "RA- in - remission" or therapy reduction studies are missing up to now, even if first small trials focusing on one preparation showed promising results [16, 17].
In this study all conventional medications in usual combinations are being evaluated for the treatment of Rheumatoid Arthritis in different stages of disease duration. The study is scheduled as a 365-day (12-months), phase 3 multicenter, randomized, open, prospective, controlled, parallel-group intervention study in 318 patients with Rheumatoid Arthritis.
Based on the results of the clinical studies mentioned above, and the need for a guideline with therapy proposals for RA- patients in remission all current preparations will be evaluated in subjects under the controlled setting of a clinical study. The information obtained from this study will assess the formulation of new guidelines regarding patients with Rheumatoid Arthritis in remission.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Control group | Other | After 1:1:1 randomization patients in the control group receive their previous disease modifying therapy of conventional DMARD, biologicals and glucocorticoids during 12 months of the study. |
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| Reduction group 1 | Other | Patients in reduction group 1 receive exactly 50% of their previous disease modifying therapy of conventional DMARD, biologicals and glucocorticoids during the first six months of the study. |
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| Reduction group 2 | Other | Patients in reduction group 2 receive exactly 50% of their previous disease modifying therapy of conventional DMARD, biologicals and glucocorticoids during the first six months of the study. If they are still in remission they will discontinue their previous disease modifying therapy of conventional DMARD, biologicals and glucocorticoids during the first six months of the study. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Control group | Drug | Stable dosage of previous treatment with Decortin H®, Leflunomid (e.g. Arava®), Ciclosporin (e.g. Immunosporin®), Sulfasalazin (e.g. Azulfidine RA®, Pleon RA®), Hydroxychloroquine (e.g. Quensyl®); Azathioprin, Methotrexate (e.g. Lantarel®, Metex®), Etanercept (Enbrel®), Adalimumab (Humira®), Infliximab (Remicade®), Tocilizumab (RoActemra®), Golimumab (Simponi®), Certolizumab (Cimzia®), Abatacept (Orencia®) |
| Measure | Description | Time Frame |
|---|---|---|
| Proportion of subjects in each treatment group who are still in remission after 12 months (remission defined as DAS 28 < 2.6) reduction or even discontinuation in RA-patients after achievement of long lasting remission. | 12 months |
| Measure | Description | Time Frame |
|---|---|---|
| Proportion of subjects in each treatment group who are still in remission after 3, 6, 9 months (remission defined as DAS 28 < 2.6). | 12 months | |
| Proportion of subjects in each treatment group who are still in remission after 3, 6, 9 months (remission defined according to Pinals - criteria) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Georg Schett, Prof. Dr. univ. | Contact | +49-9131-8533418 | georg.schett@uk-erlangen.de | |
| Juergen Rech, Dr. med. | Contact | +49-9131-8543014 | juergen.rech@uk-erlangen.de |
| Name | Affiliation | Role |
|---|---|---|
| Georg Schett, Prof. Dr. univ. | University Clinic Erlangen, Clinical Trial Unit, Department of Internal Medicine 3, Rheumatology & Immunology | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Asklepios Klinikum Bad Abbach | Recruiting | Bad Abbach | Germany |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 38297524 | Derived | Tascilar K, Hagen M, Kleyer A, Simon D, Reiser M, Hueber AJ, Manger B, Englbrecht M, Finzel S, Tony HP, Schuch F, Kleinert S, Wendler J, Ronneberger M, Figueiredo CP, Cobra JF, Feuchtenberger M, Fleck M, Manger K, Ochs W, Schmitt-Haendle M, Lorenz HM, Nuesslein H, Alten R, Kruger K, Henes J, Schett G, Rech J. Treatment tapering and stopping in patients with rheumatoid arthritis in stable remission (RETRO): a multicentre, randomised, controlled, open-label, phase 3 trial. Lancet Rheumatol. 2021 Nov;3(11):e767-e777. doi: 10.1016/S2665-9913(21)00220-4. Epub 2021 Oct 1. |
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| ID | Term |
|---|---|
| D001172 | Arthritis, Rheumatoid |
| ID | Term |
|---|---|
| D001168 | Arthritis |
| D007592 | Joint Diseases |
| D009140 | Musculoskeletal Diseases |
| D012216 | Rheumatic Diseases |
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| ID | Term |
|---|---|
| D035061 | Control Groups |
| ID | Term |
|---|---|
| D015340 | Epidemiologic Research Design |
| D004812 | Epidemiologic Methods |
| D008919 | Investigative Techniques |
| D012107 | Research Design |
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|
| Reduction group 1 | Other | Dose reduction of 50% for 12 months of previous treatment with Decortin H®, Leflunomid (e.g. Arava®), Ciclosporin (e.g. Immunosporin®), Sulfasalazin (e.g. Azulfidine RA®, Pleon RA®), Hydroxychloroquine (e.g. Quensyl®); Azathioprin, Methotrexate (e.g. Lantarel®, Metex®), Etanercept (Enbrel®), Adalimumab (Humira®), Infliximab (Remicade®), Tocilizumab (RoActemra®), Golimumab (Simponi®), Certolizumab (Cimzia®), Abatacept (Orencia®) |
|
| Reduction group 2 | Other | Dose reduction of 50% of previous treatment with Decortin H®, Leflunomid (e.g. Arava®), Ciclosporin (e.g. Immunosporin®), Sulfasalazin (e.g. Azulfidine RA®, Pleon RA®), Hydroxychloroquine (e.g. Quensyl®); Azathioprin, Methotrexate (e.g. Lantarel®, Metex®), Etanercept (Enbrel®), Adalimumab (Humira®), Infliximab (Remicade®), Tocilizumab (RoActemra®), Golimumab (Simponi®), Certolizumab (Cimzia®), Abatacept (Orencia®) for 6 months and if they are still in remission therapy will be discontinued. |
|
| 12months |
| Proportion of subjects in each treatment group with increased disease activity | 12 months |
| Proportion of adverse events (to be documented via "unscheduled visit"-sheet) | 12 months |
| DAS 28 after 3, 6, 9 and 12 months | 12 months |
| CRP after 3, 6, 9 and 12 months | 12 months |
| ESR after 3, 6, 9 and 12 months | 12 months |
| Swollen joint counts after 3, 6, 9 and 12 months | 12 months |
| Tender joint counts after 3, 6, 9 and 12 months | 12 months |
| Patient self assessment of pain (VAS) after 3, 6, 9 and 12 months | 12 months |
| Physician's and patient's assessment of global disease activity (VAS) after 3, 6, 9 and 12 months | 12 months |
| Duration of joint stiffness after 3, 6, 9 and 12 months | 12 months |
| HAQ (Health Assessment Questionnaire) after 3, 6, 9 and 12 months | 12 months |
| SF-36 (Short Form) Score after 3, 6, 9 and 12 months | 12 months |
| Coping-Questionnaire after 3, 6, 9 and 12 months | 12 months |
| PASS (patient acceptable symptom state) after 3, 6, 9 and 12 months | 12 months |
| WPAI:RA (Work Productivity and Activity Impairment Questionnaire) after 3, 6, 9, 12 months | 12 months |
| BDI - II (Beck-Depression Inventory) after 3, 6, 9 and 12 months | 12 months |
| Flare Questionnaire RA (German version): At time of potential flare | 12 months |
| Rheumapraxis Manger | Recruiting | Bamberg | Germany |
|
| Rheumapraxis Bayreuth | Recruiting | Bayreuth | Germany |
|
| Schlosspark-Klinik | Recruiting | Berlin | Germany |
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| Schwerpunktpraxis für Rheumatologie Burghausen | Recruiting | Burghausen | Germany |
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| PGRN.de Praxisgemeinschaft Rheumatologie Nephrologie | Recruiting | Erlangen | Germany |
|
| Universitätsklinikum Heidelberg; Medizinische Klinik V | Recruiting | Heidelberg | Germany |
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| Gemeinschaftspraxis Dres. Demary und von Hinüber | Recruiting | Hildesheim | Germany |
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| Praxiszentrum St. Bonifatius | Recruiting | München | Germany |
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| Praxis Professor Nüsslein | Recruiting | Nuremberg | Germany |
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| Universitätsklinikum Tübingen; Zentrum für Interdisziplinäre Klinische Immunologie, Rheumatologie und Autoimmunerkrankungen - INDIRA | Recruiting | Tübingen | Germany |
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| Medizinische Klinik 2 und Poliklinik, Universitätsklinikum Würzburg | Recruiting | Würzburg | Germany |
|
| D003240 |
| Connective Tissue Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
| D008722 | Methods |