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RETRO (REduction of Therapy in RA Patients in Ongoing Remission) (RETRO)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02779114
Recruitment Status : Unknown
Verified May 2016 by University of Erlangen-Nürnberg Medical School.
Recruitment status was:  Recruiting
First Posted : May 20, 2016
Last Update Posted : May 23, 2016
Sponsor:
Information provided by (Responsible Party):
University of Erlangen-Nürnberg Medical School

Tracking Information
First Submitted Date  ICMJE May 16, 2016
First Posted Date  ICMJE May 20, 2016
Last Update Posted Date May 23, 2016
Study Start Date  ICMJE January 2009
Estimated Primary Completion Date December 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 17, 2016)
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. [ Time Frame: 12 months ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 17, 2016)
  • Proportion of subjects in each treatment group who are still in remission after 3, 6, 9 months (remission defined as DAS 28 < 2.6). [ Time Frame: 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) [ Time Frame: 12months ]
  • Proportion of subjects in each treatment group with increased disease activity [ Time Frame: 12 months ]
  • Proportion of adverse events (to be documented via "unscheduled visit"-sheet) [ Time Frame: 12 months ]
  • DAS 28 after 3, 6, 9 and 12 months [ Time Frame: 12 months ]
  • CRP after 3, 6, 9 and 12 months [ Time Frame: 12 months ]
  • ESR after 3, 6, 9 and 12 months [ Time Frame: 12 months ]
  • Swollen joint counts after 3, 6, 9 and 12 months [ Time Frame: 12 months ]
  • Tender joint counts after 3, 6, 9 and 12 months [ Time Frame: 12 months ]
  • Patient self assessment of pain (VAS) after 3, 6, 9 and 12 months [ Time Frame: 12 months ]
  • Physician's and patient's assessment of global disease activity (VAS) after 3, 6, 9 and 12 months [ Time Frame: 12 months ]
  • Duration of joint stiffness after 3, 6, 9 and 12 months [ Time Frame: 12 months ]
  • HAQ (Health Assessment Questionnaire) after 3, 6, 9 and 12 months [ Time Frame: 12 months ]
  • SF-36 (Short Form) Score after 3, 6, 9 and 12 months [ Time Frame: 12 months ]
  • Coping-Questionnaire after 3, 6, 9 and 12 months [ Time Frame: 12 months ]
  • PASS (patient acceptable symptom state) after 3, 6, 9 and 12 months [ Time Frame: 12 months ]
  • WPAI:RA (Work Productivity and Activity Impairment Questionnaire) after 3, 6, 9, 12 months [ Time Frame: 12 months ]
  • BDI - II (Beck-Depression Inventory) after 3, 6, 9 and 12 months [ Time Frame: 12 months ]
  • Flare Questionnaire RA (German version): At time of potential flare [ Time Frame: 12 months ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE RETRO (REduction of Therapy in RA Patients in Ongoing Remission)
Official Title  ICMJE A Phase 3, Multicenter, Randomized, Open, Prospective, Controlled, Parallel Group Study of Reduction of Therapy in Patients With Rheumatoid Arthritis in Ongoing Remission.
Brief Summary 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.
Detailed Description

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Rheumatoid Arthritis
Intervention  ICMJE
  • Drug: Control group
    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®)
  • Other: Reduction group 1
    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®)
  • Other: Reduction group 2
    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.
Study Arms  ICMJE
  • Control group
    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.
    Interventions:
    • Drug: Control group
    • Other: Reduction group 1
    • Other: Reduction group 2
  • Reduction group 1
    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.
    Interventions:
    • Drug: Control group
    • Other: Reduction group 1
    • Other: Reduction group 2
  • Reduction group 2
    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.
    Interventions:
    • Drug: Control group
    • Other: Reduction group 1
    • Other: Reduction group 2
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Unknown status
Estimated Enrollment  ICMJE
 (submitted: May 17, 2016)
318
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 2018
Estimated Primary Completion Date December 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Must understand and voluntarily sign an informed consent form including written consentfor data protection
  • Must be able to adhere to the study visit schedule and other protocol requirements
  • Must be male or female and aged ≥ 18 years at time of consent
  • Must have a diagnosis of RA according to ACR criteria [26] for at least 12 months
  • Must have a DAS 28 score of less than 2.6 (means: remission) at randomization (documented in at least three subsequent controls for six months; compare figure three in the appendix for details)
  • At screening-visit patients should have been treated without alterations of therapy for at least six months with one of the following therapies: (i) one or more of the following conventional DMARDS (with or without concomitant use of glucocorticoids): Methotrexate, Leflunomide, Ciclosporine A, Sulfasalazine, Azathioprine or Hydroxychloroquine, (ii) a combination of a conventional DMARD (Methotrexate, Leflunomide, Ciclosporine A, Sulfasalazine, Azathioprine or Hydroxychloroquine) with one of the following biologicals (with or without concomitant use of glucocorticoids): Infliximab, Adalimumab, Etanercept, Tocilizumab, Golimumab, Certolizumab, Abatacept, (iii) or one of the biologicals mentioned above without combination with a conventional DMARD. All of the aforementioned biologicals are also allowed in combination with glucocorticoids, (iv) monotherapy treatment with glucocorticoids (without any DMARD or biological treatment).

Exclusion Criteria:

  • Treatment with Rituximab during the last 12 months before screening
  • Intake of a daily dosage of more than 5mg Prednisolone - equivalent during the last 6 months before randomization; intraarticular injections of glucocorticoids do not represent an exclusion criteria
  • Current treatment with other DMARDS (for example MMF or preparations still in development) than mentioned above
  • Any anti-inflammatory or immunosuppressive therapy for other reasons than RA during the last 3 months before screening
  • Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study
  • Any other rheumatological/immunological disease such as Psoriasis, Psoriatic Arthritis, SLE, PSS, MCTD, M. Bechterew, M. Behcet or M. Wegener. Should the respective diagnosis be confirmed after inclusion into the study the patient will leave the study and data is recorded via "unscheduled visit"- and follow-up form
  • Florid autoimmune conditions such as autoimmune hepatitis or Hashimoto's disease while still under treatment
  • Patients with a florid malignancy
  • Participation in another phase 1-4 treatment study for RA
  • Patients who are younger than 18 years or are incapable to understand the aim, importance and consequences of the study and to give legal informed consent (according to § 40 Abs. 4 and § 41 Abs. 2 und Abs. 3 AMG)
  • Pregnant or lactating female
  • Females of childbearing potential (FCBP is a sexually mature female who 1. has not undergone a hysterectomy or bilateral oophorectomy, or 2. has not been postmenopausal for at least 24 consecutive months) have to use adequate forms of contraception with respect to standard treatment recommendations. However if there is suspicion of a pregnancy in spite of standard treatment recommendations a urine pregnancy test is to be carried out by the Investigator
  • Also males must also use adequate forms of contraception
  • Patients who possibly are dependent on the Principal Investigator or investigator
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Germany
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02779114
Other Study ID Numbers  ICMJE UKER00109STUM3
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Responsible Party University of Erlangen-Nürnberg Medical School
Study Sponsor  ICMJE University of Erlangen-Nürnberg Medical School
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Georg Schett, Prof. Dr. univ. University Clinic Erlangen, Clinical Trial Unit, Department of Internal Medicine 3, Rheumatology & Immunology
PRS Account University of Erlangen-Nürnberg Medical School
Verification Date May 2016

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