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

NCT02779114 | Unknown Phase 3 DMC

• 1 other identifier: UKER00109STUM3
• Study Type: interventional
• Target: 318
• Locations: 1 country
• Sites: 12

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.

Conditions

Rheumatoid Arthritis

Keywords

Rheumatoid Arthritis; Remission; Dose reduction

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (19)

• 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)

  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

Study Arms (3)

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.

Drug: Control group; Other: Reduction group 1; Other: Reduction group 2

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.

Drug: Control group; Other: Reduction group 1; Other: Reduction group 2

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.

Drug: Control group; Other: Reduction group 1; Other: Reduction group 2

Interventions

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®)

Control group; Reduction group 1; Reduction group 2

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®)

Control group; Reduction group 1; Reduction group 2

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.

Control group; Reduction group 1; Reduction group 2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• Treatment with Rituximab during the last 12 months before screening
• 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
• 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

Sponsors & Collaborators

• University of Erlangen-Nürnberg Medical School: lead

Study Sites (12)

Asklepios Klinikum Bad Abbach

Bad Abbach, Germany

RECRUITING

Rheumapraxis Manger

Bamberg, Germany

RECRUITING

Rheumapraxis Bayreuth

Bayreuth, Germany

RECRUITING

Schlosspark-Klinik

Berlin, Germany

RECRUITING

Schwerpunktpraxis für Rheumatologie Burghausen

Burghausen, Germany

RECRUITING

PGRN.de Praxisgemeinschaft Rheumatologie Nephrologie

Erlangen, Germany

RECRUITING

Universitätsklinikum Heidelberg; Medizinische Klinik V

Heidelberg, Germany

RECRUITING

Gemeinschaftspraxis Dres. Demary und von Hinüber

Hildesheim, Germany

RECRUITING

Praxiszentrum St. Bonifatius

München, Germany

RECRUITING

Praxis Professor Nüsslein

Nuremberg, Germany

RECRUITING

Universitätsklinikum Tübingen; Zentrum für Interdisziplinäre Klinische Immunologie, Rheumatologie und Autoimmunerkrankungen - INDIRA

Tübingen, Germany

RECRUITING

Medizinische Klinik 2 und Poliklinik, Universitätsklinikum Würzburg

Würzburg, Germany

RECRUITING

Related Publications (1)

• 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.

  PMID: 38297524 DERIVED

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

Control Groups

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Epidemiologic Research Design; Epidemiologic Methods; Investigative Techniques; Research Design; Methods

Study Officials

• Georg Schett, Prof. Dr. univ.

  University Clinic Erlangen, Clinical Trial Unit, Department of Internal Medicine 3, Rheumatology & Immunology

  STUDY DIRECTOR

Central Study Contacts

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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 16, 2016
• First Posted: May 20, 2016
• Study Start: January 1, 2009
• Primary Completion: December 1, 2017
• Study Completion: June 1, 2018
• Last Updated: May 23, 2016

Record last verified: 2016-05

Data Sharing

• IPD Sharing: Will share

Locations

DE (12)