A PHASE 3, MULTICENTER, RANDOMIZED, OPEN, PROSPECTIVE, CONTROLLED, PARALLEL-GROUP STUDY OF REDUCTION OF THERAPY IN PATIENTS WITH RHEUMATOID ARTHRITIS IN ONGOING REMISSION RETRO – REduction of Therapy in RA patients in Ongoing remission, Reduzierung der Therapie bei RA-Patienten in Remission - RETRO

• Register: EUCTR
• Last refreshed on: 10 August 2021
• Main ID: EUCTR2009-015740-42-DE
• Date of registration: 12/01/2010
• Prospective Registration: Yes
• Primary sponsor: Universitätsklinkum Erlangen
• Public title: A PHASE 3, MULTICENTER, RANDOMIZED, OPEN, PROSPECTIVE, CONTROLLED, PARALLEL-GROUP STUDY OF REDUCTION OF THERAPY IN PATIENTS WITH RHEUMATOID ARTHRITIS IN ONGOING REMISSION RETRO – REduction of Therapy in RA patients in Ongoing remission, Reduzierung der Therapie bei RA-Patienten in Remission - RETRO
• Scientific title: A PHASE 3, MULTICENTER, RANDOMIZED, OPEN, PROSPECTIVE, CONTROLLED, PARALLEL-GROUP STUDY OF REDUCTION OF THERAPY IN PATIENTS WITH RHEUMATOID ARTHRITIS IN ONGOING REMISSION RETRO – REduction of Therapy in RA patients in Ongoing remission, Reduzierung der Therapie bei RA-Patienten in Remission - RETRO
• Date of first enrolment: 12/05/2010
• Target sample size: 318
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2009-015740-42
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: yes; Single blind: no; Double blind: no; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: yes; Other specify the comparator: control group
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Germany

Key inclusion & exclusion criteria

Inclusion criteria:
• Must understand and voluntarily sign an informed consent form
• 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 for at least 12 months
• Must have a DAS 28 score of less than 2,6 (means: remission) at randomization (documented continuously in two subsequent controls for six months)
• 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: 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: Infliximab, Adalimumab, Etanercept, Tocilizumab, Golimumab, Certolizumab, (iii) or one of the biologicals mentioned above without combination with a conventional DMARD: Infliximab, Adalimumab, Etanercept, Tocilizumab, Golimumab, Certolizumab; all of them possibly combined with steroids.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
• Treatment with Rituximab and/or Abatacept 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 cortisone injections 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
• Non-compliance
• Any other rheumatological disease such as Psoriasis, 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 „unsceduled visit“ – and follow-up form.
• Floride autoimmune conditions such as autoimmune hepatitis or Hashimoto’s disease while still under treatment
• Participation in another phase 1-4 treatment study for RA
• 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) must have a negative urine pregnancy test at screening (Visit 1). In addition, sexually active FCBP must agree to use TWO of the following adequate forms of contraception during the first 12 months of the study: oral, injectable, or implantable hormonal contraceptives; tubal ligation; intrauterine device; barrier contraceptive with spermicide; or vasectomized partner. An occurred pregnancy is to be immediately reported to the investigating rheumatologist. The clinician will record the pregnancy via an SAE-form and start a therapy appropriate in cases of pregnancy. Patient who become pregnant during the course of the first 12 months of study leave the study yet data are reported continuously via the “Pregnancy”-form.
• Males must report an occurred pregnancy of their partner immediately to the investigating clinician; this event does not represent an exclusion criteria




Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Rheumatoid arthritis
MedDRA version: 17.1 Level: PT Classification code 10039073 Term: Rheumatoid arthritis System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders

Intervention(s)

Product Name: Prednisolon
Product Code: Prednisolon
Pharmaceutical Form: Tablet
INN or Proposed INN: PREDNISOLONE
CAS Number: 50-24-8

Trade Name: Humira
Pharmaceutical Form: Injection
INN or Proposed INN: ADALIMUMAB
CAS Number: 331731-18-1

Product Name: Azathioprin
Pharmaceutical Form: Coated tablet
CAS Number: 446-86-6
Current Sponsor code: 52424.00.00
Other descriptive name: AZATHIOPRINE
Concentration unit: mg/kg milligram(s)/kilogram

Trade Name: Immunosporin
Product Name: Immunosporin
Pharmaceutical Form: Tablet
INN or Proposed INN: CICLOSPORIN
CAS Number: 59865-13-3

Trade Name: Cimzia
Product Name: Cimzia
Pharmaceutical Form: Injection
INN or Proposed INN: GOLIMUMAB
CAS Number: 476181-74-5
Current Sponsor code: EU/1/09/544/001-002
Concentration unit: mg milligram(s)

Trade Name: Enbrel
Product Name: Enbrel
Pharmaceutical Form: Injection
INN or Proposed INN: ETANERCEPT
CAS Number: 185243690
Current Sponsor code: EU/1/99/126/016
Concentration unit: mg milligram(s)

Product Name: Quensyl
Pharmaceutical Form: Tablet
CAS Number: 747-36-4
Other descriptive name: HYDROXYCHLOROQUINE SULFATE
Concentration unit: mg/kg milligram(s)/kilogram

Trade Name: REMICADE
Product Name: Remicade
Pharmaceutical Form:
INN or Proposed INN: INFLIXIMAB
CAS Number: 170277-31-3
Current Sponsor code: EU/1/99/116/001
Concentration unit: mg/kg milligram(s)/kilogram

Trade Name: Lantarel
Product Name: Lantarel
Pharmaceutical Form: Injection
INN or Proposed INN: METHOTREXATE SODIUM
CAS Number: 15475-56-6
Current Sponsor code: 9709.01.01
Other descriptive name: Lantarel
Concentration unit: mg milligram(s)

Trade Name: Arava
Product Name: Arava
Pharmaceutical Form: Tablet
INN or Proposed INN: LEFLUNOMIDE
CAS Number: 75706-12-6
Current Sponsor code: EU 1/99/118/007 – 008
Other descriptive name: A

Primary Outcome(s)

Secondary Objective: On the other hand it is interesting to find out which factors might serve as predictory values for reaching and maintaining a long lasting remission in spite of reduction and/or breaking off of therapy.

Primary end point(s): Number of patients in each group still in remission after twelve months (DAS 28 < 2,6)

Main Objective: The current concept of RA-therapy is remission, which is defined by reaching a disease activity score counted in 28 joints of the body (DAS 28) of less than 2,6 as a main target.
Rheumatoid Arthritis nowadays is being treated increasingly successful, due to better treatment with standard medications (dosage until limit, combination of therapies), due to quicker and more flexible therapy schemes (early start of treatment, close mashed therapy monitoring and due to introduction of new preparations. About 30% of RA patients reach clinical remission of RA.
Yet it is still unclear, if and for how long a patient in long lasting and stable remission is to continue therapy or whether it is possible to reduce medication without risking a relapse of the disease.
This study means on one hand to examine the possibility of a reduction of therapy or even a breaking off therapy in RA patients in long lasting remission.

Secondary ID(s)

UKER00109STUM3

Ethics review

Status: Approved
Approval date: 11/05/2010
Contact: