World Health Organization site
Skip Navigation Links

Main
Note: This record shows only 22 elements of the WHO Trial Registration Data Set. To view changes that have been made to the source record, or for additional information about this trial, click on the URL below to go to the source record in the primary register.
Register: EUCTR
Last refreshed on: 16 December 2019
Main ID:  EUCTR2017-003037-28-NL
Date of registration: 22/07/2019
Prospective Registration: Yes
Primary sponsor: University Medical Center Utrecht
Public title: Efficacy of TOcilizumab in comparison to Prednisone In Rheumatoid Arthritis patients with insufficient response to disease modifying anti-rheumatic drugs.
Scientific title: Efficacy of TOcilizumab in comparison to Prednisone In Rheumatoid Arthritis patients with insufficient response to disease modifying anti-rheumatic drugs. - TOPIRA
Date of first enrolment: 02/10/2019
Target sample size: 120
Recruitment status: Authorised-recruitment may be ongoing or finished
URL:  https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2017-003037-28
Study type:  Interventional clinical trial of medicinal product
Study design:  Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no Number of treatment arms in the trial: 2  
Phase:  Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): yes
Countries of recruitment
Netherlands
Contacts
Name: Rheumatology & Clinical Immunology   
Address:  Heidelberglaan 100 3508GA Utrecht Netherlands
Telephone: 31887557357
Email: reumatologie-research@umcutrecht.nl
Affiliation:  University Medical Center Utrecht
Name: Rheumatology & Clinical Immunology   
Address:  Heidelberglaan 100 3508GA Utrecht Netherlands
Telephone: 31887557357
Email: reumatologie-research@umcutrecht.nl
Affiliation:  University Medical Center Utrecht
Key inclusion & exclusion criteria
Inclusion criteria:
• Able and willing to give written informed consent.
• Have sufficient knowledge of the Dutch language to be able to comply with the requirements of the study protocol.
• At least 18 years of age.
• Diagnosed as having RA and meeting the 2010 ACR/EULAR criteria for RA (Appendix A).
• Active RA defined by CDAI>10 and at least 1 swollen joint of the 28 joint count.
• On stable treatment with csDMARDs for = 8 weeks prior to the screening visit.
• Previous treatment with =2 csDMARDs OR previous treatment with =1 csDMARD in combination with a maximum of 1 TNF inhibitor (Wash out period: =2 weeks before first administration of study medication).

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 100
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range 20

Exclusion criteria:
• Having a contraindication for treatment with systemic GCs (as determined by the treating rheumatologist, in line with regular care).
• Having a contraindication for treatment with TCZ, as described in the Summary of Product Characteristics (SPC) Paragraph 4.3, page 33. ‘Special warnings and precautions for use’ as described in the SPC Paragraph 4.4, page 33, should be strictly followed.
• Use of systemic GCs (including i.a. GCs) within 4 weeks before the screening visit.
• Current use of a bDMARD or tsDMARD.
• Previous use of = 2 TNF-inhibitors.
• Previous use of any other bDMARD (beside 1 TNFi) or tsDMARD.
• Treatment with any investigational agent within 4 weeks prior to the screening visit.
• Having any other inflammatory rheumatic disease than RA, except for secondary Sjögren’s syndrome.
• Female who is pregnant (by anamnesis) or breast feeding, or considering becoming pregnant during the study period.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes
Health Condition(s) or Problem(s) studied
RA patients with active RA despite treatment with csDMARDs and previous use of max 1 TNFi.
MedDRA version: 20.0 Level: PT Classification code 10039073 Term: Rheumatoid arthritis System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders
Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]
Intervention(s)

Trade Name: RoActemra
Pharmaceutical Form: Solution for injection/infusion in pre-filled syringe
INN or Proposed INN: TOCILIZUMAB
CAS Number: 375823-41-9
Other descriptive name: TOCILIZUMAB
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 162-

Trade Name: Prednisone
Product Name: Prednisone
Pharmaceutical Form: Tablet
INN or Proposed INN: Prednisone
Current Sponsor code: Prednisone
Other descriptive name: PREDNISONE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 10-

Primary Outcome(s)

Secondary Objective: Secondary Efficacy Objective(s):
-To compare treatment strategies on drug retention (TCZ vs prednisone), as surrogate measure of drug efficacy and tolerability, and on drug treatment over time.
-To assess whether TCZ is more effective than prednisone in reaching different criteria for response, clinical remission, and low disease activity; and on reduction of radiographic progression.
-To compare treatments on costs and effects in a cost-effectiveness analysis

Secondary Patient-Reported Outcome Objectives:
-To assess whether TCZ is more effective than prednisone with regard to quality of life, functional ability, fatigue, sleep quality, and anxiety and depression.
-To compare treatments on costs and quality of life (utility) in a cost-utility analysis

Secondary Safety Objectives:
-To assess the occurrence of serious adverse events (SAEs), glucocorticoid-associated AEs and TCZ-associated AEs

Main Objective: To assess whether adding TCZ (subcutaneously 162 mg/week) to current csDMARD therapy is more effective in reducing disease activity than adding prednisone (orally 10 mg/day) in a usual care treat-to-target strategy in patients with insufficient response to DMARD therapy (DMARD-IR).
Primary end point(s): Change in CDAI from baseline to 12 months
Timepoint(s) of evaluation of this end point: Baseline to 12 months
Secondary Outcome(s)

Secondary end point(s): SECONDARY EFFICACY ENDPOINTS:
- Change in CDAI from baseline to 6 months
- Change in SDAI and change in DAS28 from baseline to 12 months.
- Drug retention rate, defined as the proportion of patients at 12 months on the treatment (TCZ/prednisone) to which they were allocated.
- Switch rate, defined as the proportion of patients who switched during the study period to treatment of the other arm.
- Average dose of TCZ or prednisone from baseline up to 12 months.
- ACR20, ACR50, and ACR70 response (using 28 joint counts), EULAR good or moderate response.
- Proportion of patients reaching a state of clinical remission at any time during the study defined by different criteria: CDAI=2.8 AND max 1 swollen joint of the 28 joint count, CDAI=2.8, SDAI=3, DAS28<2.6, and ACR-EULAR Boolean remission (defined by a tender joint count =1, a swollen joint count =1, a C-reactive protein =1mg/dL, and a patient global assessment =1 on a 0-10 scale).
- Time to reach a state of clinical remission defined by the criteria mentioned before.
- Proportion of patients reaching at least a state of low disease activity (defined by 2.8 - Change in Sharp/van der Heijde (SvH) score from baseline to 12 months
- Change in quality of life from baseline to 12 months (using the EQ5D)
- Change in functional ability from baseline to 12 months (using the Dutch consensus HAQ)
- Change in fatigue (using the FACIT-F), sleep quality (using the PSQI) and anxiety and depression (using the HADS) from baseline to 12 months.
- Direct medical (e.g. GP visits) and non-medical (e.g. travel expenses) costs as well as indirect costs (e.g. productivity loss) using the Health Care Utilisation and Work Productivity Questionnaire, and observed drug use and visits to the rheumatology clinic.
- Quality Adjusted Life Years (based on EQ5-D utility scores over time).

SECONDARY SAFETY ENDPOINTS:
- GC Toxicity Index (GTI) score at 6, 9 and 12 months
- The proportion of patients reaching =1 of the following categories of the GTI:
o Major increase in BMI
o Worsening of glucose tolerance despite treatment
o Worsening hypertension despite treatment
o Worsening hyperlipidemia despite treatment
o Decrease in bone density
o Moderate steroid myopathy or greater
o Moderate skin toxicity or greater
o Moderate neuropsychiatric symptoms or greater
o Grade 3 infection or greater
o Any category of the Specific List
- The proportion of patients experiencing =1 TCZ-associated AE
- The proportion of patients experiencing =1 SAE
- The number of AEs of the GTI, of TCZ-associated AE and of SAE per patient
Timepoint(s) of evaluation of this end point: As described in E.5.2.
Secondary ID(s)
TOPIRA
Source(s) of Monetary Support
Roche
University Medical Center Utrecht
Secondary Sponsor(s)
Ethics review
Status: Approved
Approval date:
Contact:
Results
Results available:
Date Posted:
Date Completed:
URL:
Disclaimer: Trials posted on this search portal are not endorsed by WHO, but are provided as a service to our users. In no event shall the World Health Organization be liable for any damages arising from the use of the information linked to in this section. None of the information obtained through use of the search portal should in any way be used in clinical care without consulting a physician or licensed health professional. WHO is not responsible for the accuracy, completeness and/or use made of the content displayed for any trial record.
Copyright - World Health Organization - Version 3.6 - Version history