E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10039073 |
E.1.2 | Term | Rheumatoid arthritis |
E.1.2 | System Organ Class | 10028395 - Musculoskeletal and connective tissue disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
a)To assess the effectiveness, safety and cost-effectiveness of 2 years of low-dose GC therapy (5 mg/day) compared to placebo as co-treatment for elderly RA patients in a pragmatic randomized trial b)Study medication adherence through a medication packaging solution, and test the effectiveness of smart device technology to improve adherence
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
test the effectiveness of smart device technology to improve adherence |
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E.3 | Principal inclusion criteria |
RA according to the 1987 or 2010 classification criteria of the American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR) (Aletaha D 2010);
Inadequate disease control, as evidenced by a 28-joint disease activity score (DAS28) of ≥ 2.60. For eligibility, the DAS28 can be calculated with ESR or CRP, and also recalculated from the DAS of 44 joints. A DAS28 may be calculated with clinical and lab assessments obtained no more than 4 weeks before the baseline visit.
age ≥ 65 years.
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E.4 | Principal exclusion criteria |
Change, stop or start of antirheumatic treatment in the last month prior to eligibility assessment, including methotrexate, sulfasalazine, hydroxychloroquine, leflunomide, azathioprine, intramuscular and oral gold, cyclosporine, biologic agents including anti-TNF, anakinra, abatacept, rituximab, tocilizumab (temporary exclusion); Treatment with systemic GC: oral or parenteral GC with a cumulative prednisolone equivalent dose of 200 mg or higher in the last 3 months; Treatment with any GC (oral, intra-articular, intravenous or intramuscular) in the last 30 days (temporary exclusion); Exposure to investigational therapy in the last three months; Current participation in another clinical trial; Major surgery, donation or loss of approximately 500 ml blood within 4 weeks prior to the screening visit (temporary exclusion) Absolute contraindication to low-dose prednisolone, as determined by the treating physician, such as: uncontrolled chronic infections, diabetes mellitus, hypertension, osteoporosis. When these conditions are under control (e.g. with antiosteoporosis drugs, antihypertensive drugs) these patients can enter; Absolute contraindication to Calcium and/or Vitamin D supplement as determined by the treating physician, such as: hyperparathyroidism (when insufficiently treated); Uncontrolled comorbid conditions, short life span, etc. as determined by the treating physician. Absolute indication to start with oral or intravenous GC, according to the treating physician; Inability to comply with medical instructions or inability to assess major outcomes at 6-monthly visits, in the assessment of the treating physician.
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E.5 End points |
E.5.1 | Primary end point(s) |
Signs and symptoms: the time-averaged mean value of the DAS28. To measure safety, the primary endpoint is the total number of patients experiencing at least one serious adverse event, or one clinical event related to the disease or its therapy. Other major outcomes are cost-effectiveness, cost-utility, and medication adherence.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Baseline, 3, 6, 12, 18 and 24 months |
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E.5.2 | Secondary end point(s) |
Damage progression: 2-year change in total Sharp/van der Heijde damage score of hands and forefeet radiographs. WHO-ILAR core set of RA outcome measures, including pain, patient and physician global assessment, physical disability, joint counts (swollen joints and tender joints), acute phase reactants (C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR)), and radiographs of hands and forefeet at 0 and 2 years Severity and duration of morning stiffness Fatigue SF36 - The Short Form 36-item Health Survey, a questionnaire about QoL RA Impact of Disease (RAID) tool – The RAID is a validated questionnaire assessing the seven most important domains of impact of RA on the patients Health Assessment Questionnaire (HAQ) Cost questionnaire, including; Activity limitation (part of cost questionnaire); Work disability (for those holding a paid job, part of cost questionnaire) Utility/Quality-adjusted life years (QALY): Euro-QoL in 5 dimensions (EQ-5D)
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Baseline, 3, 6, 9, 12, 15, 18, 21 and 24 months |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | Yes |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 29 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 6 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 6 |