Aiming for Remission in Rheumatoid Arthritis (RA) - the ARCTIC Trial

Study Overview
=================
Brief Summary
-----------------
The ultimate goal of treatment in early rheumatoid arthritis (RA) is remission, i.e. an absence of signs and symptoms of the disease. However, the optimal way of reaching this goal is not known. Ultrasonography (US) is an imaging modality which application is rapidly growing. It has a number of advantages over other advanced imaging techniques such as magnetic resonance imaging (MRI), including low cost, good accessibility, and ability to scan many joints in a short period of time. However, the additional benefit of using this modality in terms of patient outcomes has not been demonstrated. Thus, clarification is needed if the use of US leads to better care for RA patients. This study will assess if the use of a treatment strategy incorporating information from ultrasonography assessment will allow for better outcomes of patients with RA, than a strategy based on clinical and laboratory assessments alone.

Official Title
-----------------
Aiming for Remission in Rheumatoid Arthritis: a Randomized Trial Examining the Benefit of Ultrasonography in a Clinical TIght Control Regimen

Conditions
-----------------
Rheumatoid Arthritis

Intervention / Treatment
-----------------
* Device: Ultrasonography


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion criteria (all): Male or non-pregnant, non-nursing female > 18 years of age and < 75 years of age Patients classified as having RA (according to new ACR/EULAR criteria) Disease duration less than 2 years (defined as time from 1st joint swelling) The treating rheumatologist decides the patient requires treatment with a Disease Modifying Anti-Rheumatic Drug (DMARD) The patient has taken no prior DMARD Patients able and willing to give written informed consent and comply with the requirements of the study protocol Exclusion Criteria (any): Abnormal renal function (serum creatinine > 142 µmol/L in female and > 168 µmol/L in male) Abnormal liver function, active or recent hepatitis, cirrhosis Major co-morbidities like severe malignancies, severe diabetic mellitus, severe infections, uncontrollable hypertension, severe cardiovascular disease and/or severe respiratory diseases. Leukopenia and/or thrombocytopenia Inadequate birth control conception, pregnancy, and/or breastfeeding Indications of active tuberculosis Psychiatric or mental disorders, alcohol abuse or other abuse of substances, language barriers or other factors which makes adherence to the study protocol impossible

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Conventional clinical and laboratory assessment<br> | |
| Experimental: Conventional assessment plus ultrasonography<br> | Device: Ultrasonography<br>* Standardized ultrasonographic assessment of 32 joints, assessed for both grey scale synovitis and power doppler signal, at each visit. Dose escalations based on DAS response in combination with change in US score. All joints with US Power Doppler signal are targets for intra articular injections.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete clinical Disease Activity Score (DAS) remission | Specifically, the primary endpoint will be the proportion of patients with all the following criteria met at the end of the study (at 24 months): DAS score < 1.6 at visits 11, 12 and 13 (after 16, 20 and 24 months) Absence of swollen joints at visits 11, 12 and 13 (after 16, 20 and 24 months) No radiological progression between visit 11 (16 months) and visit 13 (24 months) | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Magnetic Resonance Imaging (MRI) of dominant hand | MRIs of dominant hand are scored according to the Rheumatoid Arthritis Magnetic Resonance Imaging Score (RAMRIS) for synovitis, bone marrow edema and erosions, and Haavardsholm tenosynovitis score, as well as a novel joint space narrowing score will be applied. | 24 months | 
| American College of Rheumatology (ACR) response | Proportion of patients with ACR20, ACR50, ACR70 and ACR90 response. | 24 months | 
| Remission | Various definitions of remission will be calculated, including DAS-remission, ACR-remission, Simplified Diseases Activity Index (SDAI) remission and Clinical Disease Activity Index (CDAI) remission | 24 months | 
| European League Against Rheumatism (EULAR) response | EULAR good, moderate and non-response | 24 months | 
| Work performance | Absenteeism (work time missed) Presenteeism (impairment at work / reduced on-the-job effectiveness) Work productivity loss (overall work impairment / absenteeism plus presenteeism) Activity Impairment | 24 months | 
| Conventional radiography | Radiographs of hands (posterior/anterior) and foot (anterior/posterior) will be taken at baseline, 3, 6, 12, 16 and 24 months. The modified Sharp van der Heijde Score (vdHSS) will be calculated, including an erosion score and a joint space narrowing score. | 24 months | 
| The RA Impact of Disease (RAID) score | The RAID includes seven domains with the following relative weights: pain (21%), functional disability (16%), fatigue (15%), emotional well-being (12%), sleep (12%), coping (12%) and physical well-being (12%). | 24 months | 
| EuroQol-5 Dimension (EQ-5D) | EQ-5D is a standardised instrument for use as a measure of health outcome. | 24 months | 
| Health Assessment Questionnaire (HAQ-PROMIS) | The HAQ-PROMIS is a questionnaire evaluating the physical function in patients with RA. | 24 months | 
| Medical Outcomes Study Short-Form 36-item (SF-36) | The SF-36 is a multi-purpose, short-form health survey with only 36 questions. It yields an 8-scale profile of functional health and well-being scores as well as psychometrically-based physical and mental health summary measures and a preference-based health utility index. | 24 months | 
| Dual Energy X-ray Absorptiometry (DEXA) of spine and hip | Bone density measurements (DEXA hip and spine, both Z- and T-scores as well as bone mineral density) will be performed at baseline and after 12 and 24 months. | 24 months | 
| Disease Activity Score (DAS) | The DAS is a composite score that includes the Ritchie articular index (RAI), the 44- swollen joint counts (SJC-44), the Erythrocyte Sedimentation Rate (ESR) and a general health (GH) assessment on a Visual Analogue Scale (VAS). The DAS is calculated as follows: DAS = 0.54*sqrt(RAI) + 0.065*(SJC-44) + 0.33*Ln(ESR) + 0.0072*GH | 24 months | 
| Ultrasonography (synovitis) | 36 joints and 2 tendons will be scored for both grey scale and power doppler synovitis on a 0-3 scale. | 24 months | 
| Magnetic Resonance Imaging (MRI) of dominant hand | MRIs of dominant hand are scored according to the Rheumatoid Arthritis Magnetic Resonance Imaging Score (RAMRIS) for synovitis, bone marrow edema and erosions, and Haavardsholm tenosynovitis score, as well as a novel joint space narrowing score will be applied. | 12 months | 
| American College of Rheumatology (ACR) response | Proportion of patients with ACR20, ACR50, ACR70 and ACR90 response. | 12 months | 
| European League Against Rheumatism (EULAR) response | EULAR good, moderate and non-response | 12 months | 
| Remission | Various definitions of remission will be calculated, including DAS-remission, ACR-remission, Simplified Diseases Activity Index (SDAI) remission and Clinical Disease Activity Index (CDAI) remission | 12 months | 
| Work performance | Absenteeism (work time missed) Presenteeism (impairment at work / reduced on-the-job effectiveness) Work productivity loss (overall work impairment / absenteeism plus presenteeism) Activity Impairment | 12 months | 
| Conventional radiography | Radiographs of hands (posterior/anterior) and foot (anterior/posterior) will be taken at baseline, 3, 6 and 12 months. The modified Sharp van der Heijde Score (vdHSS) will be calculated, including an erosion score and a joint space narrowing score. | 12 months | 
| The RA Impact of Disease (RAID) score | The RAID includes seven domains with the following relative weights: pain (21%), functional disability (16%), fatigue (15%), emotional well-being (12%), sleep (12%), coping (12%) and physical well-being (12%). | 12 months | 
| Health Assessment Questionnaire (HAQ-PROMIS) | The HAQ-PROMIS is a questionnaire evaluating the physical function in patients with RA. | 12 months | 
| Medical Outcomes Study Short-Form 36-item (SF-36) | The SF-36 is a multi-purpose, short-form health survey with only 36 questions. It yields an 8-scale profile of functional health and well-being scores as well as psychometrically-based physical and mental health summary measures and a preference-based health utility index. | 12 months | 
| Dual Energy X-ray Absorptiometry (DEXA) of spine and hip | Bone density measurements (DEXA hip and spine, both Z- and T-scores as well as bone mineral density) will be performed at baseline and after 12 and 24 months. | 12 months | 
| Ultrasonography (synovitis) | 36 joints and 2 tendons will be scored for both grey scale and power doppler synovitis on a 0-3 scale. | 12 months | 
| Disease Activity Score (DAS) | The DAS is a composite score that includes the Ritchie articular index (RAI), the 44- swollen joint counts (SJC-44), the Erythrocyte Sedimentation Rate (ESR) and a general health (GH) assessment on a Visual Analogue Scale (VAS). The DAS is calculated as follows: DAS = 0.54*sqrt(RAI) + 0.065*(SJC-44) + 0.33*Ln(ESR) + 0.0072*GH | 12 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
rheumatoid arthritis, ultrasonography, remission, imaging remission, tight control, treat to target