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

Rheumatoid Arthritis Clinical Trial

— ARCTIC  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01205854
• Other study ID #: DIA2010-1
• Status: Completed
• Phase: Phase 4
• First received: September 16, 2010
• Last updated: April 15, 2015
• Start date: September 2010
• Est. completion date: April 2015

Study information

• Verified date: April 2015
• Source: Diakonhjemmet Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: Norway: Ethics Committee
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 238
• Est. completion date: April 2015
• Est. primary completion date: April 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Device:
• Ultrasonography
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.

Locations

Country	Name	City	State
Norway	Helse Sunnmøre HF, Dept. of Rheumatology	Ålesund
Norway	Helse Bergen HF, Haukeland University Hospital, Dept. of Rheumatology	Bergen
Norway	Vestre Viken HF, Dept. of Rheumatology	Drammen
Norway	Haugesund Sanitetsforening Revmatismesykehus	Haugesund
Norway	Revmatologene bendvold/Dovland	Kristiansand
Norway	Sørlandet Sykehus HF, Dept. of Rheumatology	Kristiansand
Norway	Sykehuset Østfold HF, Dept. of Rheumatology	Moss	Fredrikstad
Norway	Diakonhjemmet Sykehus AS, Dept. of Rheumatology	Oslo
Norway	Martina Hansens Hospital AS	Sandvika	Bærum
Norway	Universitetssykehuset Nord-Norge HF, Dept. of Rheumatology	Tromsø
Norway	St Olavs Hospital HF, Dept. of Rheumatology	Trondheim

Sponsors (11)

Lead Sponsor	Collaborator
Espen A. Haavardsholm	Abbott, Innovest, MSD Norway AS, Oslo University Hospital, Section for GCP, Pfizer, Roche Pharma AG, Smerud Medical Research International AS, The Norwegian Rheumatism Association, The Research Council of Norway, UCB Nordic A/S

Country where clinical trial is conducted

Norway, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	No
Secondary	American College of Rheumatology (ACR) response	Proportion of patients with ACR20, ACR50, ACR70 and ACR90 response.	24 months	No
Secondary	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	No
Secondary	European League Against Rheumatism (EULAR) response	EULAR good, moderate and non-response	24 months	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	EuroQol-5 Dimension (EQ-5D)	EQ-5D is a standardised instrument for use as a measure of health outcome.	24 months	No
Secondary	Health Assessment Questionnaire (HAQ-PROMIS)	The HAQ-PROMIS is a questionnaire evaluating the physical function in patients with RA.	24 months	No
Secondary	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	No
Secondary	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	Yes
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	American College of Rheumatology (ACR) response	Proportion of patients with ACR20, ACR50, ACR70 and ACR90 response.	12 months	No
Secondary	European League Against Rheumatism (EULAR) response	EULAR good, moderate and non-response	12 months	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	Health Assessment Questionnaire (HAQ-PROMIS)	The HAQ-PROMIS is a questionnaire evaluating the physical function in patients with RA.	12 months	No
Secondary	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	No
Secondary	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	Yes
Secondary	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	No
Secondary	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	No