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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
The Research Council of Norway
Smerud Medical Research International AS
Oslo University Hospital, Section for GCP
Innovest
Abbott
UCB NORDIC A/S
Pfizer
MSD Norway AS
Roche Pharma AG
The Norwegian Rheumatism Association
Information provided by (Responsible Party):
Espen A. Haavardsholm, Diakonhjemmet Sykehus
ClinicalTrials.gov Identifier:
NCT01205854
First received: September 16, 2010
Last updated: June 26, 2013
Last verified: June 2013
  Purpose

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.


Condition Intervention Phase
Rheumatoid Arthritis
Device: Ultrasonography
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Aiming for Remission in Rheumatoid Arthritis: a Randomized Trial Examining the Benefit of Ultrasonography in a Clinical TIght Control Regimen

Resource links provided by NLM:


Further study details as provided by Diakonhjemmet Hospital:

Primary Outcome Measures:
  • Complete clinical Disease Activity Score (DAS) remission [ Time Frame: 24 months ] [ Designated as safety issue: No ]

    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)


Secondary Outcome Measures:
  • Magnetic Resonance Imaging (MRI) of dominant hand [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    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.

  • American College of Rheumatology (ACR) response [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    Proportion of patients with ACR20, ACR50, ACR70 and ACR90 response.

  • Remission [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    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

  • European League Against Rheumatism (EULAR) response [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    EULAR good, moderate and non-response

  • Work performance [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    1. Absenteeism (work time missed)
    2. Presenteeism (impairment at work / reduced on-the-job effectiveness)
    3. Work productivity loss (overall work impairment / absenteeism plus presenteeism)
    4. Activity Impairment

  • Conventional radiography [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    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.

  • The RA Impact of Disease (RAID) score [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    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%).

  • EuroQol-5 Dimension (EQ-5D) [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    EQ-5D is a standardised instrument for use as a measure of health outcome.

  • Health Assessment Questionnaire (HAQ-PROMIS) [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    The HAQ-PROMIS is a questionnaire evaluating the physical function in patients with RA.

  • Medical Outcomes Study Short-Form 36-item (SF-36) [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    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.

  • Dual Energy X-ray Absorptiometry (DEXA) of spine and hip [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]
    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.

  • Disease Activity Score (DAS) [ Time Frame: 24 months ] [ Designated as safety issue: No ]

    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


  • Ultrasonography (synovitis) [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    36 joints and 2 tendons will be scored for both grey scale and power doppler synovitis on a 0-3 scale.

  • Magnetic Resonance Imaging (MRI) of dominant hand [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    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.

  • American College of Rheumatology (ACR) response [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    Proportion of patients with ACR20, ACR50, ACR70 and ACR90 response.

  • European League Against Rheumatism (EULAR) response [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    EULAR good, moderate and non-response

  • Remission [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    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

  • Work performance [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    1. Absenteeism (work time missed)
    2. Presenteeism (impairment at work / reduced on-the-job effectiveness)
    3. Work productivity loss (overall work impairment / absenteeism plus presenteeism)
    4. Activity Impairment

  • Conventional radiography [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    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.

  • The RA Impact of Disease (RAID) score [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    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%).

  • Health Assessment Questionnaire (HAQ-PROMIS) [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    The HAQ-PROMIS is a questionnaire evaluating the physical function in patients with RA.

  • Medical Outcomes Study Short-Form 36-item (SF-36) [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    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.

  • Dual Energy X-ray Absorptiometry (DEXA) of spine and hip [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    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.

  • Ultrasonography (synovitis) [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    36 joints and 2 tendons will be scored for both grey scale and power doppler synovitis on a 0-3 scale.

  • Disease Activity Score (DAS) [ Time Frame: 12 months ] [ Designated as safety issue: No ]

    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



Estimated Enrollment: 240
Study Start Date: September 2010
Estimated Study Completion Date: September 2015
Estimated Primary Completion Date: September 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
No Intervention: Conventional clinical and laboratory assessment
Experimental: Conventional assessment plus ultrasonography 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.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01205854

Locations
Norway
Martina Hansens Hospital AS
Sandvika, Bærum, Norway, 1306
Sykehuset Østfold HF, Dept. of Rheumatology
Moss, Fredrikstad, Norway, 1603
Helse Bergen HF, Haukeland University Hospital, Dept. of Rheumatology
Bergen, Norway, 5021
Vestre Viken HF, Dept. of Rheumatology
Drammen, Norway, 3004
Haugesund Sanitetsforening Revmatismesykehus
Haugesund, Norway, 5504
Revmatologene bendvold/Dovland
Kristiansand, Norway, 4611
Sørlandet Sykehus HF, Dept. of Rheumatology
Kristiansand, Norway, 4604
Revmatismesykehuset AS, Dept. of Rheumatology
Lillehammer, Norway, 2609
Diakonhjemmet Sykehus AS, Dept. of Rheumatology
Oslo, Norway, 0319
Universitetssykehuset Nord-Norge HF, Dept. of Rheumatology
Tromsø, Norway, 9038
St Olavs Hospital HF, Dept. of Rheumatology
Trondheim, Norway, 7006
Helse Sunnmøre HF, Dept. of Rheumatology
Ålesund, Norway, 6026
Sponsors and Collaborators
Espen A. Haavardsholm
The Research Council of Norway
Smerud Medical Research International AS
Oslo University Hospital, Section for GCP
Innovest
Abbott
UCB NORDIC A/S
Pfizer
MSD Norway AS
Roche Pharma AG
The Norwegian Rheumatism Association
Investigators
Study Director: Tore K Kvien, MD, PhD Diakonhjemmet Hospital AS
  More Information

No publications provided

Responsible Party: Espen A. Haavardsholm, Post. doctoral Researcher, MD Ph.D., Diakonhjemmet Sykehus
ClinicalTrials.gov Identifier: NCT01205854     History of Changes
Other Study ID Numbers: DIA2010-1
Study First Received: September 16, 2010
Last Updated: June 26, 2013
Health Authority: Norway: Ethics Committee

Keywords provided by Diakonhjemmet Hospital:
rheumatoid arthritis
ultrasonography
remission
imaging remission
tight control
treat to target

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases

ClinicalTrials.gov processed this record on September 22, 2014