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Arthroscopic Synovectomy of the Wrist in Inflammatory Arthritis (ARCTIC)

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ClinicalTrials.gov Identifier: NCT04755127
Recruitment Status : Recruiting
First Posted : February 15, 2021
Last Update Posted : February 25, 2021
Sponsor:
Information provided by (Responsible Party):
Maasstad Hospital

Tracking Information
First Submitted Date  ICMJE January 27, 2021
First Posted Date  ICMJE February 15, 2021
Last Update Posted Date February 25, 2021
Actual Study Start Date  ICMJE January 1, 2021
Estimated Primary Completion Date January 1, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 23, 2021)
Patient-Rated Wrist evaluation (PRWE) [ Time Frame: 3 months ]
15-item questionnaire scoring pain and wrist function on a scale from 0-100, with a higher score indicating worse outcome.
Original Primary Outcome Measures  ICMJE
 (submitted: February 11, 2021)
Patient-Rated Wrist evaluation (PRWE) [ Time Frame: 3 months ]
15-item questionnaire evaluating pain and function of the wrist
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 23, 2021)
  • Patient-Rated Wrist evaluation (PRWE) [ Time Frame: 6 and 12 months ]
    15-item questionnaire scoring pain and wrist function on a scale from 0-100, with a higher score indicating worse outcome.
  • Wrist ultrasound [ Time Frame: 3 months ]
    Resolution of ultrasound (US) arthritis as defined by grey scale (B-mode) and power Doppler after three months compared to baseline measurement. Grey scale uses a two-dimensional image to visualize structural changes like synovial hypertrophy and bone erosions. Power Doppler mode can assess joint inflammatory activity by detecting pathological synovial blood flow. The EULAR-OMERACT (Outcome Measures in Rheumatology Clinical Trials) combined scoring system includes both greyscale and power Doppler and will be used to score arthritis in this study. Ultrasound has demonstrated greater sensitivity than clinical assessment and conventional radiography for detecting synovitis in RA target joints. Also, US signs of synovitis were found predictive for flare and failure of DMARD therapy, despite clinical remission. Furthermore, ultrasound techniques are low-invasive, inexpensive and require no radiation.
  • Wrist X-ray [ Time Frame: 12 months ]
    Standard (plain) radiographs of the wrist at baseline and after twelve months. Arthritis on radiographs will be graded using the Modified Larsen grading system. This system grades wrist arthritis on a score of 0 to 5, 5 indicating the most joint abnormalities.
  • NRS pain score [ Time Frame: 2, 4 and 6 weeks, 3, 6 and 12 months ]
    Numeric Rating Scale (NRS) pain score at baseline two, four and six weeks (by phone), and at three, six and twelve months (digitally). A score of 0 implies no pain and 10 the worst possible pain.
  • Range of motion [ Time Frame: 3, 6 and 12 months ]
    Range of motion (ROM) of the wrist at baseline, three, six and twelve months. ROM will be measured actively with a goniometer and includes pronation, supination, ulnar and radial deviation and palmar and dorsal flexion.
  • Grip strength [ Time Frame: 3, 6 and 12 months ]
    Grip strength of the wrist at baseline, three, six and twelve months. Grip strength will be measured using a dynamometer as the mean of three measurements.
  • DAS 28 [ Time Frame: 3, 6 and 12 months ]
    EULAR response rate and Disease Activity Score (DAS28) at baseline, three, six and twelve months. The DAS28 is a measure of disease activity in rheumatoid arthritis in which 28 joints are examined for swelling and tenderness, combined with global pain scores and blood markers (www.DAS28-score.nl). The EULAR response rate measures responsiveness to anti-rheumatic treatment and is derived from the DAS28 score
  • EQ-5D [ Time Frame: 3, 6 and 12 months ]
    EuroQol 5D (EQ-5D) at baseline, three, six and twelve months. The EQ-5D is a standardized questionnaire scoring quality of life on five different levels, on a scale from 0-100.
  • iPCQ questionnaire [ Time Frame: 3, 6 and 12 months ]
    Institute for Medical Technology Assessment (iMTA) Productivity Cost Questionnaire (iPCQ) at baseline, three, six and twelve months. The iPCQ is a standardized instrument for measuring and valuing health related productivity losses. This wil be used for the cost effectiveness analysis.
  • iMCQ questionnaire [ Time Frame: 3, 6 and 12 months ]
    Institute for Medical Technology Assessment (iMTA) Medical Consumption Questionnaire (iMCQ) at baseline, three, six and twelve months. The iMCQ is a standardized instrument for measuring medical costs. The iMCQ includes questions related to frequently occurring contacts with health care providers, medication use and home care. This wil be used for the cost effectiveness analysis.
  • ESR [ Time Frame: 3, 6 and 12 months ]
    Laboratory test: erythrocyte sedimentation rate (ESR) at baseline and three, six and twelve months (part of the routine clinical care).
  • CRP [ Time Frame: 3, 6 and 12 months ]
    Laboratory tests: C-reactive protein (CRP) at baseline and three, six and twelve months (part of the routine clinical care).
  • Adverse events [ Time Frame: One year ]
    Adverse events (AEs) (including glucocorticoid related AEs), AEs leading to withdrawal, AEs leading to discontinuation of medication, and AEs due to infusion reactions.
Original Secondary Outcome Measures  ICMJE
 (submitted: February 11, 2021)
  • PRWE [ Time Frame: 6 and 12 months ]
  • Wrist ultrasound [ Time Frame: 3 months ]
    Resolution of ultrasound (US) arthritis as defined by grey scale (B-mode) and power Doppler after three months compared to baseline measurement. Grey scale uses a two-dimensional image to visualize structural changes like synovial hypertrophy and bone erosions. Power Doppler mode can assess joint inflammatory activity by detecting pathological synovial blood flow. The EULAR-OMERACT (Outcome Measures in Rheumatology Clinical Trials) combined scoring system includes both greyscale and power Doppler and will be used to score arthritis in this study. Ultrasound has demonstrated greater sensitivity than clinical assessment and conventional radiography for detecting synovitis in RA target joints. Also, US signs of synovitis were found predictive for flare and failure of DMARD therapy, despite clinical remission. Furthermore, ultrasound techniques are low-invasive, inexpensive and require no radiation.
  • Wrist X-ray [ Time Frame: 12 months ]
    Standard (plain) radiographs of the wrist at baseline and after twelve months. Arthritis on radiographs will be graded using the Modified Larsen grading system. This system grades wrist arthritis on a score of 0 to 5, 5 indicating the most joint abnormalities.
  • NRS pain score [ Time Frame: 2, 4 and 6 weeks, 3, 6 and 12 months ]
    Numeric Rating Scale (NRS) pain score at baseline two, four and six weeks (by phone), and at three, six and twelve months (digitally). A score of 0 implies no pain and 10 the worst possible pain.
  • Range of motion [ Time Frame: 3, 6 and 12 months ]
    Range of motion (ROM) of the wrist at baseline, three, six and twelve months. ROM will be measured actively with a goniometer and includes pronation, supination, ulnar and radial deviation and palmar and dorsal flexion.
  • Grip strength [ Time Frame: 3, 6 and 12 months ]
    Grip strength of the wrist at baseline, three, six and twelve months. Grip strength will be measured using a dynamometer as the mean of three measurements.
  • DAS 28 [ Time Frame: 3, 6 and 12 months ]
    EULAR response rate and Disease Activity Score (DAS28) at baseline, three, six and twelve months. The DAS28 is a measure of disease activity in rheumatoid arthritis in which 28 joints are examined for swelling and tenderness, combined with global pain scores and blood markers (www.DAS28-score.nl). The EULAR response rate measures responsiveness to anti-rheumatic treatment and is derived from the DAS28 score
  • EQ-5D [ Time Frame: 3, 6 and 12 months ]
    EuroQol 5D (EQ-5D) at baseline, three, six and twelve months. The EQ-5D is a standardized questionnaire scoring quality of life on five different levels, on a scale from 0-100.
  • iPCQ questionnaire [ Time Frame: 3, 6 and 12 months ]
    Institute for Medical Technology Assessment (iMTA) Productivity Cost Questionnaire (iPCQ) at baseline, three, six and twelve months. The iPCQ is a standardized instrument for measuring and valuing health related productivity losses. This wil be used for the cost effectiveness analysis.
  • iMCQ questionnaire [ Time Frame: 3, 6 and 12 months ]
    Institute for Medical Technology Assessment (iMTA) Medical Consumption Questionnaire (iMCQ) at baseline, three, six and twelve months. The iMCQ is a standardized instrument for measuring medical costs. The iMCQ includes questions related to frequently occurring contacts with health care providers, medication use and home care. This wil be used for the cost effectiveness analysis.
  • ESR [ Time Frame: 3, 6 and 12 months ]
    Laboratory test: erythrocyte sedimentation rate (ESR) at baseline and three, six and twelve months (part of the routine clinical care).
  • CRP [ Time Frame: 3, 6 and 12 months ]
    Laboratory tests: C-reactive protein (CRP) at baseline and three, six and twelve months (part of the routine clinical care).
  • Adverse events [ Time Frame: One year ]
    Adverse events (AEs) (including glucocorticoid related AEs), AEs leading to withdrawal, AEs leading to discontinuation of medication, and AEs due to infusion reactions.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Arthroscopic Synovectomy of the Wrist in Inflammatory Arthritis
Official Title  ICMJE ARthroscopiC SynovecTomy Versus Intra-Articular Injection of Corticosteroids for the Management of Therapy Refractory Psoriatic or Rheumatoid Arthritis of the Wrist: a Randomized Controlled Trial
Brief Summary

Rationale: Psoriatic (PsA) and rheumatoid arthritis (RA) are inflammatory joint diseases that often involve the wrist and may result in progressive joint destruction followed by impaired wrist function and reduced quality of life. The first line treatment usually consists of conventional Disease-Modifying Anti-Rheumatic Drugs (cDMARDs) along with bridging therapy using systemic corticosteroids or intra-articular corticosteroids in case of limited joint disease. After initiation therapy, intra-articular corticosteroids are often utilized as they provide rapid dampening of joint inflammation in case of a flare-up of disease activity (mono- or oligoarthritis). However, a substantial part of these patients clinically respond poorly or not at all. Alternatively, arthroscopic synovectomy may provide substantial relieve of symptoms, improve functionality, slow down disease progression and prevent joint destruction, as earlier studies have suggested. Prospective randomized studies are needed to confirm these findings. Moreover, they may prevent the need for expensive biological Disease-Modifying Anti-Rheumatic Drugs (bDMARDs) and assist in guiding therapeutic strategies in the long run, through collecting and analysing valuable synovial biopsies. Wrist arthroscopy is a routine procedure in the participating centres with only minor complications and fast recovery.

Objective: To compare arthroscopic synovectomy with deposition of intra-articular corticosteroids (DIACS) versus intra-articular injection of corticosteroids (IACSI) in RA and PsA patients with mono- or oligoarthritis of the wrist that is refractory to cDMARD therapy.

Study design: Multi-centre randomized controlled trial conducted in the Maasstad Hospital and Spijkenisse Medisch Centrum (SMC).

Study population: Patients with active RA or PsA and bDMARD-naive, who develop a localized flare of disease activity (mono- or oligoarthritis) that involves the wrist, defined as an increase in DAS28 > 1.2 or > 0.6 if DAS28 ≥ 3.2 compared to the last DAS28 measurement (maximum six months before) and that is refractory to systemic cDMARD for at least three months, defined as no response on the European League Against Rheumatism (EULAR) response criteria.

Intervention: This study will randomize between IACSI of the wrist (control) and arthroscopic synovectomy of the wrist combined with DIACS (intervention). During arthroscopy synovial biopsies will be collected and stored for later analysis of the functional and histological characteristics of the synovium (beyond the scope of this study).

Main study parameters/endpoints: Primary outcome is the change in Patient-Rated Wrist Evaluation (PRWE) score from randomization to three months of follow-up. The PRWE is a validated, fifteen-item self-reported questionnaire rating wrist pain and function. Secondary outcomes are resolution of wrist arthritis measured by ultrasound, standard wrist radiographs, DAS28, EULAR response rate, Visual Analogue Scale (VAS), EQ-5D quality of life questionnaire, iMTA Productivity Cost Questionnaire (iPCQ), iMTA Medical Consumption Questionnaire (iMCQ), cost effectiveness analyses (CEA), physical examination, adverse events (AE) and laboratory results. Follow-up visits are scheduled at three, six and twelve months after intervention.

Nature and extent of the burden and risks associated with study participation:

Both study arms include standard treatment of care. Wrist arthroscopy is a standard treatment for wrist arthritis and often implemented for other intra-articular wrist pathology. The risks include infection, neurovascular damage and articular surface damage. Nevertheless, wrist arthroscopy is a well-established and safe technique. Reduction of risks will be done according to inclusion and exclusion criteria. If complications arise, the treating physician will proportionate the adequate treatment according to the current protocols based on the published literature. Patients will be asked to return at three, six and twelve months. These visits are standard of care following the rheumatic arthritis protocol. Patients will be asked to complete questionnaires at baseline and at three follow-up moments. These will take 160 minutes in total. The arthroscopy group will return between ten to fourteen days for wound inspection. All patient will be contacted by telephone at two, four and six weeks for VAS pain scores.

Expected results: We expect that arthroscopic synovectomy followed by DIACS will lead to significantly more improvement in PRWE scores compared to IACSI three months after intervention. Furthermore, we anticipate that wrist arthroscopy will result in lower pain scores, better joint mobility, better response on EULAR score, sustained resolution of arthritis on ultrasound, less joint damage on radiographs and is more cost-effective after one-year analysis.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
non-blinded randomized controlled trial
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Wrist Arthritis
  • Psoriatic Arthritis
  • Rheumatoid Arthritis
  • Surgery
Intervention  ICMJE
  • Procedure: Arthroscopic synovectomy of the wrist
    Wrist arthroscopy in day surgery setting with debulking of synovitis, inspection of cartilage, ligament, tendon and bone damage, collection of synovial biopsies and deposition of intra-articular corticosteroids (40mg triamcinolone acetonide)
  • Drug: Intra-articular corticosteroid injection
    Injection with 40mg triamcinolone acetonide (kenacort) in the wrist
Study Arms  ICMJE
  • Active Comparator: Intra-articular corticosteroid injection
    Injection with 40mg triamcinolone acetonide (kenacort) in the wrist
    Intervention: Drug: Intra-articular corticosteroid injection
  • Experimental: arthroscopic synovectomy
    Wrist arthroscopy in day surgery setting with debulking of synovitis, inspection of cartilage, ligament, tendon and bone damage, collection of synovial biopsies and deposition of intra-articular corticosteroids (40mg triamcinolone acetonide)
    Intervention: Procedure: Arthroscopic synovectomy of the wrist
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: February 11, 2021)
80
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE September 1, 2023
Estimated Primary Completion Date January 1, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion criteria In order to be eligible to participate in this study, a subject must meet all of the following criteria:

  • Male and female patients with age ≥ 18 years
  • Subjects able and willing to give written informed consent (or legally acceptable representative or impartial witness when applicable) and is available for entire study
  • Patients meet the criteria of either group below:

Group 1. Inclusion criteria RA patients:

  • Patients that are diagnosed with RA according to the revised 2010 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) Rheumatoid Arthritis Classification Criteria (table 1)
  • Patients are experiencing an exacerbation defined as an increase in DAS28 > 1.2 or > 0.6 if DAS28 ≥ 3.2 compared to last DAS28 measurement (maximum six months before)
  • The exacerbation is refractory to systemic cDMARDs for at least three months, defined as 'no response' according to the EULAR response criteria (table 2)
  • Wrist arthritis, that is diagnosed clinically, is the predominant symptom

Group 2. Inclusion criteria PsA patients:

  • Patients that are diagnosed with PsA according to the Classification Criteria for Psoriatic Arthritis (CASPAR) criteria (table 3)
  • Patients are experiencing an exacerbation defined as an increase in DAS28 > 1.2 or > 0.6 if DAS28 ≥ 3.2 compared to last DAS28 measurement (maximum six months before)
  • The exacerbation is refractory to systemic cDMARDs for at least three months, defined as 'no response' according to the EULAR response criteria (table 2)
  • Wrist arthritis, that is diagnosed clinically, is the predominant symptom

Exclusion criteria A potential subject who meets any of the following criteria will be excluded from participation in this study:

  • Previous or current treatment with biological (b) DMARDs
  • Current inflammatory joint disease other than RA or PsA (e.g. gout, reactive arthritis, Lyme disease)
  • Subjects who are pregnant or intend to become pregnant during the study
  • Intra-articular corticosteroids injection in the wrist in the last 6 months
  • Previous wrist surgery
  • Severe osteoarthritis with malformations of the wrist
  • Congenital abnormalities of wrist function or motion
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Philip d'Ailly, MD daillyp@maastadziekenhuis.nl
Listed Location Countries  ICMJE Netherlands
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04755127
Other Study ID Numbers  ICMJE ARCTIC01
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Maasstad Hospital
Study Sponsor  ICMJE Maasstad Hospital
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Radjesh Bisoendial, MD, PhD Maasstad ziekenhuis
PRS Account Maasstad Hospital
Verification Date February 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP