Ultrasound to Guide Treatment Decisions in Patients With Rheumatoid Arthritis According to a T2T Approach

NCT05717179 | Recruiting

• 1 other identifier: US-RA-T2T
• Study Type: interventional
• Target: 158
• Locations: 1 country
• Sites: 1

Brief Summary

Population Patients with a diagnosis of Rheumatoid Arthritis (RA), moderate or high clinical disease activity (CDAI\>10) despite conventional synthetic (cs)DMARD(s) or bs-ts-DMARDs therapy for ≥3 months, and a maximum of 2 swollen joints (out of 44 joints) Study design Randomised multicentre, parallel-arm clinical study Primary objective Non-inferiority of the experimental arm (i.e. clinical therapy together with ultrasound guided treatment decision) in comparison to the control arm (clinically guided decision) concerning the proportion of patients reaching low disease activity (CDAI ≤10) and a minimal clinical important improvement (MCII: improvement of ≥6 points if starting from moderate disease activity, any case starting from high disease activity and achieving low disease activity) or remission according to ACR/EULAR index-based remission criteria (CDAI ≤2.8/Boolean remission) at week 24. Intervention This is a randomised multicentre, national, parallel-arm clinical study. Patients with a diagnosis of RA, moderate or high clinical disease activity (CDAI\>10) despite conventional synthetic (cs)DMARD(s) or b-tsDMARDs therapy for ≥3 months, and a maximum of 2 swollen joints (out of 44 joints) will be included and randomized to one of the following two strategic arms:

• Total duration of the study: 72 months
• Active phase for each patient: 48 weeks (24 weeks for the interventional treatment strategy and 24 weeks for follow-up visit)
• Recruitment: 60 months

Conditions

Arthritis, Rheumatoid; Ultrasound; Treat to Target

Outcome Measures

Primary Outcomes (1)

• Non-inferiority of ultrasound-based decision strategy compared to clinically-based strategy.

  Non-inferiority of the experimental arm (i.e. clinical plus ultrasound-guided treatment decision) in comparison to the control arm (clinically-guided decision) concerning the proportion of patients reaching low disease activity (CDAI ≤10) and a minimal clinical important improvement (MCII: improvement of ≥6 points if starting from moderate disease activity, any case achieving low disease activity who started from high disease activity) \[19\] or remission according to ACR/EULAR index-based remission criteria (CDAI ≤2.8/Boolean remission) at week 24.

  24 weeks

Secondary Outcomes (24)

• Comparison of the proportion of patients in low disease activity and MCII or remission according to ACR/EULAR index-based remission criteria at week 12 and 48

  12 and 48 weeks

• Comparison of the proportion of patients in remission according to ACR/EULAR index-based remission criteria (CDAI ≤2.8/Boolean remission, respectively) at week 12, 24 and 48

  12, 24 and 48 weeks

• Comparison of the proportion of patients in remission according to DAS-28 (DAS-28 ≤2.6) or SDAI (≤3.3) at week 12, 24 and 48

  12, 24 and 48 weeks

• Comparison of value of tender joints count at weeks 12, 24 and 48

  12, 24 and 48 weeks

• Comparison of value of swollen joints counts at weeks 12, 24 and 48

  12, 24 and 48 weeks

Study Arms (2)

Conventional decision strategy

NO INTERVENTION

All patients receive a new course of b-ts-DMARDs, with or without concomitant cDMARD. If a CDAI ≤10 is not achieved after 12 weeks, patients are switched to a bDMARD or tsDMARD. The decision on which b/tsDMARD to use at week 12 is at the discretion of the investigator.

Clinical plus ultrasound-based decision strategy

EXPERIMENTAL

All patients in this group will be evaluated by ultrasound at 44 joints. In case of clinically-verified plus ultrasound verified inflammation, patients will receive a new b-ts-DMARD while continuing or not background csDMARD(s) therapy. If a CDAI ≤10 is not achieved after 12 weeks, patients are again evaluated by ultrasound at 44 joints. In case clinically-verified plus ultrasound-verified inflammation is present, patients are switched to a bDMARD or tsDMARD. The decision on which b/tsDMARD to use is at the discretion of the investigator. In case clinically-verified plus ultrasound-verified inflammation is absent, patients receive step-up pain therapy while background treatment will be continued.

Diagnostic Test: Ultrasound

Interventions

Ultrasound DIAGNOSTIC_TEST

At baseline and at weeks 12, 24 and 48, patients will undergo an ultrasound examination of 44 joints by one investigator, who is blinded to the strategic arm and all clinical data. The following joints will be assessed: bilateral wrists (distal radio-ulnar joint, radio-carpal, mid-carpal recesses), 1st - 5th MCP, 1st - 5th PIP, elbows, glenohumeral, acromioclavicular, sternoclavicular, knees, ankles and 1st - 5th MTP. At wrists, MCP and PIP joints, palmar and dorsal sites including synovial recess, extensor and flexor tendons will be investigated whereas at feet the dorsal site (plus the lateral aspects of MTP5) including synovial recess and extensor tendons will be evaluated. Further, we will assess the following: at elbows the dorsal and anterior recess, at shoulders the dorsal recess, at knees the suprapatellar as well as the medial and lateral femoro-tibial recess and at ankles the anterior, lateral and medial recess of the tibiotalar joint.

Clinical plus ultrasound-based decision strategy

Eligibility Criteria

• Age: 18 Years - 84 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Classification of RA according to the ACR-EULAR 2010 criteria
• Age of the patients: 18 to 84 years
• Patients with moderate or high disease activity according to CDAI (\>10)
• Maximum of 2 clinically swollen joints out of a 44-joint count
• Current stable treatment with a single csDMARD or bDMARD or tsDMARD for at least 3 months
• No glucocorticoid therapy or stable glucocorticoid dose for at least 4 weeks and at a maximum dose of 5 mg/day prednisone equivalent.
• No corticosteroid intraarticular injection within 4 weeks
• Stable or absent dose of NSAIDs for at least 1 week
• Patients able and willing to give written informed consent and compliant with the requirements of the study protocol

You may not qualify if:

• Complete (clinically evident) destruction of any joint to be investigated by ultrasound as judged by the physician
• Current RA-related vasculitis or other active systemic (i.e. extraarticular) RA-manifestation except for rheumatoid nodules, which in the opinion of the investigator would expose the study subject to a high risk of morbidity or mortality
• Initial arthritis manifestations before the age of 18 years
• Planned surgery within the study period for any of the joints investigated either clinically or by sonography
• Current severe medical illness requiring hospitalization
• Active infection or active malignancy at screening \<5 years
• Any contraindication to b/ts DMARDs according to the "Summary of Product Characteristics"
• Pregnancy or lactation

Sponsors & Collaborators

• Italian Society for Rheumatology: lead

Study Sites (1)

Azienda Sanitaria dell'Alto Adige

Bruneck, Bolzano, 39031, Italy

RECRUITING

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

Ultrasonography

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Diagnostic Imaging; Diagnostic Techniques and Procedures; Diagnosis

Central Study Contacts

Christian Dejaco, MD, PhD

CONTACT

+390474581862; Christian.Dejaco@sabes.it

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 15, 2022
• First Posted: February 8, 2023
• Study Start: February 22, 2023
• Primary Completion (Estimated): August 1, 2028
• Study Completion (Estimated): February 1, 2029
• Last Updated: May 14, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)