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

NCT ID: NCT05717179

Last Updated: 2025-05-14

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 158 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-02-22
• Study Completion Date: 2029-02-28

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:

1. Clinical decision strategy: 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.

2. Clinical plus ultrasound-based decision strategy. 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.

Sample size

158 patients

Time plan

• 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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Conventional decision strategy

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.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Clinical plus ultrasound-based decision strategy

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.

Group Type: EXPERIMENTAL

Ultrasound

Intervention Type: 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.

Interventions

Ultrasound

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.

Intervention Type: DIAGNOSTIC_TEST

Eligibility Criteria

Inclusion Criteria

1. Classification of RA according to the ACR-EULAR 2010 criteria

2. Age of the patients: 18 to 84 years

3. Patients with moderate or high disease activity according to CDAI (>10)

4. Maximum of 2 clinically swollen joints out of a 44-joint count

5. Current stable treatment with a single csDMARD or bDMARD or tsDMARD for at least 3 months

6. No glucocorticoid therapy or stable glucocorticoid dose for at least 4 weeks and at a maximum dose of 5 mg/day prednisone equivalent.

7. No corticosteroid intraarticular injection within 4 weeks

8. Stable or absent dose of NSAIDs for at least 1 week

9. Patients able and willing to give written informed consent and compliant with the requirements of the study protocol

Exclusion Criteria

1. Complete (clinically evident) destruction of any joint to be investigated by ultrasound as judged by the physician

2. 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

3. Initial arthritis manifestations before the age of 18 years

4. Planned surgery within the study period for any of the joints investigated either clinically or by sonography

5. Current severe medical illness requiring hospitalization

6. Active infection or active malignancy at screening <5 years

7. Any contraindication to b/ts DMARDs according to the "Summary of Product Characteristics"

8. Pregnancy or lactation

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 84 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Italian Society for Rheumatology

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Azienda Sanitaria dell'Alto Adige

Bruneck, Bolzano, Italy

Site Status: RECRUITING

Countries

Italy

Central Contacts

Christian Dejaco, MD, PhD

Role: CONTACT

Christian.Dejaco@sabes.it

+390474581862

Facility Contacts

Christian Dejaco, MD, PhD

Role: primary

Christian.Dejaco@sabes.it

+390474581862

Other Identifiers

US-RA-T2T

Identifier Type: -

Identifier Source: org_study_id