Ultrasound to Guide Treatment Decisions in Patients With Rheumatoid Arthritis According to a T2T Approach
Trial statusRecruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexAll
Age18-84
SponsorItalian Society for Rheumatology
About this trial
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
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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
Disqualifiers
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
Trial design
Design model
Parallel
Treatments tested in this trial
Ultrasound
Diagnostic testAt 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.
Treatment groups
158 Participants
are divided into 2 treatment groupsGroup A: Conventional decision strategyNo intervention 0 interventions
Group B: Clinical plus ultrasound-based decision strategyExperimental treatment 1 intervention
Trial outcomes
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.
Time frame
24 weeksSecondary outcomes
1
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
Time frame
12 and 48 weeks2
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
Time frame
12, 24 and 48 weeks3
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
Time frame
12, 24 and 48 weeks4
Comparison of value of tender joints count at weeks 12, 24 and 48
Time frame
12, 24 and 48 weeksSponsors and contacts
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Source ClinicalTrials.gov