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Ultrasound to Guide Treatment Decisions in Patients With Rheumatoid Arthritis According to a T2T Approach (US-RA-T2T)

Primary Purpose

Arthritis, Rheumatoid, Ultrasound, Treat to Target

Status
Recruiting
Phase
Not Applicable
Locations
Italy
Study Type
Interventional
Intervention
Ultrasound
Sponsored by
Italian Society for Rheumatology
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Arthritis, Rheumatoid

Eligibility Criteria

18 Years - 84 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: 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 a combination thereof 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 Exclusion Criteria: Previous or current treatment with any b/ts DMARD 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

Sites / Locations

  • Azienda Sanitaria dell'Alto AdigeRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

No Intervention

Experimental

Arm Label

Clinical decision strategy

Clinical plus ultrasound-based decision strategy

Arm Description

All patients receive a TNF-alpha blocker while continuing background csDMARD(s) therapy. 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.

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 TNF-alpha blocker while continuing 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 csDMARD(s) will be continued.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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
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
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
Comparison of value of tender joints count at weeks 12, 24 and 48
Comparison of value of swollen joints counts at weeks 12, 24 and 48
Comparison of value of VAS (Visual Analogue Scale) pain at weeks 12, 24 and 48
Range: 0, better outcome - 100, worse outcome
Comparison of value of VAS (Visual Analogue Scale) Patient Global Assessment of Disease Activity at weeks 12, 24 and 48
Range: 0, better outcome - 100, worse outcome
Comparison of value of VAS (Visual Analogue Scale) Physician Global Assessment of Disease Activity at weeks 12, 24 and 48
Range: 0, better outcome - 100, worse outcome
Comparison of value of erythrocyte sedimentation rate (ESR) at weeks 12, 24 and 48
Comparison of value of C reactive protein (CRP) at weeks 12, 24 and 48
Comparison of Health assessment questionnaire (HAQ) score at week 24 and 48
Range: 0, better outcome - 3, worse outcome
Comparison of Rheumatoid Arthritis Impact of Disease (RAID) score at week 24 and 48
Range: 0, better outcome - 10, worse outcome
Comparison of Fatigue Assessment Scale (FAS) score at week 24 and 48
Range: 10, better outcome - 50, worse outcome
Comparison of EuroQol-5 dimensions (EQ5D) score at week 24 and 48
Comparison of the trend of VAS (Visual Analogue Scale) pain across all study visits
Absolute and relative change of parameter with respect to the baseline and between different visits
Comparison of the trend of VAS (Visual Analogue Scale) Patient Global Assessment of Disease Activity across all study visits
Absolute and relative change of parameter with respect to the baseline and between different visits
Comparison of the trend of Health assessment questionnaire (HAQ) score across all study visits
Absolute and relative change of score with respect to the baseline and between different visits
Comparison of the trend of Rheumatoid Arthritis Impact of Disease (RAID) score across all study visits
Absolute and relative change of score with respect to the baseline and between different visits
Comparison of the trend of Fatigue Assessment Scale (FAS) score across all study visits
Absolute and relative change of score with respect to the baseline and between different visits
Comparison of the trend of EuroQol-5 dimensions (EQ5D) score across all study visits
Absolute and relative change of score with respect to the baseline and between different visits
Comparison of the differences in the Sharp van der Heijde Score from baseline to week 48
Range: 0, better outcome - 448, worse outcome
Comparison of patients achieving a PD score of ≤1 (44-joint count) at weeks 12, 24 and 48
Comparison of direct medical costs of treatment arms from baseline to week 24 and 48
Measurement: Incremental cost-effectiveness ratio (ICER)
Analysis regarding predictors of low disease activity or remission at 12, 24 and 48 weeks in patients treated with ≥1bDMARD as compared to those who receive pain therapy
Investigated predictors: baseline erythrocyte sedimentation rate, baseline C reactive protein, baseline ultrasound score (EULAR-OMERACT combined score)

Full Information

First Posted
December 15, 2022
Last Updated
October 6, 2023
Sponsor
Italian Society for Rheumatology
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1. Study Identification

Unique Protocol Identification Number
NCT05717179
Brief Title
Ultrasound to Guide Treatment Decisions in Patients With Rheumatoid Arthritis According to a T2T Approach
Acronym
US-RA-T2T
Official Title
Ultrasound to Guide Treatment Decisions in Patients With Rheumatoid Arthritis According to a T2T Approach
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
February 22, 2023 (Actual)
Primary Completion Date
February 2026 (Anticipated)
Study Completion Date
August 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Italian Society for Rheumatology

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

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) therapy for ≥3 months, naïve to biological (b) and targeted synthetic (ts)DMARDs therapy 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) therapy for ≥3 months, naïve to biological (b) and targeted synthetic (ts)DMARDs therapy and a maximum of 2 swollen joints (out of 44 joints) will be included and randomized to one of the following two strategic arms: Clinical decision strategy: All patients receive a TNF-alpha blocker while continuing background csDMARD(s) therapy. 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. 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 TNF-alpha blocker while continuing 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 csDMARD(s) will be continued. Sample size 110 patients Time plan Total duration of the study: 42 months Active phase for each patient: 48 weeks (24 weeks for the interventional treatment strategy and 24 weeks for follow-up visit) Recruitment: 30 months

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Arthritis, Rheumatoid, Ultrasound, Treat to Target

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
110 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Clinical decision strategy
Arm Type
No Intervention
Arm Description
All patients receive a TNF-alpha blocker while continuing background csDMARD(s) therapy. 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.
Arm Title
Clinical plus ultrasound-based decision strategy
Arm Type
Experimental
Arm Description
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 TNF-alpha blocker while continuing 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 csDMARD(s) will be continued.
Intervention Type
Diagnostic Test
Intervention Name(s)
Ultrasound
Intervention Description
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.
Primary Outcome Measure Information:
Title
Non-inferiority of ultrasound-based decision strategy compared to clinically-based strategy.
Description
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 weeks
Secondary Outcome Measure Information:
Title
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 weeks
Title
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 weeks
Title
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 weeks
Title
Comparison of value of tender joints count at weeks 12, 24 and 48
Time Frame
12, 24 and 48 weeks
Title
Comparison of value of swollen joints counts at weeks 12, 24 and 48
Time Frame
12, 24 and 48 weeks
Title
Comparison of value of VAS (Visual Analogue Scale) pain at weeks 12, 24 and 48
Description
Range: 0, better outcome - 100, worse outcome
Time Frame
12, 24 and 48 weeks
Title
Comparison of value of VAS (Visual Analogue Scale) Patient Global Assessment of Disease Activity at weeks 12, 24 and 48
Description
Range: 0, better outcome - 100, worse outcome
Time Frame
12, 24 and 48 weeks
Title
Comparison of value of VAS (Visual Analogue Scale) Physician Global Assessment of Disease Activity at weeks 12, 24 and 48
Description
Range: 0, better outcome - 100, worse outcome
Time Frame
12, 24 and 48 weeks
Title
Comparison of value of erythrocyte sedimentation rate (ESR) at weeks 12, 24 and 48
Time Frame
12, 24 and 48 weeks
Title
Comparison of value of C reactive protein (CRP) at weeks 12, 24 and 48
Time Frame
12, 24 and 48 weeks
Title
Comparison of Health assessment questionnaire (HAQ) score at week 24 and 48
Description
Range: 0, better outcome - 3, worse outcome
Time Frame
24 and 48 weeks
Title
Comparison of Rheumatoid Arthritis Impact of Disease (RAID) score at week 24 and 48
Description
Range: 0, better outcome - 10, worse outcome
Time Frame
24 and 48 weeks
Title
Comparison of Fatigue Assessment Scale (FAS) score at week 24 and 48
Description
Range: 10, better outcome - 50, worse outcome
Time Frame
24 and 48 weeks
Title
Comparison of EuroQol-5 dimensions (EQ5D) score at week 24 and 48
Time Frame
24 and 48 weeks
Title
Comparison of the trend of VAS (Visual Analogue Scale) pain across all study visits
Description
Absolute and relative change of parameter with respect to the baseline and between different visits
Time Frame
48 weeks
Title
Comparison of the trend of VAS (Visual Analogue Scale) Patient Global Assessment of Disease Activity across all study visits
Description
Absolute and relative change of parameter with respect to the baseline and between different visits
Time Frame
48 weeks
Title
Comparison of the trend of Health assessment questionnaire (HAQ) score across all study visits
Description
Absolute and relative change of score with respect to the baseline and between different visits
Time Frame
48 weeks
Title
Comparison of the trend of Rheumatoid Arthritis Impact of Disease (RAID) score across all study visits
Description
Absolute and relative change of score with respect to the baseline and between different visits
Time Frame
48 weeks
Title
Comparison of the trend of Fatigue Assessment Scale (FAS) score across all study visits
Description
Absolute and relative change of score with respect to the baseline and between different visits
Time Frame
48 weeks
Title
Comparison of the trend of EuroQol-5 dimensions (EQ5D) score across all study visits
Description
Absolute and relative change of score with respect to the baseline and between different visits
Time Frame
48 weeks
Title
Comparison of the differences in the Sharp van der Heijde Score from baseline to week 48
Description
Range: 0, better outcome - 448, worse outcome
Time Frame
48 weeks
Title
Comparison of patients achieving a PD score of ≤1 (44-joint count) at weeks 12, 24 and 48
Time Frame
12, 24 and 48 weeks
Title
Comparison of direct medical costs of treatment arms from baseline to week 24 and 48
Description
Measurement: Incremental cost-effectiveness ratio (ICER)
Time Frame
24 and 48 weeks
Title
Analysis regarding predictors of low disease activity or remission at 12, 24 and 48 weeks in patients treated with ≥1bDMARD as compared to those who receive pain therapy
Description
Investigated predictors: baseline erythrocyte sedimentation rate, baseline C reactive protein, baseline ultrasound score (EULAR-OMERACT combined score)
Time Frame
12, 24 and 48 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
84 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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 a combination thereof 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 Exclusion Criteria: Previous or current treatment with any b/ts DMARD 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Christian Dejaco, MD, PhD
Phone
+390474581862
Email
Christian.Dejaco@sabes.it
Facility Information:
Facility Name
Azienda Sanitaria dell'Alto Adige
City
Brunico
State/Province
Bolzano
ZIP/Postal Code
39031
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Christian Dejaco, MD, PhD
Phone
+390474581862
Email
Christian.Dejaco@sabes.it

12. IPD Sharing Statement

Plan to Share IPD
No

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

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