Is Ultrasound Remission a Real Remission? Does Ultrasound Permit to Achieve and Maintain the Remission in Rheumatoid Arthritis Patients More Efficiently Than Clinical Scores? (REVECHO)

REVECHO Study (REmission Véritable en ECHOgraphie) Is Ultrasound Remission a Real Remission? Does Ultrasound Permit to Achieve and Maintain the Remission in Rheumatoid Arthritis Patients More Efficiently Than Clinical Scores?

Remission is nowadays an achievable objective for Rheumatoid Arthritis (RA) patients thanks to a large choice of therapies, early treatment and tight control (30% relapse).

Ultrasound (US) driven-therapy, complemented with a clinico-biological follow-up, may improve the prognosis of RA in remission by increasing the duration of sustained remission and by preventing radiographic structural progression.

The tested hypothesis is: The US coverage of RA allows to increase the duration of sustained clinical remission.

Study Overview

• Status: Unknown
• Conditions: Rheumatoid Arthritis; Remission
• Intervention / Treatment: Other: Usual care; Device: US power doppler; Other: ACR/EULAR criteria

Detailed Description

REVECHO is an international prospective multicentre simple blinded randomized study with a longitudinal follow-up of 18 months and a total study duration of 48 months. During the first visit, after having signed the consent form, Patients undergo at each visit, a clinical evaluation comprising an assessment of tender joint count (TJC), of swollen joint count (SJC), pain assessment, patient global assessment of the activity of disease, as well as a physician global assessment of the disease activity, an ultrasound examination of small and large joints by an independent physician blinded to the clinical data, and to the results of biological exams (blood sampling to assess CRP, complete blood count (CBS), and renal and hepatic functions). The clinical, biological and ultrasound assessments will be performed every 3 months.

Patients will be then randomly assigned to one of the 3 groups: 1) "Usual care group", 2) "Clinical (DAS28)-ultrasound follow-up group" (ultrasound-driven therapy) or 3) "DAS28-ACR/EULAR remission criteria group" (ACR/EULAR remission criteria-driven therapy), with a follow-up of 18 months.

Therapeutic decisions are taken by the Referring Rheumatologist. He/she will have DAS28 + US results in the group US follow-up or DAS28 + ACR/EULAR remission criteria results in the group ACR/EULAR follow-up. Therapeutic recommendations (therapeutic options, according to the randomization group, a threshold of activity will be decided by a scientific committee for increasing, stop or change therapy) will be given according to the group of randomization and based on the level of inflammation. The Referring Rheumatologist, will be free to follow or not the therapeutic advices.

In "Usual care" group, DAS28 and PDUS assessment will be performed at each time point, however, no suggestion neither DAS28 nor PDUS results will be given to the Referring Rheumatologist. The Referring Rheumatologist will be free to manage the patient as he/she thinks more appropriate.

Conventional radiography (hand and feet) will be performed at baseline and at M18 follow-up.

Centralized evaluation of radiographs will be performed by 2 independent readers, using SvH score. Radiographic progression will be defined by a change of SvH score between baseline and M18 >0.

PDUS examination will be performed every 3 months by an independent Physician in each centre, blinded to clinical, biological and radiographic data. Shoulders, elbows, wrists, MCP 1 to 5, PIP 1 to 5, knees, ankles (tibia-talar) and MTP 1 to 5 will be examined in B mode and in Power Doppler mode.

Each joint will be scored for synovitis according to the OMERACT definition and to the OMERACT scoring system (semi-quantitative score from 0 to 3 for grey scale, PD and for combined score).

Questionnaire (RAPID and HAQ) scores will be also evaluated every 3 months in each group.

• Study Type: Interventional
• Enrollment (Anticipated): 450
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Hauts DE Seine
    • Boulogne, Hauts DE Seine, France, 92104
      • Recruiting
      • Rheumatology Department, Ambroise Paré Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. RA patients (ACR 2010 criteria)
2. Disease duration ≤12 years
3. Patients of both genders above 18 years old
4. Remission according to DAS28 criteria (DAS28<2.6) since at least 3 months
5. Treated with DMARDS and/or biologics with stable posology since at least 3 months
6. Treated with corticosteroids ≤5 mg/day (oral, local intra-articular or perfusion) since at least 3 months
7. Affiliated to a regimen of health insurance (only for French sites)
8. Having signed a consent form
9. The patient is considered reliable, willing and capable of adhering to the protocol (for example, able to understand and complete diaries), visit schedule, and medication intake according to the judgment of the Investigator

Exclusion Criteria:

1. Pregnant women
2. Predictable difficulties of follow-up

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Usual care; Usual care and follow-up every 3 months	Other: Usual care; Clinical evaluation and follow-up according to the practice of the referring rheumatologist every 3 months
Experimental: US-driven therapy; Clinical evaluation according to DAS28 + US every 3 months	Device: US power doppler; Clinical evaluation according to DAS28 and US every 3 months. US examination is realized in B and Doppler power mode for each studied joint: Ankles, shoulders, elbows, wrists, MCP 1 to 5, PIP 1 to 5, knees and MTP 1 to 5.
Active Comparator: ACR/EULAR remission criteria-driven therapy; Clinical evaluation according to DAS28 + ACR/EULAR remission criteria every 3 months	Other: ACR/EULAR criteria; Evaluation based on clinical evaluation according to DAS28 and ACR/EULAR remission criteria every 3 months.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to loss of remission, as clinically defined by a DAS28 score ≥2.6	The DAS28 (Disease Activity Score for Rheumatoid Arthritis) score is calculated on the basis of swollen joint count (SJC) and tender joint count (TJC) out of 28 (shoulder, elbow, wrist, metacarpophalangeal (MCP) I-V, proximal interphalangeal (PIP) I-V, and knee) as follows: DAS28-CRP= 0.56 x √TJC + 0.28 x √SJC + 0.36 x Ln (CRP + 1) + 0.014 x GA + 0.96 As a result, the DAS28 index gives a value between 0 and 10, with: >5.1 indicating high disease activity; 3.2-5.1 indicating moderate disease activity; <3.2 indicating low disease activity; <2.6 complete remission	Up to 18 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of RA patients in clinical remission (DAS28 <2.6) at 18 months		18 months
Percentage of RA patients without radiographic structural progression	Percentage of RA patients without radiographic structural progression (delta-Van der Heijde modified Sharp score ≤0) at 18 months.	18 months
Evolution of the RAPID score and HAQ	Evolution of the RAPID (Routine Assessment of Patient Index Data score) and HAQ (Health Assessment Questionnaire).	18 months

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Collaborators: Pfizer
• Investigators: Principal Investigator: Maria-Antonietta D'Agostino, MD, PhD, Rheumatology Department, Ambroise Paré Hospital

Study record dates

Study Major Dates

• Study Start: October 1, 2014
• Primary Completion (Anticipated): October 1, 2018
• Study Completion (Anticipated): December 1, 2018

Study Registration Dates

• First Submitted: May 7, 2014
• First Submitted That Met QC Criteria: May 14, 2014
• First Posted (Estimate): May 16, 2014

Study Record Updates

• Last Update Posted (Actual): November 20, 2017
• Last Update Submitted That Met QC Criteria: November 17, 2017
• Last Verified: November 1, 2017

More Information

Terms related to this study

• Keywords: Rheumatoid Arthritis; DAS28,; Remission,; ACR/EULAR,; RAPID, Randomized study,; Longitudinal follow-up
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid
• Other Study ID Numbers: P130401