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Screening for Flare After b/tsDMARD Discontinuation in Rheumatoid Arthritis

Primary Purpose

Rheumatoid Arthritis

Status
Not yet recruiting
Phase
Not Applicable
Locations
Study Type
Interventional
Intervention
Discontinuation of biological/targeted synthetic disease modifying anti-rheumatic drug (b/tsDMARD)
Sponsored by
Medical University of Vienna
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for Rheumatoid Arthritis

Eligibility Criteria

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

Inclusion Criteria:

Patients with rheumatoid arthritis classified by the American College of Rheumatology/European League Against Rheumatism classification criteria

  • biological disease-modifying anti-rheumatic drug (bDMARD) or targeted synthetic disease-modifying anti-rheumatic drug (tsDMARD) treatment in monotherapy or in combination therapy with conventional synthetic disease-modifying anti-rheumatic drug (csDMARD) in a stable dosage and interval for ≥6 months. Previous extension of bDMARD or tsDMARD interval will also be accepted. bDMARDs and tsDMARDs will include all currently available originator and biosimilar compounds, with the exception of rituximab and its biosimilar compounds
  • No swollen joint by 28-joint count at baseline, and screening
  • C-reactive protein of ≤0.5mg/dL at baseline AND history of C-reactive protein >0,5mg/dl related to rheumatoid arthritis activity
  • Clinical disease activity index ≤10
  • Shared decision between patient and physician to attempt b/tsDMARD withdrawal
  • Willing and able to understand and follow the study procedures
  • Written informed consent
  • Female and male subjects aged ≥ 18 years

Exclusion Criteria:

  • History of or current extra-articular manifestation of rheumatoid arthritis, with exception of rheumatoid nodules
  • Systemic glucocorticoid treatment in the past 3 months
  • Intraarticular injection with glucocorticoids in the past 1 month
  • Joint replacement surgery other than total knee or hip arthroplasty or complete joint destruction
  • Power Doppler signal ≥2 in any assessed joint and/or tendon at screening or baseline

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Other

    Other

    Arm Label

    Assisted monitoring

    Clinical monitoring

    Arm Description

    In the Assisted monitoring arm, C-reactive protein and musculoskeletal ultrasound information will be made available to the clinical assessors who, at each time-point will use this information, along with information from the clinical examination, to identify patients experiencing recurrence of inflammation which will then be counted as subclinical flare according to predefined criteria.

    In the Clinical monitoring arm, the results of C-reactive protein and musculoskeletal ultrasound information will be recorded but will not be made available to the clinical assessor who at each time-point will make the decision on whether the patient is experiencing or has experienced a clinical flare according to predefined criteria based on information from the clinical examination.

    Outcomes

    Primary Outcome Measures

    Proportion of subjects without a clinical flare until week 24
    Proportion of subjects without a clinical flare

    Secondary Outcome Measures

    Proportion of subjects without a clinical flare
    Proportion of subjects without a clinical flare
    Time to clinical flare (days)
    Time to clinical flare (days)
    28 swollen joint count
    28 swollen joint count, scale 0 (best) - 28 (worse)
    28 tender joint count
    28 tender joint count, scale 0 (best) - 28 (worse)
    Proportion of subjects with a clinical flare in the assisted monitoring arm vs. clinical monitoring arm, the latter stratified according to b/tsDMARD reinitiation
    Proportion of subjects with a clinical flare in the assisted monitoring arm vs. clinical monitoring arm, the latter stratified according to b/tsDMARD reinitiation
    Proportion of patients in low disease activity or remission based on simplified disease activity index
    Proportion of patients in low disease activity or remission based on simplified disease activity index
    Proportion of patients in low disease activity or remission based on simplified disease activity index
    Proportion of patients in low disease activity or remission based on simplified disease activity index
    Patient's global assessment
    Patient's global assessment, scale 0 (best) - 100 (worst)
    Evaluator's global assessment
    Evaluator's global assessment, scale 0 (best) - 100 (worst)
    C-reactive protein
    C-reactive protein, scale 0 (best) - infinite (worst)
    Radiographic progression
    change in Sharp Van der Heijde score, scale 0 (best) - 488 (worse)
    Health Assessment Questionnaire Disability Index
    Health Assessment Questionnaire Disability Index, scale 0 (best) - 3.0 (worse)
    World Health Organization Quality of Life Questionnaire
    World Health Organization Quality of Life Questionnaire, scale 0 (worse) - 100 (best)
    Morning stiffness
    Morning joint stiffness, (minutes), scale 0 (best) - infinite (worst)
    Fatigue
    Fatigue, visual analogue scale, scale 0 (worse) - 100 (best)

    Full Information

    First Posted
    November 2, 2021
    Last Updated
    November 12, 2021
    Sponsor
    Medical University of Vienna
    Collaborators
    Medical University of Graz, Medical University Innsbruck, Hospital Hietzing, Krankenhaus Bruneck
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    1. Study Identification

    Unique Protocol Identification Number
    NCT05119452
    Brief Title
    Screening for Flare After b/tsDMARD Discontinuation in Rheumatoid Arthritis
    Official Title
    Screening for Flare After Discontinuation of Biological/Targeted Synthetic Disease Modifying Anti-rheumatic Drug (b/tsDMARD) in Rheumatoid Arthritis
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    November 2021
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    March 2022 (Anticipated)
    Primary Completion Date
    September 2024 (Anticipated)
    Study Completion Date
    September 2024 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Principal Investigator
    Name of the Sponsor
    Medical University of Vienna
    Collaborators
    Medical University of Graz, Medical University Innsbruck, Hospital Hietzing, Krankenhaus Bruneck

    4. Oversight

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

    5. Study Description

    Brief Summary
    To evaluate whether stringent follow-up consisting of combined laboratory and ultrasound surveillance is superior to clinical monitoring alone to maintain clinical remission in rheumatoid arthritis.
    Detailed Description
    Randomized, controlled, parallel-group, multi-centre study in which patients with rheumatoid arthritis treated with biological/targeted synthetic disease modifying antirheumatic drug (b/tsDMARD) in mono- or combination therapy with conventional synthetic disease modifying antirheumatic drug (csDMARD) in a stable dosage and interval for ≥6 months with low disease activity or remission will receive an power Doppler musculoskeletal ultrasound examination (PDUS) and monitoring of C-reactive protein (CRP) levels at baseline and several timepoints within a 24 month study period (primary endpoint) and within a 48 month long-term extension. At baseline, b/tsDMARD medication will be withdrawn in all patients, who will be randomized in a 1:1 ratio in an "Assisted monitoring" (arm A) or a "Clinical monitoring" (arm B) arm respectively. Further stratification for remission vs. low disease activity and mono- vs combination therapy will be implemented in the randomisation process. In arm A, CRP and PDUS information will be made available to the clinical assessors who, at each time-point will use this information along with that from clinical examination, to identify patients experiencing recurrence of inflammation which will then be counted as subclinical flare according to predefined criteria. In arm B the results of CRP and PDUS will be recorded but will not be made available to the clinical assessor who will have to identify clinical flares according to predefined criteria based on information from the clinical examination only.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Rheumatoid Arthritis

    7. Study Design

    Primary Purpose
    Other
    Study Phase
    Not Applicable
    Interventional Study Model
    Parallel Assignment
    Model Description
    At baseline, patients will be randomised in a 1:1 ratio in an "Assisted monitoring" (arm A) or a "Clinical monitoring" (arm B) arm respectively.
    Masking
    ParticipantInvestigator
    Masking Description
    After checking the inclusion- and exclusion criteria and after the patients´ consent the study investigator contacts the administrative office of the coordinating center. The online computerised randomisation algorithm "Randomizer for Clinical Trials by the Medical University of Vienna (MUW) will be used for randomisation for all centres.
    Allocation
    Randomized
    Enrollment
    85 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Assisted monitoring
    Arm Type
    Other
    Arm Description
    In the Assisted monitoring arm, C-reactive protein and musculoskeletal ultrasound information will be made available to the clinical assessors who, at each time-point will use this information, along with information from the clinical examination, to identify patients experiencing recurrence of inflammation which will then be counted as subclinical flare according to predefined criteria.
    Arm Title
    Clinical monitoring
    Arm Type
    Other
    Arm Description
    In the Clinical monitoring arm, the results of C-reactive protein and musculoskeletal ultrasound information will be recorded but will not be made available to the clinical assessor who at each time-point will make the decision on whether the patient is experiencing or has experienced a clinical flare according to predefined criteria based on information from the clinical examination.
    Intervention Type
    Other
    Intervention Name(s)
    Discontinuation of biological/targeted synthetic disease modifying anti-rheumatic drug (b/tsDMARD)
    Other Intervention Name(s)
    b/tsDMARD: Adalimumab, Infliximab, Golimumab, Certolizumab pegol, Tocilizumab, Sarilumab, Etanercept, Anakinra, Filgotinib, Updacitinib, Tofacitinib, Baricitinib
    Intervention Description
    The biological/targeted synthetic disease modifying anti-rheumatic drug will be discontinued in both arms at baseline
    Primary Outcome Measure Information:
    Title
    Proportion of subjects without a clinical flare until week 24
    Description
    Proportion of subjects without a clinical flare
    Time Frame
    week 24
    Secondary Outcome Measure Information:
    Title
    Proportion of subjects without a clinical flare
    Description
    Proportion of subjects without a clinical flare
    Time Frame
    week 48
    Title
    Time to clinical flare (days)
    Description
    Time to clinical flare (days)
    Time Frame
    study period
    Title
    28 swollen joint count
    Description
    28 swollen joint count, scale 0 (best) - 28 (worse)
    Time Frame
    week 24
    Title
    28 tender joint count
    Description
    28 tender joint count, scale 0 (best) - 28 (worse)
    Time Frame
    week 24
    Title
    Proportion of subjects with a clinical flare in the assisted monitoring arm vs. clinical monitoring arm, the latter stratified according to b/tsDMARD reinitiation
    Description
    Proportion of subjects with a clinical flare in the assisted monitoring arm vs. clinical monitoring arm, the latter stratified according to b/tsDMARD reinitiation
    Time Frame
    week 24
    Title
    Proportion of patients in low disease activity or remission based on simplified disease activity index
    Description
    Proportion of patients in low disease activity or remission based on simplified disease activity index
    Time Frame
    week 24
    Title
    Proportion of patients in low disease activity or remission based on simplified disease activity index
    Description
    Proportion of patients in low disease activity or remission based on simplified disease activity index
    Time Frame
    week 48
    Title
    Patient's global assessment
    Description
    Patient's global assessment, scale 0 (best) - 100 (worst)
    Time Frame
    week 24
    Title
    Evaluator's global assessment
    Description
    Evaluator's global assessment, scale 0 (best) - 100 (worst)
    Time Frame
    week 24
    Title
    C-reactive protein
    Description
    C-reactive protein, scale 0 (best) - infinite (worst)
    Time Frame
    week 24
    Title
    Radiographic progression
    Description
    change in Sharp Van der Heijde score, scale 0 (best) - 488 (worse)
    Time Frame
    at week 48 weeks from baseline
    Title
    Health Assessment Questionnaire Disability Index
    Description
    Health Assessment Questionnaire Disability Index, scale 0 (best) - 3.0 (worse)
    Time Frame
    week 24
    Title
    World Health Organization Quality of Life Questionnaire
    Description
    World Health Organization Quality of Life Questionnaire, scale 0 (worse) - 100 (best)
    Time Frame
    week 24
    Title
    Morning stiffness
    Description
    Morning joint stiffness, (minutes), scale 0 (best) - infinite (worst)
    Time Frame
    week 24
    Title
    Fatigue
    Description
    Fatigue, visual analogue scale, scale 0 (worse) - 100 (best)
    Time Frame
    week 24

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Patients with rheumatoid arthritis classified by the American College of Rheumatology/European League Against Rheumatism classification criteria biological disease-modifying anti-rheumatic drug (bDMARD) or targeted synthetic disease-modifying anti-rheumatic drug (tsDMARD) treatment in monotherapy or in combination therapy with conventional synthetic disease-modifying anti-rheumatic drug (csDMARD) in a stable dosage and interval for ≥6 months. Previous extension of bDMARD or tsDMARD interval will also be accepted. bDMARDs and tsDMARDs will include all currently available originator and biosimilar compounds, with the exception of rituximab and its biosimilar compounds No swollen joint by 28-joint count at baseline, and screening C-reactive protein of ≤0.5mg/dL at baseline AND history of C-reactive protein >0,5mg/dl related to rheumatoid arthritis activity Clinical disease activity index ≤10 Shared decision between patient and physician to attempt b/tsDMARD withdrawal Willing and able to understand and follow the study procedures Written informed consent Female and male subjects aged ≥ 18 years Exclusion Criteria: History of or current extra-articular manifestation of rheumatoid arthritis, with exception of rheumatoid nodules Systemic glucocorticoid treatment in the past 3 months Intraarticular injection with glucocorticoids in the past 1 month Joint replacement surgery other than total knee or hip arthroplasty or complete joint destruction Power Doppler signal ≥2 in any assessed joint and/or tendon at screening or baseline

    12. IPD Sharing Statement

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    Screening for Flare After b/tsDMARD Discontinuation in Rheumatoid Arthritis

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