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An MRI-guided Treatment Strategy to Prevent Disease Progression in Patients With Rheumatoid Arthritis (IMAGINE-RA)

Does an MRI-guided Treatment Strategy Reduce Disease Activity and Progression in Patients With Rheumatoid Arthritis (RA): a Randomised Controlled Trial

The purpose of this study is to examine whether an magnetic resonance imaging (MRI) -guided treatment strategy based on a predefined treatment algorithm can prevent progression of erosive joint damage, increase remission rate and improve functional level in the short and long term in patients with rheumatoid arthritis (RA).

Aperçu de l'étude

Description détaillée

Rheumatoid arthritis (RA) is a chronic inflammatory joint disease. Patients typically experience pain, functional impairment and reduced quality of life, and are at risk of developing progressive joint damage. The disease primarily affects the small joints of the hands and feet. The current treatment strategy involves early and intensive treatment with close clinical follow up, which attempts to control the disease and avoid inflammation and thereby prevent pain, improve functional level and avoid joint damage. It is therefore important for optimal treatment of RA patients that methods used for diagnosis, disease monitoring and prognostication are highly sensitive. Erosive joint damage occurs early in the disease. Joint deformity is irreversible and causes serious functional impairment. Early and intensive treatment with close monitoring of the inflammation can slow the destructive disease and prevent function loss. However, it has been demonstrated that patients who are shown by conventional clinical and biochemical examination to have low disease activity or to be in remission can still have progressive joint damage. This demonstrates that current clinical/biochemical methods used in daily clinical practice are not sufficiently sensitive and other methods are required for the monitoring of disease activity and prognostication.

The presence of erosions (shown by X-ray examination) as well as anti-cyclic citrullinated peptide (anti-CCP) antibodies and bone marrow oedema (osteitis) on magnetic resonance imaging (MRI), are all independent predictors of subsequent radiographic progression. Bone marrow oedema has been shown to be the strongest independent predictor in early RA and MRI therefore has significant prognostic value.

It is therefore possible that supplementing conventional clinical and biochemical examinations of RA patients with MRI, and intensifying treatment where bone marrow oedema is present, will help reduce disease activity, avoid progressive joint damage and prevent function loss.

The current study is therefore based on the following hypothesis:

By supplementing conventional clinical and biochemical examination of RA patients with low disease activity/in remission with MRI and intensifying treatment in the case of sub-clinical inflammation as measured by the presence of bone marrow oedema, it is possible to prevent radiographic erosive progression, improve functional level and enable more patients to achieve clinical remission.

Type d'étude

Interventionnel

Inscription (Réel)

200

Phase

  • N'est pas applicable

Contacts et emplacements

Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.

Lieux d'étude

      • Aarhus, Danemark, 8600
        • Dep. of Rheumatology Aarhus Hospital
      • Copenhagen, Danemark, 2000
        • Dep. of Rheumatology Frederiksberg Hospital
      • Copenhagen, Danemark, 2600
        • Dep. of Rheumatology Glostrup Hospital
      • Copenhagen, Danemark, 2900
        • Dep. of Rheumatology Gentofte Hospital
      • Graasten, Danemark, 6300
        • Dep. of Rheumatology King Christian X´Hospital for Rheumatic Diseases
      • Hjørring, Danemark, DK-9800
        • Department of Rheumatology University Hospital Vendsyssel
      • Odense, Danemark, 5000
        • Dep. of rheumatology Odense Hospital
      • Silkeborg, Danemark, 8600
        • Dep. of Rheumatology Silkeborg Hospital
      • Slagelse, Danemark, 4200
        • Dep. of Rheumatology Slagelse Hospital

Critères de participation

Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.

Critère d'éligibilité

Âges éligibles pour étudier

18 ans et plus (Adulte, Adulte plus âgé)

Accepte les volontaires sains

Non

Sexes éligibles pour l'étude

Tout

La description

Inclusion Criteria:

  • Age > 18 years
  • RA according to ACR (American College of Rheumatology)/EULAR (European League Against Rheumatism) 2010 criteria.
  • Anti-CCP positivity
  • Erosions on conventional X-ray of hands, wrists and/or feet
  • No clinically swollen joints
  • DAS28 (4 variable, CRP) < 3.2
  • DMARD monotherapy treatment OR combination treatment, in the form of 2- or 3-drug therapy. If the patient is undergoing 3-drug therapy, at least one of the preparations must be administered at less than the "maximum inclusion dose"*
  • Unchanged anti-rheumatic treatment in the previous 6 weeks or more
  • No previous treatment with biological medication
  • No contra-indications for TNF-alpha-inhibiting treatment
  • No contra-indications for MRI
  • s-creatinine within normal range
  • Ability and willingness to give written and oral informed consent and fulfil the requirements of the study programme with reference to the protocol

    • Maximum "inclusion dose" is defined as: MTX 25 mg/week (or maximum tolerated dose if 25 mg/week is not tolerated), SSZ 2g/day (or maximum tolerated dose if 2 g/day is not tolerated) and HCQ 200 mg/day (or maximum tolerated dose if 200 mg/day is not tolerated)

Exclusion Criteria:

  • Previous or current biological treatment
  • Known intolerance to methotrexate treatment which means that the patient is not able to tolerate a minimum of MTX 7.5 mg (minimum dose).
  • DMARD 3-drug therapy at maximum tolerated/maximum "inclusion dose"*
  • I.m, intra-articular or i.v glucocorticoid administration ≤ 6 weeks prior to inclusion
  • Oral glucocorticoid administration > 5 mg/day
  • Changes in oral glucocorticoid dose < 3 months prior to inclusion
  • Myocrisin treatment
  • Affected liver enzymes > 2 x the upper limit of normal at the time of screening
  • Current and/or imminent wish to become pregnant
  • Contra-indications for TNF-alpha-inhibiting treatment
  • Contra-indications for MRI
  • Known alcohol/drug abuse
  • Inability to give informed consent
  • Inability to cooperate with the study programme due to physical or mental reasons

Plan d'étude

Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.

Comment l'étude est-elle conçue ?

Détails de conception

  • Objectif principal: Traitement
  • Répartition: Randomisé
  • Modèle interventionnel: Affectation parallèle
  • Masquage: Seul

Armes et Interventions

Groupe de participants / Bras
Intervention / Traitement
Comparateur actif: Conventional biochemical and clinical examinations
Biochemical and clinical examinations
Treatment algorithm based on conventional biochemical and clinical examinations. Assessed month 0, 4, 8, 12, 16, 20, 24 with treatment intensification after predefined treatment algorithm in the case of "unsatisfactory inflammatory activity", which is defined as the presence of at least one clinically swollen joint and DAS28>3.2
Expérimental: Conventional biochemical and clinical examinations and MRI.
Biochemical and clinical examinations and MRI.
Treatment algorithm based on conventional biochemical/clinical examinations AND MRI of unilateral 2nd to 5th MCP joints and wrist on dominant side. Assessed month 0, 4, 8, 12, 16, 20, 24 with treatment intensification after predefined treatment algorithm in the case of "unsatisfactory inflammatory activity", which is defined as the presence of at least one physically swollen joint and DAS28>3.2 AND/OR MRI-detected bone marrow oedema score > 0 (RAMRIS-score)

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats
Délai
DAS28 remission (<2.6)
Délai: 24 month
24 month
No radiographic progression (assessed by the Sharp/vdHeijde method).
Délai: 24 month
24 month

Mesures de résultats secondaires

Mesure des résultats
Description de la mesure
Délai
No radiographic progression (Sharp/vdHeijde score).
Délai: 24 month
No radiographic progression (Sharp/vdHeijde score) from 0-12 and 12-24 months and change in Sharp/vdHeijde score from 0-12, 0-24 and 12-24 months.
24 month
No MRI erosion (RAMRIS) score
Délai: 24 month
No progression in MRI erosion (RAMRIS) score from 0-12 and 12-24 months and change in MRI erosion (RAMRIS) score from 0-12, 0-24 and 12-24 months.
24 month
MRI synovitis (RAMRIS) score
Délai: 24 months
MRI synovitis (RAMRIS) score at 12 and 24 months
24 months
MRI bone marrow oedema (RAMRIS) score
Délai: 24 months
MRI bone marrow oedema (RAMRIS) score at 12 and 24 months
24 months
HAQ score
Délai: 24 month
Changes in HAQ score from 0-12 and 0-24 months
24 month
SF-36 score
Délai: 24 month
Changes in SF-36 score from 0-12 and 0-24 months
24 month
EQ-5D score
Délai: 24 month
Changes in EQ-5D score from 0-12 and 0-24 months
24 month
ACR/EULAR 2011 remission
Délai: 24 month
ACR/EULAR 2011 remission at 12 and 24 months
24 month
DAS28
Délai: 24 month
DAS28 at 12 and 24 month
24 month
DAS28 remission (<2.6) at 12 months
Délai: 24 months
24 months
biomarker analyses
Délai: 24 month
24 month

Autres mesures de résultats

Mesure des résultats
Description de la mesure
Délai
Dynamic MRI
Délai: 24 month
Dynamic MRI variable (including initial rate of enhancement (IRE) and maximum enhancement (ME)).
24 month

Collaborateurs et enquêteurs

C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.

Les enquêteurs

  • Chercheur principal: Kim Hørslev-Petersen, Professor, King Christian X´Hospital for Rheumatic Diseases
  • Directeur d'études: Signe Møller-Bisgaard, MD, Dep. of Rheumatology, Rigshospitalet, Glostrup
  • Chaise d'étude: Mikkel Østergaard, Professor, Dep. of Rheumatology, Rigshospitalet, Glostrup
  • Chaise d'étude: Bo Ejbjerg, MD, PhD, Dep. of Rheumatology Slagelse Hospital
  • Chaise d'étude: Merete Hetland, MD, PhD, DMSci, Dep. of Rheumatology, Rigshospitalet, Glostrup

Publications et liens utiles

La personne responsable de la saisie des informations sur l'étude fournit volontairement ces publications. Il peut s'agir de tout ce qui concerne l'étude.

Publications générales

Dates d'enregistrement des études

Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.

Dates principales de l'étude

Début de l'étude (Réel)

1 mars 2012

Achèvement primaire (Réel)

1 mai 2017

Achèvement de l'étude (Réel)

1 mai 2017

Dates d'inscription aux études

Première soumission

5 juillet 2012

Première soumission répondant aux critères de contrôle qualité

31 juillet 2012

Première publication (Estimation)

2 août 2012

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Réel)

23 juin 2017

Dernière mise à jour soumise répondant aux critères de contrôle qualité

22 juin 2017

Dernière vérification

1 juin 2017

Plus d'information

Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .

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