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Giant Cell Arteritis: Comparison Between Two Standardized Corticosteroids Tapering (CORTODOSE)

Primary Purpose

Giant Cell Arteritis

Status
Not yet recruiting
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
Corticosteroids for Systemic Use
Sponsored by
University Hospital, Caen
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Giant Cell Arteritis focused on measuring Giant Cell Arteritis, Horton disease, Corticosteroids treatment, Prednisone, Relapse, Side effect, Cumulative doses

Eligibility Criteria

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

Inclusion Criteria:

  • Age ≥ 50 years
  • Patient with temporal arteritis giant cell match 2 of the 4 criteria of the American College of Rheumatology (ACR) that given :

    • a temporal artery biopsy compatible with a diagnosis of CAG or
    • an abdominal thoracic aortitis diagnosed by Angio CT, MR angiography or PET scanner or
    • Echo Doppler compatible with a diagnosis of CAG
  • Oral corticosteroid treatment started up to 14 days, the initial dose is less or equal to 1 mg / Kg
  • Patient wo has given its written consent Patient affiliated with a social security

Exclusion Criteria:

Subjects checking one of the criteria for non-inclusion may be eligible to participate in the research. These criteria may include:

  • Early treatment of CAG disease with a dose> 1 mg / kg whatever the duration
  • Corticosteroids already started over 14 days
  • Giant arteritis cell on relapse
  • dementia syndrome
  • No compliant patient
  • Patients who live more than 150 km from the investigation center
  • Person under judicial protection, guardianship
  • Hypersensitivity to prednisone or any of its excipients
  • Infection requiring an systemic treatment
  • Evolutive viroses (Hepatitis, Herpes, varicella-zoster virus)
  • Immunization with live vaccines / mitigated during the 8 weeks preceding inclusion
  • Pregnancy, breastfeeding women or women of childbearing potential not using contraception

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Active Comparator

    Arm Label

    Short tapering corticosteroids

    Long tapering corticosteroids

    Arm Description

    Corticosteroid taper over 28 weeks

    Corticosteroid taper over 52 weeks

    Outcomes

    Primary Outcome Measures

    Patient in complete remission over a follow up of 52 weeks, without relapse

    Secondary Outcome Measures

    First relapses rate at S28 and S52
    Second relapses rate at S28 and S52
    Delay between first and second relapses
    Cumulative and the average dose of prednisone used
    Number of patient with corticosteroids dependence at week 52
    Safety according CTCAE v5.0

    Full Information

    First Posted
    July 5, 2019
    Last Updated
    October 13, 2020
    Sponsor
    University Hospital, Caen
    Collaborators
    University Hospital, Lille, Amiens University Hospital, University Hospital, Rouen, University Hospital, Limoges, Central Hospital Saint Quentin, Central Hospital, Valenciennes, Central Hospital, Lisieux
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    1. Study Identification

    Unique Protocol Identification Number
    NCT04012905
    Brief Title
    Giant Cell Arteritis: Comparison Between Two Standardized Corticosteroids Tapering
    Acronym
    CORTODOSE
    Official Title
    A Randomized, Controled, Open Label Trial: Comparison Between Two Standardized Corticosteroids Tapering, Respectively Short (North American) and Long (European), in Giant Cell Arteritis
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    October 2020
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    November 5, 2020 (Anticipated)
    Primary Completion Date
    November 2023 (Anticipated)
    Study Completion Date
    January 2027 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    University Hospital, Caen
    Collaborators
    University Hospital, Lille, Amiens University Hospital, University Hospital, Rouen, University Hospital, Limoges, Central Hospital Saint Quentin, Central Hospital, Valenciennes, Central Hospital, Lisieux

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No
    Product Manufactured in and Exported from the U.S.
    No
    Data Monitoring Committee
    Yes

    5. Study Description

    Brief Summary
    Corticosteroid therapy has always been the standard treatment for giant cell arteritis (GCA), with very good initial clinical efficacy but a high relapse rate when it declines. The target population of this condition, often elderly, is particularly exposed to the numerous undesirable effects of corticosteroid therapy, and this especially as its duration lengthens with the re-increases of doses according to relapses: metabolic complications, osteo-muscular , infectious or neuropsychiatric. Investigators propose to compare prospectively the results of a "conventional" corticosteroid regimen as recommended by European societies, to those of a "lighter and / or shorter" scheme, inspired by recent North American trials. , including the largest prospective global study in the field. Investigators hypothesize non-inferiority of the lightened regimen for relapse rate without relapse at S52, but with a decrease in treatment-related adverse events whose cumulative doses should be lower. Investigators therefore plan to include prospectively over 3 years 150 patients, 75 for each of the two arms, with a newly diagnosed ACG. A randomization of the treatment arm will be performed and a predefined pattern of cortisone adapted to body weight will be given to the patient. Relapse rates, maintenance of remission, cumulative doses of cortisone and adverse effects of treatment will be analyzed at the 52nd week of the introduction of corticosteroid therapy. An interim analysis is planned at S28.
    Detailed Description
    Treatment of giant cell arteritis (GCA) relies on the use of glucocorticoids (GC), with a very good clinical response at treatment initiation. However, relapses at GC tapering are frequent. GCA population is elderly, frequently over 80 years, and is especially affected by GC-related side effects, that increase proportionally with treatment duration. Thus, metabolic, musculo-skeletal, infectious or neuro-psychiatric complications are frequent during prolonged GC use. After GC introduction, gradual tapering is scheduled, provided the disease remains clinically and biologically controlled. In France, guidelines recommend tapering GC on an 18-24 months timeframe, while other countries, such as the USA, usually taper GC over a shorter period, often 6-8 months. Few comparative data exist on the relapse rates or the GC-related side effects in both settings. In this prospective multicenter study, two GC-tapering schedules are planned: patients in one arm (short treatment) will be treated for 28 weeks, while patients in the second arm will be treated for 52 weeks. Each starting dose of GC and tapering doses will be adapted to body weight. The primary endpoint is to compare the remission rate without relapse at W52 between the two groups and the secondary endpoints are: 1) cumulative GC doses at W52; 2) GC-related side effects and 3) number of relapses (minor and severe) in both arms at W52. The results of this study might considerably modify future French clinical practice if investigators confirm that a shorter GC treatment does not significantly impact the disease course while reducing GC-related side effects.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Giant Cell Arteritis
    Keywords
    Giant Cell Arteritis, Horton disease, Corticosteroids treatment, Prednisone, Relapse, Side effect, Cumulative doses

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 3
    Interventional Study Model
    Parallel Assignment
    Masking
    None (Open Label)
    Allocation
    Randomized
    Enrollment
    150 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Short tapering corticosteroids
    Arm Type
    Experimental
    Arm Description
    Corticosteroid taper over 28 weeks
    Arm Title
    Long tapering corticosteroids
    Arm Type
    Active Comparator
    Arm Description
    Corticosteroid taper over 52 weeks
    Intervention Type
    Drug
    Intervention Name(s)
    Corticosteroids for Systemic Use
    Intervention Description
    Corticosteroids tapering over 28 weeks: J0 = 0,7 mg/kg S2 = 0,6 mg/kg S4 = 0,5 mg/kg S6 = 0,4 mg/kg S8 = 0,3 mg/kg S10 = 0,25 mg/kg S12 = 0,2 mg/kg S14 = 0,15 mg/kg S16 = 0,15 mg/kg S20 = 0,1 mg/kg S24 = 0,05 mg/kg S28 = 0 mg/kg Corticosteroids tapering over 52 weeks: J0 = 0,7 mg/kg S2 = 0,6 mg/kg S4 = 0,6 mg/kg S6 = 0,5 mg/kg S8 = 0,4 mg/kg S10 = 0,3 mg/kg S12 = 0,25 mg/kg S14 = 0,2 mg/kg S16 = 0,175 mg/kg S20 = 0,15 mg/kg S24 = 0,125 mg/kg S28 = 0,01 mg/kg S32 to S52: - 1mg per month
    Primary Outcome Measure Information:
    Title
    Patient in complete remission over a follow up of 52 weeks, without relapse
    Time Frame
    Baseline up to 52 weeks
    Secondary Outcome Measure Information:
    Title
    First relapses rate at S28 and S52
    Time Frame
    Weeks 28 and 52
    Title
    Second relapses rate at S28 and S52
    Time Frame
    Weeks 28 and 52
    Title
    Delay between first and second relapses
    Time Frame
    Baseline up to 52 weeks
    Title
    Cumulative and the average dose of prednisone used
    Time Frame
    Weeks 28 and 52
    Title
    Number of patient with corticosteroids dependence at week 52
    Time Frame
    Baseline up to 52 weeks
    Title
    Safety according CTCAE v5.0
    Time Frame
    Baseline up to 52 weeks

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    50 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Age ≥ 50 years Patient with temporal arteritis giant cell match 2 of the 4 criteria of the American College of Rheumatology (ACR) that given : a temporal artery biopsy compatible with a diagnosis of CAG or an abdominal thoracic aortitis diagnosed by Angio CT, MR angiography or PET scanner or Echo Doppler compatible with a diagnosis of CAG Oral corticosteroid treatment started up to 14 days, the initial dose is less or equal to 1 mg / Kg Patient wo has given its written consent Patient affiliated with a social security Exclusion Criteria: Subjects checking one of the criteria for non-inclusion may be eligible to participate in the research. These criteria may include: Early treatment of CAG disease with a dose> 1 mg / kg whatever the duration Corticosteroids already started over 14 days Giant arteritis cell on relapse dementia syndrome No compliant patient Patients who live more than 150 km from the investigation center Person under judicial protection, guardianship Hypersensitivity to prednisone or any of its excipients Infection requiring an systemic treatment Evolutive viroses (Hepatitis, Herpes, varicella-zoster virus) Immunization with live vaccines / mitigated during the 8 weeks preceding inclusion Pregnancy, breastfeeding women or women of childbearing potential not using contraception
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Hubert De BOYSSON, MD
    Phone
    02 31 06 57 32
    Ext
    +33
    Email
    deboysson-h@chu-caen.fr
    First Name & Middle Initial & Last Name or Official Title & Degree
    Audrey SULTAN, PhD
    Phone
    02 31 06 33 58
    Ext
    +33
    Email
    sultan-a@chu-caen.fr
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Hubert De BOYSSON, MD
    Organizational Affiliation
    University Hospital, Caen
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Plan to Share IPD
    No
    IPD Sharing Plan Description
    All individual data will be analyzed in University Hospital, Caen
    Citations:
    PubMed Identifier
    26833145
    Citation
    Bienvenu B, Ly KH, Lambert M, Agard C, Andre M, Benhamou Y, Bonnotte B, de Boysson H, Espitia O, Fau G, Fauchais AL, Galateau-Salle F, Haroche J, Heron E, Lapebie FX, Liozon E, Luong Nguyen LB, Magnant J, Manrique A, Matt M, de Menthon M, Mouthon L, Puechal X, Pugnet G, Quemeneur T, Regent A, Saadoun D, Samson M, Sene D, Smets P, Yelnik C, Sailler L, Mahr A; Groupe d'Etude Francais des Arterites des gros Vaisseaux, under the Aegis of the Filiere des Maladies Auto-Immunes et Auto-Inflammatoires Rares. Management of giant cell arteritis: Recommendations of the French Study Group for Large Vessel Vasculitis (GEFA). Rev Med Interne. 2016 Mar;37(3):154-65. doi: 10.1016/j.revmed.2015.12.015. Epub 2016 Jan 29.
    Results Reference
    background
    PubMed Identifier
    28324917
    Citation
    de Boysson H, Aouba A. Abatacept as Adjunctive Therapy for the Treatment of Giant Cell Arteritis: Comment on the Article by Langford et al. Arthritis Rheumatol. 2017 Jul;69(7):1504. doi: 10.1002/art.40105. Epub 2017 May 10. No abstract available.
    Results Reference
    background
    PubMed Identifier
    20693273
    Citation
    van der Goes MC, Jacobs JW, Boers M, Andrews T, Blom-Bakkers MA, Buttgereit F, Caeyers N, Cutolo M, Da Silva JA, Guillevin L, Kirwan JR, Rovensky J, Severijns G, Webber S, Westhovens R, Bijlsma JW. Monitoring adverse events of low-dose glucocorticoid therapy: EULAR recommendations for clinical trials and daily practice. Ann Rheum Dis. 2010 Nov;69(11):1913-9. doi: 10.1136/ard.2009.124958. Epub 2010 Aug 6.
    Results Reference
    background
    PubMed Identifier
    14558057
    Citation
    Proven A, Gabriel SE, Orces C, O'Fallon WM, Hunder GG. Glucocorticoid therapy in giant cell arteritis: duration and adverse outcomes. Arthritis Rheum. 2003 Oct 15;49(5):703-8. doi: 10.1002/art.11388.
    Results Reference
    background

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    Giant Cell Arteritis: Comparison Between Two Standardized Corticosteroids Tapering

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