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
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
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
NCT ID
NCT04012905
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
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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