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

October 13, 2020 updated by: University Hospital, Caen

A Randomized, Controled, Open Label Trial: Comparison Between Two Standardized Corticosteroids Tapering, Respectively Short (North American) and Long (European), in Giant Cell Arteritis

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.

Study Overview

Status

Not yet recruiting

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.

Study Type

Interventional

Enrollment (Anticipated)

150

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

50 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Short tapering corticosteroids
Corticosteroid taper over 28 weeks

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

Active Comparator: Long tapering corticosteroids
Corticosteroid taper over 52 weeks

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Patient in complete remission over a follow up of 52 weeks, without relapse
Time Frame: Baseline up to 52 weeks
Baseline up to 52 weeks

Secondary Outcome Measures

Outcome Measure
Time Frame
First relapses rate at S28 and S52
Time Frame: Weeks 28 and 52
Weeks 28 and 52
Second relapses rate at S28 and S52
Time Frame: Weeks 28 and 52
Weeks 28 and 52
Delay between first and second relapses
Time Frame: Baseline up to 52 weeks
Baseline up to 52 weeks
Cumulative and the average dose of prednisone used
Time Frame: Weeks 28 and 52
Weeks 28 and 52
Number of patient with corticosteroids dependence at week 52
Time Frame: Baseline up to 52 weeks
Baseline up to 52 weeks
Safety according CTCAE v5.0
Time Frame: Baseline up to 52 weeks
Baseline up to 52 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

November 5, 2020

Primary Completion (Anticipated)

November 1, 2023

Study Completion (Anticipated)

January 1, 2027

Study Registration Dates

First Submitted

July 5, 2019

First Submitted That Met QC Criteria

July 8, 2019

First Posted (Actual)

July 9, 2019

Study Record Updates

Last Update Posted (Actual)

October 19, 2020

Last Update Submitted That Met QC Criteria

October 13, 2020

Last Verified

October 1, 2020

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

IPD Plan Description

All individual data will be analyzed in University Hospital, Caen

Drug and device information, study documents

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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