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Comparison of Two Strategies of Glucocorticoid Withdrawal in Rheumatoid Arthritis Patients (STAR)

Primary Purpose

RheumatoId Arthritis

Status
Completed
Phase
Phase 4
Locations
France
Study Type
Interventional
Intervention
GlucoCorticoid
Sponsored by
University Hospital, Toulouse
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional supportive care trial for RheumatoId Arthritis focused on measuring low disease activity, remission

Eligibility Criteria

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

Inclusion Criteria:

  • Patients ≥ 18 years old.
  • Fulfilling the 2010 American College of Rheumatology (ACR)/EULAR criteria for RA.
  • Treated with a stable dose of Synthetic Disease Modifying Anti-Rheumatic Drugs (sDMARD) or Biological Disease Modifying Anti-Rheumatic Drug (bDMARD) for at least 3 months.
  • Who have been treated with prednisone or prednisolone for at least 6 months.
  • With a stable dose of prednisone or prednisolone of 5mg/day for at least 3 months.
  • With a DAS28 ≤3.2 for at least 3 months.
  • Patients with health insurance
  • Patients who have signed a written informed consent form.

Exclusion Criteria:

  • Any chronic condition that would need long term corticoid use (e.g. chronic lung diseases).
  • Evidence of a flare within the last 3 months.
  • Evidence of an allergy or intolerance to hydrocortisone or prednisone.
  • Chronic idiopathic, or autoimmune clinical adrenal insufficiency.
  • GC joint injections within the last 3 months or scheduled in the next 3 months.
  • Any GC intake expected more than >5mg/day within the next 12 months.
  • Association with sultopride and with live vaccines
  • Significant trauma or major surgery within the 3 months prior to the baseline visit.
  • Scheduled surgery in the next 12 months.
  • Fibromyalgia.
  • Foreseeable poor compliance with the strategy.
  • Patient with any condition that would prevent participation in the study and completion of the study procedures, including language limitation.
  • Alcohol and/or drug misuse as determined by the investigator.
  • Pregnancy or breastfeeding.
  • Patient is not willing to sign the informed consent.
  • Juridical Protection
  • DAS28>3.2 after one month of a stable dose of prednisone 5 mg/day.

Sites / Locations

  • Bordeaux University Hospital
  • Brest University Hospital
  • Jean Rougier Hospital
  • Clermont-Ferrand Hospital
  • Bicêtre Hospital
  • Lille Hospital
  • Limoges Hospital
  • Montpellier Hospital
  • Pasteur Hospital
  • Orléans Hospital
  • Bichat Hospital
  • Cochin Hospital
  • La Pitié-Salpétrière
  • Lyon Sud Hopsital
  • Saint-Etienne Hospital
  • Strasbourg Hospital
  • Hospital Pierre-Paul Riquet

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Active Comparator

Arm Label

Glucocorticoid (GC) tapering

Hydrocortisone replacer

Arm Description

"GC tapering group": patients will be asked to taper prednisone taken every morning at 8.00 AM by decreasing the daily dose by 1 mg every month as soon as they are in remission or Low Disease Activity (LDA). In addition they will receive a placebo of 20 mg/day of hydrocortisone (10 mg at 8.00 AM, 10 mg at 12.00 AM) for 3 months then 10 mg/day (at 8.00 AM) of hydrocortisone placebo for 3 months before discontinuing the hydrocortisone placebo.

"Hydrocortisone replacer group": patients will replace prednisone with 20 mg of hydrocortisone on a daily basis (10 mg at 8.00 AM, 10 mg at 12.00 AM) for 3 months then 10 mg daily (at 8.00 AM) for 3 months then stop as soon as they are in remission or LDA, as well as a prednisone placebo (at 8.00 AM) with a schedule to taper the prednisone placebo by 1mg/day every month until discontinuation.

Outcomes

Primary Outcome Measures

proportion of patients who could withdraw from prednisone and hydrocortisone at one year
To compare a prednisone tapering strategy to a hydrocortisone replacement strategy on the success rate of prednisone and hydrocortisone withdrawal at one year in Rheumatoid Arthritis patients in low disease activity or remission.

Secondary Outcome Measures

proportion of patients who could withdraw from prednisone
To compare the proportion of patients who could withdraw from prednisone whatever the additional hydrocortisone associated treatment.
proportion of patients with acute adrenal insufficiency
To compare the proportion of patients with acute adrenal insufficiency at one year between the two groups.
proportion of patients with biological adrenal insufficiency
To compare the proportion of patients with biological adrenal insufficiency at one year between the two groups.
proportion of patients needing extra prednisone to control flares
To compare the proportion of patients needing extra prednisone to control flares
proportion of patients who have at least one flare confirmed by the investigator during the protocol.
To compare the proportion of patients who have at least one flare confirmed by the investigator during the protocol.
area under the curve of means of the FLARE (Flare Assessment in Rheumatoid Arthritis)
To compare the area under the curve of the means of the FLARE (Flare Assessment in Rheumatoid Arthritis) at one year with a self-assessment questionnaire.
proportion of patients in DAS28 remission and in DAS28 low disease activity
To compare the proportion of patients in DAS28 remission and in DAS28 low disease activity at 7 and 12 months between the groups.
medians of Health Assessment Questionnaire (HAQ)
To compare the medians of HAQ at 4, 7 months and one year between the groups.
medians of Rheumatoid Arthritis Impact of Disease (RAID)
To compare the medians of RAID at 4, 7 months and one year between the groups.
medians of EuroQol 5-dimensional Descriptive system (EQ-5D)
To compare the medians of EQ-5D at 4, 7 months and one year between the groups.
medians of Functional Assessment of Chronic Illness Therapy - Fatigue Scale FACIT-F)
To compare the medians of FACIT-F at 4, 7 months and one year between the groups.
proportion of patients with Serious Adverse events
To compare the proportion of patients with Serious Adverse events at one year between the groups.

Full Information

First Posted
December 15, 2016
Last Updated
February 28, 2022
Sponsor
University Hospital, Toulouse
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1. Study Identification

Unique Protocol Identification Number
NCT02997605
Brief Title
Comparison of Two Strategies of Glucocorticoid Withdrawal in Rheumatoid Arthritis Patients
Acronym
STAR
Official Title
Comparison of Two Strategies of Glucocorticoid Withdrawal in Rheumatoid Arthritis Patients in Low Disease Activity or Remission.
Study Type
Interventional

2. Study Status

Record Verification Date
February 2022
Overall Recruitment Status
Completed
Study Start Date
January 31, 2017 (Actual)
Primary Completion Date
January 27, 2022 (Actual)
Study Completion Date
January 27, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital, Toulouse

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
The purpose of this study is to compare the proportion of patients who could withdraw from prednisone and hydrocortisone one year after a progressive decrease of GC (GC tapering) or a hydrocortisone replacement therapy in rheumatoid arthritis in remission or low disease activity.
Detailed Description
French multicenter double-blind controlled parallel-group randomized clinical trial Phase IV assessing whether a hydrocortisone replacement therapy could increase the success rate of GC withdrawal at one year, in patients with Rheumatoid Arthritis in low disease activity or remission, in comparison to progressive decrease of GC (GC tapering).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
RheumatoId Arthritis
Keywords
low disease activity, remission

7. Study Design

Primary Purpose
Supportive Care
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
102 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Glucocorticoid (GC) tapering
Arm Type
Active Comparator
Arm Description
"GC tapering group": patients will be asked to taper prednisone taken every morning at 8.00 AM by decreasing the daily dose by 1 mg every month as soon as they are in remission or Low Disease Activity (LDA). In addition they will receive a placebo of 20 mg/day of hydrocortisone (10 mg at 8.00 AM, 10 mg at 12.00 AM) for 3 months then 10 mg/day (at 8.00 AM) of hydrocortisone placebo for 3 months before discontinuing the hydrocortisone placebo.
Arm Title
Hydrocortisone replacer
Arm Type
Active Comparator
Arm Description
"Hydrocortisone replacer group": patients will replace prednisone with 20 mg of hydrocortisone on a daily basis (10 mg at 8.00 AM, 10 mg at 12.00 AM) for 3 months then 10 mg daily (at 8.00 AM) for 3 months then stop as soon as they are in remission or LDA, as well as a prednisone placebo (at 8.00 AM) with a schedule to taper the prednisone placebo by 1mg/day every month until discontinuation.
Intervention Type
Drug
Intervention Name(s)
GlucoCorticoid
Other Intervention Name(s)
Prednisone, Hydrocortisone
Intervention Description
After inclusion in the study, the first part is an open follow-up period where all patients will receive 5 mg of prednisone daily for one month. After one month, if patients still have a DAS28 ≤3.2, they will be randomized into two arms: Group 1: "GC tapering group" / Group 2: "Hydrocortisone replacement group". After randomisation, there are four scheduled visits: M4, M7, M9 and M12. Patients withdrawing from GC therapy will be instructed, that if they start feeling unwell during or after the GC tapering protocol they should not taper the steroid dose any further, but contact the centre responsible for the protocol. If GC induced adrenal insufficiency is confirmed or strongly suspected, GC replacement will be secured using hydrocortisone.
Primary Outcome Measure Information:
Title
proportion of patients who could withdraw from prednisone and hydrocortisone at one year
Description
To compare a prednisone tapering strategy to a hydrocortisone replacement strategy on the success rate of prednisone and hydrocortisone withdrawal at one year in Rheumatoid Arthritis patients in low disease activity or remission.
Time Frame
one year after a progressive decrease of Glucocorticoids or hydrocortisone replacement
Secondary Outcome Measure Information:
Title
proportion of patients who could withdraw from prednisone
Description
To compare the proportion of patients who could withdraw from prednisone whatever the additional hydrocortisone associated treatment.
Time Frame
one year after a progressive decrease of Glucocorticoids or hydrocortisone replacement
Title
proportion of patients with acute adrenal insufficiency
Description
To compare the proportion of patients with acute adrenal insufficiency at one year between the two groups.
Time Frame
one year
Title
proportion of patients with biological adrenal insufficiency
Description
To compare the proportion of patients with biological adrenal insufficiency at one year between the two groups.
Time Frame
one year
Title
proportion of patients needing extra prednisone to control flares
Description
To compare the proportion of patients needing extra prednisone to control flares
Time Frame
one year
Title
proportion of patients who have at least one flare confirmed by the investigator during the protocol.
Description
To compare the proportion of patients who have at least one flare confirmed by the investigator during the protocol.
Time Frame
one year
Title
area under the curve of means of the FLARE (Flare Assessment in Rheumatoid Arthritis)
Description
To compare the area under the curve of the means of the FLARE (Flare Assessment in Rheumatoid Arthritis) at one year with a self-assessment questionnaire.
Time Frame
one year
Title
proportion of patients in DAS28 remission and in DAS28 low disease activity
Description
To compare the proportion of patients in DAS28 remission and in DAS28 low disease activity at 7 and 12 months between the groups.
Time Frame
7 and 12 months
Title
medians of Health Assessment Questionnaire (HAQ)
Description
To compare the medians of HAQ at 4, 7 months and one year between the groups.
Time Frame
4, 7 months and 1 year
Title
medians of Rheumatoid Arthritis Impact of Disease (RAID)
Description
To compare the medians of RAID at 4, 7 months and one year between the groups.
Time Frame
4, 7 months and 1 year
Title
medians of EuroQol 5-dimensional Descriptive system (EQ-5D)
Description
To compare the medians of EQ-5D at 4, 7 months and one year between the groups.
Time Frame
4, 7 months and 1 year
Title
medians of Functional Assessment of Chronic Illness Therapy - Fatigue Scale FACIT-F)
Description
To compare the medians of FACIT-F at 4, 7 months and one year between the groups.
Time Frame
4, 7 months and 1 year
Title
proportion of patients with Serious Adverse events
Description
To compare the proportion of patients with Serious Adverse events at one year between the groups.
Time Frame
1 year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients ≥ 18 years old. Fulfilling the 2010 American College of Rheumatology (ACR)/EULAR criteria for RA. Treated with a stable dose of Synthetic Disease Modifying Anti-Rheumatic Drugs (sDMARD) or Biological Disease Modifying Anti-Rheumatic Drug (bDMARD) for at least 3 months. Who have been treated with prednisone or prednisolone for at least 6 months. With a stable dose of prednisone or prednisolone of 5mg/day for at least 3 months. With a DAS28 ≤3.2 for at least 3 months. Patients with health insurance Patients who have signed a written informed consent form. Exclusion Criteria: Any chronic condition that would need long term corticoid use (e.g. chronic lung diseases). Evidence of a flare within the last 3 months. Evidence of an allergy or intolerance to hydrocortisone or prednisone. Chronic idiopathic, or autoimmune clinical adrenal insufficiency. GC joint injections within the last 3 months or scheduled in the next 3 months. Any GC intake expected more than >5mg/day within the next 12 months. Association with sultopride and with live vaccines Significant trauma or major surgery within the 3 months prior to the baseline visit. Scheduled surgery in the next 12 months. Fibromyalgia. Foreseeable poor compliance with the strategy. Patient with any condition that would prevent participation in the study and completion of the study procedures, including language limitation. Alcohol and/or drug misuse as determined by the investigator. Pregnancy or breastfeeding. Patient is not willing to sign the informed consent. Juridical Protection DAS28>3.2 after one month of a stable dose of prednisone 5 mg/day.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Adeline RUYSSEN-WITRAND, MD, PhD
Organizational Affiliation
University Hospital of Toulouse, Rheumatology Center
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Arnaud CONSTANTIN, MD, PhD
Organizational Affiliation
University Hospital of Toulouse, Rheumatology Center
Official's Role
Study Chair
Facility Information:
Facility Name
Bordeaux University Hospital
City
Bordeaux
Country
France
Facility Name
Brest University Hospital
City
Brest
Country
France
Facility Name
Jean Rougier Hospital
City
Cahors
Country
France
Facility Name
Clermont-Ferrand Hospital
City
Clermont-Ferrand
Country
France
Facility Name
Bicêtre Hospital
City
Le Kremlin-Bicêtre
Country
France
Facility Name
Lille Hospital
City
Lille
Country
France
Facility Name
Limoges Hospital
City
Limoges
Country
France
Facility Name
Montpellier Hospital
City
Montpellier
Country
France
Facility Name
Pasteur Hospital
City
Nice
Country
France
Facility Name
Orléans Hospital
City
Orléans
Country
France
Facility Name
Bichat Hospital
City
Paris
Country
France
Facility Name
Cochin Hospital
City
Paris
Country
France
Facility Name
La Pitié-Salpétrière
City
Paris
Country
France
Facility Name
Lyon Sud Hopsital
City
Pierre-Bénite
Country
France
Facility Name
Saint-Etienne Hospital
City
Saint-Étienne
Country
France
Facility Name
Strasbourg Hospital
City
Strasbourg
Country
France
Facility Name
Hospital Pierre-Paul Riquet
City
Toujouse
ZIP/Postal Code
31059
Country
France

12. IPD Sharing Statement

Plan to Share IPD
No

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Comparison of Two Strategies of Glucocorticoid Withdrawal in Rheumatoid Arthritis Patients

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