STAR: Comparison of Two Strategies of Glucocorticoid Withdrawal in Rheumatoid Arthritis Patients

Sponsor

University Hospital, Toulouse (Other)

Overall Status

Completed

CT.gov ID

NCT02997605

Collaborator

(none)

102

Enrollment

Locations

Arms

59.9

Actual Duration (Months)

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
RheumatoId Arthritis	Drug: GlucoCorticoid	Phase 4

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).

Study Design

Study Type:

Interventional

Actual Enrollment :

102 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Care Provider, Investigator)

Primary Purpose:

Supportive Care

Official Title:

Comparison of Two Strategies of Glucocorticoid Withdrawal in Rheumatoid Arthritis Patients in Low Disease Activity or Remission.

Actual Study Start Date :

Jan 31, 2017

Actual Primary Completion Date :

Jan 27, 2022

Actual Study Completion Date :

Jan 27, 2022

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Glucocorticoid (GC) tapering "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.	Drug: GlucoCorticoid 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. Other Names: Prednisone, Hydrocortisone
Active Comparator: Hydrocortisone replacer "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.	Drug: GlucoCorticoid 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. Other Names: Prednisone, Hydrocortisone

Arm

Intervention/Treatment

Active Comparator: Glucocorticoid (GC) tapering

"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.

Drug: GlucoCorticoid

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.

Other Names:

Prednisone, Hydrocortisone

Active Comparator: Hydrocortisone replacer

"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.

Drug: GlucoCorticoid

Other Names:

Prednisone, Hydrocortisone

Outcome Measures

Primary Outcome Measures

proportion of patients who could withdraw from prednisone and hydrocortisone at one year [one year after a progressive decrease of Glucocorticoids or hydrocortisone replacement]
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 [one year after a progressive decrease of Glucocorticoids or hydrocortisone replacement]
To compare the proportion of patients who could withdraw from prednisone whatever the additional hydrocortisone associated treatment.
proportion of patients with acute adrenal insufficiency [one year]
To compare the proportion of patients with acute adrenal insufficiency at one year between the two groups.
proportion of patients with biological adrenal insufficiency [one year]
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 [one year]
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. [one year]
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) [one year]
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 [7 and 12 months]
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) [4, 7 months and 1 year]
To compare the medians of HAQ at 4, 7 months and one year between the groups.
medians of Rheumatoid Arthritis Impact of Disease (RAID) [4, 7 months and 1 year]
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) [4, 7 months and 1 year]
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) [4, 7 months and 1 year]
To compare the medians of FACIT-F at 4, 7 months and one year between the groups.
proportion of patients with Serious Adverse events [1 year]
To compare the proportion of patients with Serious Adverse events at one year between the groups.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts 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.

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Bordeaux University Hospital	Bordeaux	France
2	Brest University Hospital	Brest	France
3	Jean Rougier Hospital	Cahors	France
4	Clermont-Ferrand Hospital	Clermont-Ferrand	France
5	Bicêtre Hospital	Le Kremlin-Bicêtre	France
6	Lille Hospital	Lille	France
7	Limoges Hospital	Limoges	France
8	Montpellier Hospital	Montpellier	France
9	Pasteur Hospital	Nice	France
10	Orléans Hospital	Orléans	France
11	Bichat Hospital	Paris	France
12	Cochin Hospital	Paris	France
13	La Pitié-Salpétrière	Paris	France
14	Lyon Sud Hopsital	Pierre-Bénite	France
15	Saint-Etienne Hospital	Saint-Étienne	France
16	Strasbourg Hospital	Strasbourg	France
17	Hospital Pierre-Paul Riquet	Toujouse	France	31059

Sponsors and Collaborators

University Hospital, Toulouse

Investigators

Study Chair: Adeline RUYSSEN-WITRAND, MD, PhD, University Hospital of Toulouse, Rheumatology Center
Study Chair: Arnaud CONSTANTIN, MD, PhD, University Hospital of Toulouse, Rheumatology Center