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

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

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.

Study Overview

• Status: Completed
• Conditions: RheumatoId Arthritis
• Intervention / Treatment: Drug: GlucoCorticoid

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 Type: Interventional
• Enrollment (Actual): 102
• Phase: Phase 4

Contacts and Locations

Study Locations

• France
  • Bordeaux, France
    • Bordeaux university hospital
  • Brest, France
    • Brest University Hospital
  • Cahors, France
    • Jean Rougier Hospital
  • Clermont-Ferrand, France
    • Clermont-Ferrand Hospital
  • Le Kremlin-Bicêtre, France
    • Bicetre Hospital
  • Lille, France
    • Lille Hospital
  • Limoges, France
    • Limoges hospital
  • Montpellier, France
    • Montpellier Hospital
  • Nice, France
    • Pasteur Hospital
  • Orléans, France
    • Orléans Hospital
  • Paris, France
    • La Pitié-Salpêtrière
  • Paris, France
    • Cochin Hospital
  • Paris, France
    • Bichat Hospital
  • Pierre-Bénite, France
    • Lyon Sud Hopsital
  • Saint-Étienne, France
    • Saint-Etienne Hospital
  • Strasbourg, France
    • Strasbourg Hospital
  • Toujouse, France, 31059
    • Hospital Pierre-Paul Riquet

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	one year after a progressive decrease of Glucocorticoids or hydrocortisone replacement

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	one year after a progressive decrease of Glucocorticoids or hydrocortisone replacement
proportion of patients with acute adrenal insufficiency	To compare the proportion of patients with acute adrenal insufficiency at one year between the two groups.	one year
proportion of patients with biological adrenal insufficiency	To compare the proportion of patients with biological adrenal insufficiency at one year between the two groups.	one year
proportion of patients needing extra prednisone to control flares	To compare the proportion of patients needing extra prednisone to control flares	one year
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.	one year
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.	one year
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.	7 and 12 months
medians of Health Assessment Questionnaire (HAQ)	To compare the medians of HAQ at 4, 7 months and one year between the groups.	4, 7 months and 1 year
medians of Rheumatoid Arthritis Impact of Disease (RAID)	To compare the medians of RAID at 4, 7 months and one year between the groups.	4, 7 months and 1 year
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.	4, 7 months and 1 year
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.	4, 7 months and 1 year
proportion of patients with Serious Adverse events	To compare the proportion of patients with Serious Adverse events at one year between the groups.	1 year

Collaborators and Investigators

• Sponsor: 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

Study record dates

Study Major Dates

• Study Start (Actual): January 31, 2017
• Primary Completion (Actual): January 27, 2022
• Study Completion (Actual): January 27, 2022

Study Registration Dates

• First Submitted: December 15, 2016
• First Submitted That Met QC Criteria: December 19, 2016
• First Posted (Estimate): December 20, 2016

Study Record Updates

• Last Update Posted (Actual): March 2, 2022
• Last Update Submitted That Met QC Criteria: February 28, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Keywords: remission; low disease activity
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid; Physiological Effects of Drugs; Anti-Inflammatory Agents; Antineoplastic Agents; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Prednisone; Hydrocortisone; Glucocorticoids
• Other Study ID Numbers: RC31/15/7824; PHRC (2001/1939); 2016-001618-18 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No