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Comparison of Two Strategies of Glucocorticoid Withdrawal in Rheumatoid Arthritis Patients

Phase 4
Completed
Conditions
RheumatoId Arthritis
Interventions
Registration Number
NCT02997605
Lead Sponsor
University Hospital, Toulouse
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).

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
102
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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Glucocorticoid (GC) taperingGlucoCorticoid"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 replacerGlucoCorticoid"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.
Primary Outcome Measures
NameTimeMethod
proportion of patients who could withdraw from prednisone and hydrocortisone at one yearone 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
NameTimeMethod
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.

proportion of patients in DAS28 remission and in DAS28 low disease activity7 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.

proportion of patients needing extra prednisone to control flaresone year

To compare the proportion of patients needing extra prednisone to control flares

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.

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 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 events1 year

To compare the proportion of patients with Serious Adverse events at one year between the groups.

proportion of patients who could withdraw from prednisoneone 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 insufficiencyone year

To compare the proportion of patients with acute adrenal insufficiency at one year between the two groups.

proportion of patients with biological adrenal insufficiencyone year

To compare the proportion of patients with biological adrenal insufficiency at one year between the two 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.

Trial Locations

Locations (17)

Brest University Hospital

🇫🇷

Brest, France

Bordeaux University Hospital

🇫🇷

Bordeaux, France

Clermont-Ferrand Hospital

🇫🇷

Clermont-Ferrand, France

Pasteur Hospital

🇫🇷

Nice, France

Saint-Etienne Hospital

🇫🇷

Saint-Étienne, France

Strasbourg Hospital

🇫🇷

Strasbourg, France

Orléans Hospital

🇫🇷

Orléans, France

Hospital Pierre-Paul Riquet

🇫🇷

Toujouse, France

Lille Hospital

🇫🇷

Lille, France

La Pitié-Salpétrière

🇫🇷

Paris, France

Bichat Hospital

🇫🇷

Paris, France

Cochin Hospital

🇫🇷

Paris, France

Jean Rougier Hospital

🇫🇷

Cahors, France

Bicêtre Hospital

🇫🇷

Le Kremlin-Bicêtre, France

Lyon Sud Hopsital

🇫🇷

Pierre-Bénite, France

Limoges Hospital

🇫🇷

Limoges, France

Montpellier Hospital

🇫🇷

Montpellier, France

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