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

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ClinicalTrials.gov Identifier: NCT02997605
Recruitment Status : Recruiting
First Posted : December 20, 2016
Last Update Posted : January 23, 2019
Sponsor:
Information provided by (Responsible Party):
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.

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).

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 122 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 : January 31, 2017
Estimated Primary Completion Date : December 2019
Estimated Study Completion Date : December 2019


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 Name: 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 Name: Prednisone, Hydrocortisone




Primary Outcome Measures :
  1. proportion of patients who could withdraw from prednisone and hydrocortisone at one year [ Time Frame: 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 :
  1. proportion of patients who could withdraw from prednisone [ Time Frame: 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.

  2. proportion of patients with acute adrenal insufficiency [ Time Frame: one year ]
    To compare the proportion of patients with acute adrenal insufficiency at one year between the two groups.

  3. proportion of patients with biological adrenal insufficiency [ Time Frame: one year ]
    To compare the proportion of patients with biological adrenal insufficiency at one year between the two groups.

  4. proportion of patients needing extra prednisone to control flares [ Time Frame: one year ]
    To compare the proportion of patients needing extra prednisone to control flares

  5. proportion of patients who have at least one flare confirmed by the investigator during the protocol. [ Time Frame: one year ]
    To compare the proportion of patients who have at least one flare confirmed by the investigator during the protocol.

  6. area under the curve of means of the FLARE (Flare Assessment in Rheumatoid Arthritis) [ Time Frame: 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.

  7. proportion of patients in DAS28 remission and in DAS28 low disease activity [ Time Frame: 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.

  8. medians of Health Assessment Questionnaire (HAQ) [ Time Frame: 4, 7 months and 1 year ]
    To compare the medians of HAQ at 4, 7 months and one year between the groups.

  9. medians of Rheumatoid Arthritis Impact of Disease (RAID) [ Time Frame: 4, 7 months and 1 year ]
    To compare the medians of RAID at 4, 7 months and one year between the groups.

  10. medians of EuroQol 5-dimensional Descriptive system (EQ-5D) [ Time Frame: 4, 7 months and 1 year ]
    To compare the medians of EQ-5D at 4, 7 months and one year between the groups.

  11. medians of Functional Assessment of Chronic Illness Therapy - Fatigue Scale FACIT-F) [ Time Frame: 4, 7 months and 1 year ]
    To compare the medians of FACIT-F at 4, 7 months and one year between the groups.

  12. proportion of patients with Serious Adverse events [ Time Frame: 1 year ]
    To compare the proportion of patients with Serious Adverse events at one year between the groups.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 disease with GC contraindication.
  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02997605


Contacts
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Contact: Adeline RUYSSEN-WITRAND, MD, PhD 05 61 77 56 26 ext 33 ruyssen-witrand.a@chu-toulouse.fr
Contact: Arnaud CONSTANTIN, MD, PhD 05 61 77 69 76 ext 33 constantin.a@chu-toulouse.fr

Locations
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France
Bordeaux University Hospital Recruiting
Bordeaux, France
Contact: Chirstophe RICHEZ, MD         
Brest University Hospital Recruiting
Brest, France
Contact: Alain SARAUX, MD         
Jean Rougier Hospital Not yet recruiting
Cahors, France
Contact: Slim Lassoued, MD         
Clermont-Ferrand Hospital Recruiting
Clermont-Ferrand, France
Contact: Martin SOUBRIER, MDR         
Bicêtre Hospital Recruiting
Le Kremlin-Bicêtre, France
Contact: Xavier MARIETTE, MD         
Lille Hospital Recruiting
Lille, France
Contact: René-Marc FLIPO, MD         
Limoges Hospital Recruiting
Limoges, France
Contact: Pascale Vergne-Salle, MD         
Montpellier Hospital Recruiting
Montpellier, France
Contact: Jacques MOREL, MD         
Pasteur Hospital Recruiting
Nice, France
Contact: Christian Roux, MD         
Orléans Hospital Recruiting
Orléans, France
Contact: Carine SALLIOT, MD         
Bichat Hospital Recruiting
Paris, France
Contact: Philippe DIEUDE, MD         
Cochin Hospital Recruiting
Paris, France
Contact: Yannick Allanore, md         
Principal Investigator: Minh Nguyen, MD         
La Pitié-Salpétrière Recruiting
Paris, France
Contact: Laure Gossec, MD         
Lyon Sud Hopsital Recruiting
Pierre-Bénite, France
Contact: Muriel Piperno, MD         
Saint-Etienne Hospital Recruiting
Saint-Étienne, France
Contact: Hubert Marotte, MD         
Strasbourg Hospital Recruiting
Strasbourg, France
Contact: Jacques-Eric Gottenberg, MD         
Hospital Pierre-Paul Riquet Recruiting
Toujouse, France, 31059
Contact: Adeline RUYSSEN-WITRAND, MD, PhD    05 61 77 56 26 ext 33    ruyssen-witrand.a@chu-toulouse.fr   
Contact: Arnaud CONSTANTIN, MD, PhD    05 61 77 69 76 ext 33    constantin.a@chu-toulouse.fr   
Sponsors and Collaborators
University Hospital, Toulouse
Investigators
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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

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Responsible Party: University Hospital, Toulouse
ClinicalTrials.gov Identifier: NCT02997605     History of Changes
Other Study ID Numbers: RC31/15/7824
2016-001618-18 ( EudraCT Number )
PHRC ( Other Grant/Funding Number: French Ministry of Health )
First Posted: December 20, 2016    Key Record Dates
Last Update Posted: January 23, 2019
Last Verified: January 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by University Hospital, Toulouse:
low disease activity
remission
Additional relevant MeSH terms:
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Hydrocortisone
Hydrocortisone 17-butyrate 21-propionate
Hydrocortisone acetate
Hydrocortisone hemisuccinate
Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Prednisone
Glucocorticoids
Anti-Inflammatory Agents
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents