ALDORA: Evaluation of Spironolactone Efficacy in Patient With Rheumatoid Arthritis (RA)

Sponsor
University Hospital, Strasbourg, France (Other)
Overall Status
Recruiting
CT.gov ID
NCT05092984
Collaborator
(none)
154
1
2
20.3
7.6

Study Details

Study Description

Brief Summary

Evaluation of spironolactone, a well-known cardiological treatment, in patients with rheumatoid arthritis (RA).

The hypothesis is that spironolactone, through its anti-inflammatory and anti-fibrosis actions, decreases RA's activity. The primary objective is to assess the efficacy of spironolactone on RA activity by evaluating the proportion of patients achieving DAS28-CRP < 3.2 at 3 months (comparison between spironolactone and placebo arms). CRP (C reactive protein)

Condition or Disease Intervention/Treatment Phase
Phase 3

Detailed Description

RA is associated with increased cardiovascular (CV) morbidity and death compared to the general population due to chronic systemic inflammation. However, some cardiological drugs are effective in reducing CV mortality for high-risk patients in the general population, without inflammatory rheumatism. Open-label trials suggested that spironolactone could be an effective RA treatment due to its anti-inflammatory and anti-fibrotic properties.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
154 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
Official Title:
Evaluation of Spironolactone Efficacy in Patient With Rheumatoid Arthritis (RA)
Actual Study Start Date :
Jun 22, 2022
Anticipated Primary Completion Date :
Mar 1, 2024
Anticipated Study Completion Date :
Mar 1, 2024

Arms and Interventions

Arm Intervention/Treatment
Experimental: Spironolactone

Drug: Spironolactone
77 patients will be treated with spironolactone Mylan 25mg/day for the first 3 months of the study. Dosage adjustment can be performed according to the eGFR (estimated Glomerular Filtration Rate) concentration at baseline and the serum potassium variation. During the last 3 months of the study, all the patients will be treated with spironolactone Mylan 25mg. Dosage adjustment can be performed according to the serum potassium variation.
Other Names:
  • Spironolactone Mylan 25mg
  • Placebo Comparator: Placebo

    Drug: Placebo
    77 patients will be treated with placebo 25mg/day for the first 3 months. At inclusion, a second randomization is automatically performed in the placebo arm to determine patients receiving a dose adjustment during the study to keep the double-blind. During the last 3 months of the study, all the patients will be treated with spironolactone Mylan 25mg. Dosage adjustment can be performed according to the serum potassium variation.

    Outcome Measures

    Primary Outcome Measures

    1. Proportion of patients achieving DAS28-CRP < 3.2, comparison between spironolactone and placebo arms. [at 3 months]

      DMARDs intensification due to worsening signs and symptoms of RA at any time of the trial will be considered as treatment failure. Discontinuation of spironolactone or placebo for at least 1 month will be considered as treatment failure.

    Secondary Outcome Measures

    1. Adverse events / Serious adverse events rate in each arm [6 months]

    2. NT-proBNP level [Day 0]

      Test for B-type natriuretic peptide (BNP), used for heart failure evaluation.

    3. NT-proBNP level [3 months]

      Test for B-type natriuretic peptide (BNP), used for heart failure evaluation.

    4. NT-proBNP level [6 months]

      Test for B-type natriuretic peptide (BNP), used for heart failure evaluation.

    5. Cardiac parameters: QRS duration (ms) [Day 0]

      QRS duration (ms);

    6. Cardiac parameters: left ventricular end-diastolic volume index (mL/m2) [Day 0]

      left ventricular end-diastolic volume index (mL/m2),

    7. Cardiac parameters: left ventricular ejection fraction (%) [Day 0]

      left ventricular ejection fraction (%);

    8. Cardiac parameters: left ventricular mass index (g/m2) [Day 0]

      left ventricular mass index (g/m2);

    9. Cardiac parameters: left atrial volume index (mL/m2) [Day 0]

      left atrial volume index (mL/m2);

    10. Cardiac parameters: early mitral flow [Day 0]

      early mitral flow;

    11. Cardiac parameters: velocity (E) (m/s) [Day 0]

      velocity (E) (m/s);

    12. Cardiac parameters: late (atrial) mitral flow velocity (A) (m/s) [Day 0]

      late (atrial) mitral flow velocity (A) (m/s);

    13. Cardiac parameters: E/A ratio [Day 0]

      E/A ratio;

    14. Cardiac parameters: E/ early diastolic tissue velocity (e') [Day 0]

      E/ early diastolic tissue velocity (e');

    15. Cardiac parameters: tricuspid annular plane systolic excursion [Day 0]

      tricuspid annular plane systolic excursion

    16. Cardiac parameters: QRS duration (ms) [3 months]

      QRS duration (ms);

    17. Cardiac parameters: left ventricular end-diastolic volume index (mL/m2) [3 months]

      left ventricular end-diastolic volume index (mL/m2),

    18. Cardiac parameters: left ventricular ejection fraction (%) [3 months]

      left ventricular ejection fraction (%);

    19. Cardiac parameters: left ventricular mass index (g/m2) [3 months]

      left ventricular mass index (g/m2)

    20. Cardiac parameters: left atrial volume index (mL/m2) [3 months]

      left atrial volume index (mL/m2);

    21. Cardiac parameters: early mitral flow [3 months]

      early mitral flow;

    22. Cardiac parameters: velocity (E) (m/s) [3 months]

      velocity (E) (m/s);

    23. Cardiac parameters: late (atrial) mitral flow velocity (A) (m/s) [3 months]

      late (atrial) mitral flow velocity (A) (m/s);

    24. Cardiac parameters: E/A ratio [3 months]

      E/A ratio;

    25. Cardiac parameters: E/ early diastolic tissue velocity (e') [3 months]

      E/ early diastolic tissue velocity (e')

    26. Cardiac parameters: tricuspid annular plane systolic excursion [3 months]

      tricuspid annular plane systolic excursion

    27. CDAI score [Day 0]

      Clinical Disease Activity Index for Rheumatoid Arthritis; 0-76; From 0.0 to 2.8: remission From 2.9 to 10.0: low activity From 10.1 to 22.0: moderate activity From 22.1 to 76.0: high activity

    28. CDAI score [3 months]

      Clinical Disease Activity Index for Rheumatoid Arthritis; 0-76; From 0.0 to 2.8: remission From 2.9 to 10.0: low activity From 10.1 to 22.0: moderate activity From 22.1 to 76.0: high activity

    29. CDAI score [6 months]

      Clinical Disease Activity Index for Rheumatoid Arthritis; 0-76; From 0.0 to 2.8: remission From 2.9 to 10.0: low activity From 10.1 to 22.0: moderate activity From 22.1 to 76.0: high activity

    30. Proportion of patients achieving DAS28-CRP < 3.2 [6 months]

    31. EULAR/ACR 20 2010 classification score [3 months]

      American College of Rheumatology 20/50/70 criteria

    32. EULAR/ACR 50 2010 classification score [3 months]

      American College of Rheumatology 20/50/70 criteria

    33. EULAR/ACR 70 2010 classification score [3 months]

      American College of Rheumatology 20/50/70 criteria

    34. Boolean remission score [3 months]

    35. EULAR/ACR 20 2010 classification score [6 months]

      American College of Rheumatology 20/50/70 criteria

    36. EULAR/ACR 50 2010 classification score [6 months]

      American College of Rheumatology 20/50/70 criteria

    37. EULAR/ACR 70 2010 classification score [6 months]

      American College of Rheumatology 20/50/70 criteria

    38. Boolean remission score [6 months]

    39. Concomitant treatment modification [3 months]

      Assess the change of concomitant treatments. In case of lack efficacy with clinical symptoms requiring the dosage modification of the current DMARD or the introduction of a new DMARD, the investigator is free to choose the best treatment for the patient. Nevertheless, DMARDs intensification due to worsening signs and symptoms of at any time of the trial will be considered as treatment failure.

    40. Concomitant treatment modification [6 months]

      Assess the change of concomitant treatments. In case of lack efficacy with clinical symptoms requiring the dosage modification of the current DMARD or the introduction of a new DMARD, the investigator is free to choose the best treatment for the patient. Nevertheless, DMARDs intensification due to worsening signs and symptoms of at any time of the trial will be considered as treatment failure.

    41. Treatment account (treatment boxes and patient diary) [3 months]

    42. Treatment account (treatment boxes and patient diary) [6 months]

    43. RAPID 3 (routine assessment of patient index data 3) [Day 0]

      RAPID3 : Index to asses and monitor patients with RA

    44. RAPID 3 (routine assessment of patient index data 3) [3 months]

      RAPID3 : Index to asses and monitor patients with RA

    45. RAPID 3 (routine assessment of patient index data 3) [6 months]

      RAPID3 : Index to asses and monitor patients with RA

    46. HAQ scores [Day 0]

      HAQ : Health Assessment Questionnaire

    47. HAQ scores [3 months]

      HAQ : Health Assessment Questionnaire

    48. HAQ scores [6 months]

      HAQ : Health Assessment Questionnaire

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • patients 18 years of age and over

    • diagnosis of RA according to EULAR/ACR 2010 classification criteria

    • active RA: DAS28-CRP ≥ 3.2

    • insufficient response despite a stable DMARD treatment (cDMARD/tsDMARD(targeted synthetic DMARD)/bDMARD) ≥ 12 weeks

    • stable dose of corticosteroids for at least 4 weeks prior to inclusion

    • patient able to understand the objectives and risks of the study and to provide a written informed consent to participate in the study, dated and signed before initiating any trial-related procedure

    • patient having been informed about the results of the preliminary medical visit

    • if woman of childbearing, they should have no desire to procreate for the duration of their participation in the study, agreeing to use an effective contraception method* during the study and until 5 days following the last visit or last dose of treatment in case of early stop; acceptable birth control methods:

    • *progestogen-only oral hormonal contraception, where inhibition of ovulation is not the primary mode of action

    • *male or female condom with or without spermicide

    • *cap, diaphragm or sponge with spermicide

    • *a combination of male condom with either cap, diaphragm or sponge with spermicide (double barrier methods) are also considered acceptable, but not highly effective, birth control methods

    • affiliation to a social security regime

    Exclusion Criteria:
    • severe or acute renal insufficiency, defined by eGFR < 30 mL/min

    • hyperkalemia, with K+ > 5,1 mmol/L

    • end-stage liver failure, cirrhosis

    • hypersensitivity to the active ingredients, to sulfonamides or intolerance to any of the excipients including lactose

    • Addison's disease

    • patient currently being treated with spironolactone, or previous spironolactone treatment in the last 3 months

    • concomitant treatment with mitotane, other potassium-sparing diuretics (alone or in combination) such as amiloride, potassium canrenoate, eplerenone, triamterene

    • other inflammatory arthritis except associated Sjögren's syndrome

    • pregnancy (women of childbearing potential : positive blood pregnancy test at the inclusion visit (V0))

    • breastfeeding

    • participation in a clinical study with an investigational product within 4 weeks prior to the start of the study treatment or still under the exclusion period

    • unwillingness or incapacity to adhere to study protocol (language barriers, cognitive disorders, etc.).

    • subjects who are compulsorily detained for treatment of either a psychiatric or physical (e.g., infectious disease) illness.

    • patient who cannot be followed for 6 months

    • patient over the age of legal majority who are protected, or deprived of liberty by judicial or administrative decision (vulnerable subjects)

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 University Hospital, Strasbourg, France Strasbourg Alsace France 67000

    Sponsors and Collaborators

    • University Hospital, Strasbourg, France

    Investigators

    • Principal Investigator: Jacques-Eric GOTTENBERG, MD, PhD, University Hospital, Strasbourg, France

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    University Hospital, Strasbourg, France
    ClinicalTrials.gov Identifier:
    NCT05092984
    Other Study ID Numbers:
    • 8154
    • 2021-003958-23
    First Posted:
    Oct 26, 2021
    Last Update Posted:
    Aug 18, 2022
    Last Verified:
    Aug 1, 2022
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by University Hospital, Strasbourg, France
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Aug 18, 2022