Evaluation of Spironolactone Efficacy in Patient with Rheumatoid Arthritis (RA)

NCT05092984 | Recruiting Phase 3

• 2 other identifiers: 81542021-003958-23
• Study Type: interventional
• Target: 154
• Locations: 1 country
• Sites: 1

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)

Conditions

Rheumatoid Arthritis

Keywords

rheumatoid arthritis; cardiovascular event; spironolactone; randomized controlled trial

Outcome Measures

Primary Outcomes (1)

• Proportion of patients achieving DAS28-CRP < 3.2, comparison between spironolactone and placebo arms.

  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.

  at 3 months

Secondary Outcomes (48)

• Adverse events / Serious adverse events rate in each arm

  6 months

• NT-proBNP level

  Day 0

• NT-proBNP level

  3 months

• NT-proBNP level

  6 months

• Cardiac parameters: QRS duration (ms)

  Day 0

Study Arms (2)

Spironolactone

EXPERIMENTAL

Drug: Spironolactone

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Spironolactone DRUG

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.

Also known as: Spironolactone Mylan 25mg

Spironolactone

Placebo DRUG

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.

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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 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
• breastfeeding
• 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)

Sponsors & Collaborators

• University Hospital, Strasbourg, France: lead

Study Sites (1)

University Hospital, Strasbourg, France

Strasbourg, Alsace, 67000, France

RECRUITING

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

Spironolactone

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Lactones; Organic Chemicals; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Jacques-Eric GOTTENBERG, MD, PhD

  University Hospital, Strasbourg, France

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jacques-Eric GOTTENBERG, Professor

CONTACT

3 88 12 79 53; jacques-eric.gottenberg@chru-strasbourg.fr

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 28, 2021
• First Posted: October 26, 2021
• Study Start: June 22, 2022
• Primary Completion: March 1, 2026
• Study Completion: March 1, 2026
• Last Updated: March 12, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)