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

Phase 3RecruitingNCT05092984

University Hospital, Strasbourg, France154 enrolled

Overview

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)

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

154

Conditions

Rheumatoid Arthritis

Interventions

SpironolactoneDRUG

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.

PlaceboDRUG

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.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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 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)

Locations (1)

University Hospital, Strasbourg, France

Strasbourg, Alsace, France

RECRUITING

Outcomes

Primary Outcomes

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.

Time frame: at 3 months

Secondary Outcomes

Adverse events / Serious adverse events rate in each arm

Time frame: 6 months

NT-proBNP level

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

Time frame: Day 0

NT-proBNP level

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

Time frame: 3 months

NT-proBNP level

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

Time frame: 6 months

Cardiac parameters: QRS duration (ms)

QRS duration (ms);

Time frame: Day 0

Cardiac parameters: left ventricular end-diastolic volume index (mL/m2)

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

Time frame: Day 0

Cardiac parameters: left ventricular ejection fraction (%)

left ventricular ejection fraction (%);

Time frame: Day 0

Central Contacts

Jacques-Eric GOTTENBERG, Professor

CONTACT

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

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Cardiac parameters: left ventricular mass index (g/m2)

left ventricular mass index (g/m2);

Time frame: Day 0

Cardiac parameters: left atrial volume index (mL/m2)

left atrial volume index (mL/m2);

Time frame: Day 0

Cardiac parameters: early mitral flow

early mitral flow;

Time frame: Day 0

Cardiac parameters: velocity (E) (m/s)

velocity (E) (m/s);

Time frame: Day 0

Cardiac parameters: late (atrial) mitral flow velocity (A) (m/s)

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

Time frame: Day 0

Cardiac parameters: E/A ratio

E/A ratio;

Time frame: Day 0

Cardiac parameters: E/ early diastolic tissue velocity (e')

E/ early diastolic tissue velocity (e');

Time frame: Day 0

Cardiac parameters: tricuspid annular plane systolic excursion

tricuspid annular plane systolic excursion

Time frame: Day 0

Cardiac parameters: QRS duration (ms)

QRS duration (ms);

Time frame: 3 months

Cardiac parameters: left ventricular end-diastolic volume index (mL/m2)

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

Time frame: 3 months

Cardiac parameters: left ventricular ejection fraction (%)

left ventricular ejection fraction (%);

Time frame: 3 months

Cardiac parameters: left ventricular mass index (g/m2)

left ventricular mass index (g/m2)

Time frame: 3 months

Cardiac parameters: left atrial volume index (mL/m2)

left atrial volume index (mL/m2);

Time frame: 3 months

Cardiac parameters: early mitral flow

early mitral flow;

Time frame: 3 months

Cardiac parameters: velocity (E) (m/s)

velocity (E) (m/s);

Time frame: 3 months

Cardiac parameters: late (atrial) mitral flow velocity (A) (m/s)

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

Time frame: 3 months

Cardiac parameters: E/A ratio

E/A ratio;

Time frame: 3 months

Cardiac parameters: E/ early diastolic tissue velocity (e')

E/ early diastolic tissue velocity (e')

Time frame: 3 months

Cardiac parameters: tricuspid annular plane systolic excursion

tricuspid annular plane systolic excursion

Time frame: 3 months

CDAI score

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

Time frame: Day 0

CDAI score

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

Time frame: 3 months

CDAI score

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

Time frame: 6 months

Proportion of patients achieving DAS28-CRP < 3.2

Time frame: 6 months

EULAR/ACR 20 2010 classification score