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

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)

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.

Interventions

• 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.
• 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.

Primary outcome measures

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

Secondary outcome measures (12)

• Adverse events / Serious adverse events rate in each arm [Time frame: 6 months]
• NT-proBNP level [Time frame: Day 0]
• NT-proBNP level [Time frame: 3 months]
• NT-proBNP level [Time frame: 6 months]
• Cardiac parameters: QRS duration (ms) [Time frame: Day 0]
• Cardiac parameters: left ventricular end-diastolic volume index (mL/m2) [Time frame: Day 0]
• Cardiac parameters: left ventricular ejection fraction (%) [Time frame: Day 0]
• Cardiac parameters: left ventricular mass index (g/m2) [Time frame: Day 0]
• Cardiac parameters: left atrial volume index (mL/m2) [Time frame: Day 0]
• Cardiac parameters: early mitral flow [Time frame: Day 0]
• Cardiac parameters: velocity (E) (m/s) [Time frame: Day 0]
• Cardiac parameters: late (atrial) mitral flow velocity (A) (m/s) [Time frame: Day 0]

Eligibility criteria

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)

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Double blind

Primary purpose

Treatment

Study locations

France · 1 center

• University Hospital, Strasbourg, France — Strasbourg

Identifiers

NCT: NCT05092984 · 8154 · 2021-003958-23

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗