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

Обзор

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)

Подробное описание

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.

Вмешательства

• Препарат 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.
• Препарат 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.

Первичные конечные точки

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

Вторичные конечные точки (12)

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

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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)

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Двойное слепое

Основная цель

Лечение

Центры проведения

Франция · 1 центр

• University Hospital, Strasbourg, France — Strasbourg

Идентификаторы

NCT: NCT05092984 · 8154 · 2021-003958-23

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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