Clinical trial NCT05092984: Evaluation of Spironolactone Efficacy in Patient with Rheumatoid Arthritis (RA)
Official title: Evaluation of Spironolactone Efficacy in Patient with Rheumatoid Arthritis (RA)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Rheumatoid Arthritis
Keywords: rheumatoid arthritis
cardiovascular event
spironolactone
randomized controlled trial
Lead sponsor: University Hospital, Strasbourg, France
Sponsor class: OTHER
First posted: 2021-10-26
Enrollment: 154
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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)

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.

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)

Primary outcomes:
measure: Proportion of patients achieving DAS28-CRP < 3.2, comparison between spironolactone and placebo arms.
timeFrame: at 3 months
Secondary outcomes:
measure: Adverse events / Serious adverse events rate in each arm
timeFrame: 6 months
measure: NT-proBNP level
timeFrame: Day 0
measure: NT-proBNP level
timeFrame: 3 months
measure: NT-proBNP level
timeFrame: 6 months
measure: Cardiac parameters: QRS duration (ms)
timeFrame: Day 0
measure: Cardiac parameters: left ventricular end-diastolic volume index (mL/m2)
timeFrame: Day 0
measure: Cardiac parameters: left ventricular ejection fraction (%)
timeFrame: Day 0
measure: Cardiac parameters: left ventricular mass index (g/m2)
timeFrame: Day 0
measure: Cardiac parameters: left atrial volume index (mL/m2)
timeFrame: Day 0
measure: Cardiac parameters: early mitral flow
timeFrame: Day 0
measure: Cardiac parameters: velocity (E) (m/s)
timeFrame: Day 0
measure: Cardiac parameters: late (atrial) mitral flow velocity (A) (m/s)
timeFrame: Day 0
measure: Cardiac parameters: E/A ratio
timeFrame: Day 0
measure: Cardiac parameters: E/ early diastolic tissue velocity (e')
timeFrame: Day 0
measure: Cardiac parameters: tricuspid annular plane systolic excursion
timeFrame: Day 0
measure: Cardiac parameters: QRS duration (ms)
timeFrame: 3 months
measure: Cardiac parameters: left ventricular end-diastolic volume index (mL/m2)
timeFrame: 3 months
measure: Cardiac parameters: left ventricular ejection fraction (%)
timeFrame: 3 months
measure: Cardiac parameters: left ventricular mass index (g/m2)
timeFrame: 3 months
measure: Cardiac parameters: left atrial volume index (mL/m2)
timeFrame: 3 months
measure: Cardiac parameters: early mitral flow
timeFrame: 3 months
measure: Cardiac parameters: velocity (E) (m/s)
timeFrame: 3 months
measure: Cardiac parameters: late (atrial) mitral flow velocity (A) (m/s)
timeFrame: 3 months
measure: Cardiac parameters: E/A ratio
timeFrame: 3 months
measure: Cardiac parameters: E/ early diastolic tissue velocity (e')
timeFrame: 3 months
measure: Cardiac parameters: tricuspid annular plane systolic excursion
timeFrame: 3 months
measure: CDAI score
timeFrame: Day 0
measure: CDAI score
timeFrame: 3 months
measure: CDAI score
timeFrame: 6 months
measure: Proportion of patients achieving DAS28-CRP < 3.2
timeFrame: 6 months
measure: EULAR/ACR 20 2010 classification score
timeFrame: 3 months
measure: EULAR/ACR 50 2010 classification score
timeFrame: 3 months
measure: EULAR/ACR 70 2010 classification score
timeFrame: 3 months
measure: Boolean remission score
timeFrame: 3 months
measure: EULAR/ACR 20 2010 classification score
timeFrame: 6 months
measure: EULAR/ACR 50 2010 classification score
timeFrame: 6 months
measure: EULAR/ACR 70 2010 classification score
timeFrame: 6 months
measure: Boolean remission score
timeFrame: 6 months
measure: Concomitant treatment modification
timeFrame: 3 months
measure: Concomitant treatment modification
timeFrame: 6 months
measure: Treatment account (treatment boxes and patient diary)
timeFrame: 3 months
measure: Treatment account (treatment boxes and patient diary)
timeFrame: 6 months
measure: RAPID 3 (routine assessment of patient index data 3)
timeFrame: Day 0
measure: RAPID 3 (routine assessment of patient index data 3)
timeFrame: 3 months
measure: RAPID 3 (routine assessment of patient index data 3)
timeFrame: 6 months
measure: HAQ scores
timeFrame: Day 0
measure: HAQ scores
timeFrame: 3 months
measure: HAQ scores
timeFrame: 6 months
Other outcomes:
Locations:
city: Strasbourg
country: France
facility: University Hospital, Strasbourg, France
state: Alsace
Study officials:
affiliation: University Hospital, Strasbourg, France
name: Jacques-Eric GOTTENBERG, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: