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

Rheumatoid Arthritis Clinical Trial

— ALDORA  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05092984
• Other study ID #: 8154
• Secondary ID: 2021-003958-23
• Status: Recruiting
• Phase: Phase 3
• Start date: June 22, 2022
• Est. completion date: March 2024

Study information

• Verified date: December 2022
• Source: University Hospital, Strasbourg, France
• Contact: Jacques-Eric GOTTENBERG, Professor
• Phone: 3 88 12 79 53
• Email: jacques-eric.gottenberg[@]chru-strasbourg.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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)

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 154
• Est. completion date: March 2024
• Est. primary completion date: March 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

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.
• 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.

Locations

Country	Name	City	State
France	University Hospital, Strasbourg, France	Strasbourg	Alsace

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Strasbourg, France

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Adverse events / Serious adverse events rate in each arm		6 months
Secondary	NT-proBNP level	Test for B-type natriuretic peptide (BNP), used for heart failure evaluation.	Day 0
Secondary	NT-proBNP level	Test for B-type natriuretic peptide (BNP), used for heart failure evaluation.	3 months
Secondary	NT-proBNP level	Test for B-type natriuretic peptide (BNP), used for heart failure evaluation.	6 months
Secondary	Cardiac parameters: QRS duration (ms)	QRS duration (ms);	Day 0
Secondary	Cardiac parameters: left ventricular end-diastolic volume index (mL/m2)	left ventricular end-diastolic volume index (mL/m2),	Day 0
Secondary	Cardiac parameters: left ventricular ejection fraction (%)	left ventricular ejection fraction (%);	Day 0
Secondary	Cardiac parameters: left ventricular mass index (g/m2)	left ventricular mass index (g/m2);	Day 0
Secondary	Cardiac parameters: left atrial volume index (mL/m2)	left atrial volume index (mL/m2);	Day 0
Secondary	Cardiac parameters: early mitral flow	early mitral flow;	Day 0
Secondary	Cardiac parameters: velocity (E) (m/s)	velocity (E) (m/s);	Day 0
Secondary	Cardiac parameters: late (atrial) mitral flow velocity (A) (m/s)	late (atrial) mitral flow velocity (A) (m/s);	Day 0
Secondary	Cardiac parameters: E/A ratio	E/A ratio;	Day 0
Secondary	Cardiac parameters: E/ early diastolic tissue velocity (e')	E/ early diastolic tissue velocity (e');	Day 0
Secondary	Cardiac parameters: tricuspid annular plane systolic excursion	tricuspid annular plane systolic excursion	Day 0
Secondary	Cardiac parameters: QRS duration (ms)	QRS duration (ms);	3 months
Secondary	Cardiac parameters: left ventricular end-diastolic volume index (mL/m2)	left ventricular end-diastolic volume index (mL/m2),	3 months
Secondary	Cardiac parameters: left ventricular ejection fraction (%)	left ventricular ejection fraction (%);	3 months
Secondary	Cardiac parameters: left ventricular mass index (g/m2)	left ventricular mass index (g/m2)	3 months
Secondary	Cardiac parameters: left atrial volume index (mL/m2)	left atrial volume index (mL/m2);	3 months
Secondary	Cardiac parameters: early mitral flow	early mitral flow;	3 months
Secondary	Cardiac parameters: velocity (E) (m/s)	velocity (E) (m/s);	3 months
Secondary	Cardiac parameters: late (atrial) mitral flow velocity (A) (m/s)	late (atrial) mitral flow velocity (A) (m/s);	3 months
Secondary	Cardiac parameters: E/A ratio	E/A ratio;	3 months
Secondary	Cardiac parameters: E/ early diastolic tissue velocity (e')	E/ early diastolic tissue velocity (e')	3 months
Secondary	Cardiac parameters: tricuspid annular plane systolic excursion	tricuspid annular plane systolic excursion	3 months
Secondary	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	Day 0
Secondary	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	3 months
Secondary	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	6 months
Secondary	Proportion of patients achieving DAS28-CRP < 3.2		6 months
Secondary	EULAR/ACR 20 2010 classification score	American College of Rheumatology 20/50/70 criteria	3 months
Secondary	EULAR/ACR 50 2010 classification score	American College of Rheumatology 20/50/70 criteria	3 months
Secondary	EULAR/ACR 70 2010 classification score	American College of Rheumatology 20/50/70 criteria	3 months
Secondary	Boolean remission score		3 months
Secondary	EULAR/ACR 20 2010 classification score	American College of Rheumatology 20/50/70 criteria	6 months
Secondary	EULAR/ACR 50 2010 classification score	American College of Rheumatology 20/50/70 criteria	6 months
Secondary	EULAR/ACR 70 2010 classification score	American College of Rheumatology 20/50/70 criteria	6 months
Secondary	Boolean remission score		6 months
Secondary	Concomitant treatment modification	Assess the change of concomitant treatments. In case of lack efficacy with clinical symptoms requiring the dosage modification of the current DMARD or the introduction of a new DMARD, the investigator is free to choose the best treatment for the patient. Nevertheless, DMARDs intensification due to worsening signs and symptoms of at any time of the trial will be considered as treatment failure.	3 months
Secondary	Concomitant treatment modification	Assess the change of concomitant treatments. In case of lack efficacy with clinical symptoms requiring the dosage modification of the current DMARD or the introduction of a new DMARD, the investigator is free to choose the best treatment for the patient. Nevertheless, DMARDs intensification due to worsening signs and symptoms of at any time of the trial will be considered as treatment failure.	6 months
Secondary	Treatment account (treatment boxes and patient diary)		3 months
Secondary	Treatment account (treatment boxes and patient diary)		6 months
Secondary	RAPID 3 (routine assessment of patient index data 3)	RAPID3 : Index to asses and monitor patients with RA	Day 0
Secondary	RAPID 3 (routine assessment of patient index data 3)	RAPID3 : Index to asses and monitor patients with RA	3 months
Secondary	RAPID 3 (routine assessment of patient index data 3)	RAPID3 : Index to asses and monitor patients with RA	6 months
Secondary	HAQ scores	HAQ : Health Assessment Questionnaire	Day 0
Secondary	HAQ scores	HAQ : Health Assessment Questionnaire	3 months
Secondary	HAQ scores	HAQ : Health Assessment Questionnaire	6 months