A Multicenter, Prospective, Randomized, Double-Blind, Placebo-Controlled Trial of Spironolactone for the Treatment of Active Rheumatoid Arthritis (Ra)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Les Hopitaux Universitaires De Strasbourg

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Musculoskeletal Diseases [C05]

Trial duration

22 Jun 2022 → 24 Feb 2026

Decision date (initial)

2024-09-09

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2024-516884-10-00

EudraCT number

2021-003958-23

ClinicalTrials.gov

NCT05092984

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Prophylaxis

To assess the efficacy of spironolactone on rheumatoid arthritis activity at 3 months compared to placebo.

Secondary objectives 9

1. To assess the safety of spironolactone in patients with RA
2. To assess the impact of spironolactone on cardiac biomarkers in patients with RA
3. To assess the impact of spironolactone on cardiac parameters in patients with RA (optional for the site)
4. To assess the clinical disease activity index (CDAI)
5. To assess the efficacy of spironolactone on RA activity at 6 months
6. To assess the EULAR/ACR 2010 classification and the Boolean remission
7. To assess the change of concomitant treatments
8. To assess the adhesion to the experimental treatment
9. To assess the evolution of the patient reported outcomes

Conditions and MedDRA coding

RHEUMATOID ARTHRITIS

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. patients 18 years of age and over
2. diagnosis of rheumatoid arthritis (RA) according to EULAR/ACR 2010 classification criteria
3. active RA: DAS28-CRP ≥ 3.2
4. insufficient response despite a stable DMARD treatment (cDMARD/tsDMARD/bDMARD) ≥ 12 weeks
5. stable dose of corticosteroid for at least 4 weeks prior to inclusion
6. 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
7. patient having been informed about the results of the preliminary medical visit
8. If woman of childbearing, she should have no desire to procreate for the duration of her 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
9. affiliation to a social security regime

Exclusion criteria 15

1. severe or acute renal insufficiency, defined by eGFR < 30mL/min
2. hyperkalemia, with K+ > 5,1 mmol/L
3. end-stage liver failure, cirrhosis
4. hypersensitivity to the active ingredients or intolerance to any of the excipients including lactose
5. Addison's disease
6. patient currently being treated with spironolactone, or previous spironolactone treatment in the last 3 months
7. concomitant treatment with: - mitotane, - other potassium-sparing diuretics (alone or in combination) such as amiloride, potassium canrenoate, eplerenone, triamterene
8. other inflammatory arthritis except associated Sjögren's syndrome
9. pregnancy (women of childbearing potential : positive blood pregnancy test at the inclusion visit (V0))
10. breastfeeding
11. 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
12. unwillingness or incapacity to adhere to study protocol (language barriers, cognitive disorders, etc.)
13. subjects who are compulsorily detained for treatment of either a psychiatric or physical (e.g., infectious disease) illness
14. patient who cannot be followed for 6 months
15. patient over the age of legal majority who are protected, or deprived of liberty by judicial or administrative decision (vulnerable subjects)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Proportion of patients achieving DAS28-CRP < 3,2, comparison between spironolactone and placebo arms

Secondary endpoints 9

1. Adverse events / Serious adverse events rate in each arm
2. NT-proBNP level
3. Cardiac parameters : QRS duration (ms); left ventricular end-diastolic volume index (mL/m2), left ventricular ejection fraction (%); left ventricular mass index (g/m2); left atrial volume index (mL/m2); early mitral flow; velocity (E) (m/s); late (atrial) mitral flow velocity (A) (m/s); E/A ratio; E/ early diastolic tissue velocity (e'); tricuspid annular plane systolic excursion
4. CDAI score
5. Proportion of patients achieving DAS28-CRP < 3,2 at 6 months
6. EULAR/ACR 20, 50, 70 2010 classification score and Boolean remission score at 3 and 6 months
7. Concomitant treatment modification
8. Treatment account (treatment boxes and patient diary)
9. RAPID 3 and HAQ scores

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Les Hopitaux Universitaires De Strasbourg

Sponsor organisation

Les Hopitaux Universitaires De Strasbourg

Address

1 Place De L Hopital, Cs 80426 Cs 80426

City

Strasbourg Cedex

Postcode

67091

Country

France

Scientific contact point

Organisation

Les Hopitaux Universitaires De Strasbourg

Contact name

Jacques-Eric GOTTENBERG

Public contact point

Organisation

Les Hopitaux Universitaires De Strasbourg

Contact name

Jacques-Eric GOTTENBERG

Locations

2 EU/EEA countries · 4 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 7 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications