SPironolactONe for the Maintenance of Sinus Rhythm in Patients With Atrial Fibrillation

NCT06204640 | Not Yet Recruiting Phase 3

• 1 other identifier: SPONSoR
• Study Type: interventional
• Target: 580
• Locations: 0 countries
• Sites: N/A

Brief Summary

Introduction: There is evidence that aldosterone and the activation of its receptor, mineralocorticoid receptor (MR), promote cardiac fibrosis and electrical disturbances. clinical data suggest that MRAs could have positive effects on AF burden, but some inconsistent results have been reported. Therefore, investigators propose to perform a randomized, multicenter, open blinded end-point (PROBE) study to evaluate the efficacy of spironolactone on AF recurrence in hypertensive patients with preserved LVEF. Materials and methods: SPONSoR trial will be a multicenter, landmark, randomized, open blinded end-point (PROBE) trial of the MRA, spironolactone, in 580 hypertensive patients referred for AF with preserved LVEF. 580 patients will be randomized in a 1:1 ratio to either receive oral spironolactone once daily on top of standard therapy or standard therapy alone, started the day of randomization and continued for 12 months. Spironolactone will be start at 25 mg per day initially then titrated to a maximum of 50 mg per day in the absence of contraindication at the 1-month study visit. AF detection will be provided by the use of a wearable optical photoplethysmography (PPG) device (ScanWatch 42mm®, Withings) throughout the duration of the study. These wearables optical PPG devices (ScanWatch 42mm®, Withings). The trial duration is 3 years (24 months for inclusion with 12 months of follow-up; total duration participation for the patient of 12 months).

Conditions

Atrial Fibrillation Recurrent

Outcome Measures

Primary Outcomes (1)

• AF recurrence

  First documented recurrence of AF occurring from randomization and within 12 months, defined as an episode lasting for at least 30 sec documented on 12-leads ECG (planned or not) or on a wearable optical photoplethysmography (PPG) device (ScanWatch 42mm®, Withings).

  from randomization and within12 months

Secondary Outcomes (8)

• symptomatic AF recurrence

  from randomization and within12 months

• delay of AF recurrence

  from randomization and within12 months

• AF burden

  from randomization and within12 months

• MACE

  from randomization and within12 months

• cerebral/systemic thrombo-embolic and bleeding event

  from randomization and within12 months

Study Arms (2)

spironolactone

EXPERIMENTAL

Drug: Spironolactone

standard of care

NO INTERVENTION

Interventions

Spironolactone DRUG

Spironolactone will be start at 25 mg per day initially then titrated to a maximum of 50 mg per day in the absence of contraindication at the 1-month study visit.

spironolactone

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age \> 18 years
• Hypertension defined as current use of anti-hypertensive drugs for more than 12 months
• Paroxysmal or no long-standing persistent AF (as defined by the ESC guidelines) with at least 1 episode within the preceding 6 months
• Sinus rhythm at enrolment
• Patient signed consent
• Willing to comply with scheduled visits, as outlined in the protocol
• French speaking
• Recipients of the social security regime

You may not qualify if:

• Contraindications to spironolactone therapy: pregnancy, breastfeeding, intolerance, hyperkalemia (\>5.0 mmol/L), severe renal dysfunction (defined as an estimated glomerular filtration rate (eGFR) \< 30 ml/min/1,73m² (per the CKD-EPI equation). Subjects with serum creatinine ≥2.5 mg/dl are also excluded even if their eGFR is ≥30 ml/min/1,73m²), Severe liver dysfunction.
• Patients already treated by other potassium sparing medication (amiloride, triamterene) or MRA (spironolactone, eplerenone, potassium canreonate, finerenone).
• Other MRAs indication: aldosteronism, heart failure, cirrhosis ascites, nephrotic syndrome, myasthenia
• LVEF \< 40% obtained within 6 months prior to V0
• Planned atrial fibrillation ablation within 6 months after randomization
• Moderate-to-severe valvular heart disease
• Permanent AF or long-standing persistent AF as defined by the ESC guidelines
• Previous left atrial ablation or previous maze or maze-like surgery
• Acute, reversible or secondary AF (infection, hyperthyroidism, pericarditis or myocarditis)
• Left atrium diameter \> 60 mm obtained within 6 months prior to V0
• Contraindication to oral anticoagulation therapy
• Patients with persistent bradycardia of less than 50 beats per minute, a PR interval of 0.2 second or more on ECG, second degree (or higher) atrioventricular block, and snus-node disease without an implanted pacemaker
• Hemodynamic instability and unstable conditions: angina or acute coronary syndrome or heart failure during the last 3 months, cardiogenic shock
• A life expectancy of 1 years or less
• Patients included or planning to be included in another medical research protocol whose pharmacological and scientific rationales might interfere with the Sponsor trial

Sponsors & Collaborators

• University Hospital, Caen: lead

MeSH Terms

Interventions

Spironolactone

Intervention Hierarchy (Ancestors)

Lactones; Organic Chemicals; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Central Study Contacts

Joachim Alexandre, MD, PhD

CONTACT

+330231063106; alexandre-j@chu-caen.fr

Dorothée Balayn

CONTACT

+330231063106; balayn-d@chu-caen.fr

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 13, 2023
• First Posted: January 12, 2024
• Study Start: March 1, 2024
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): January 1, 2029
• Last Updated: January 12, 2024

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: After publication of the SPONSOR study