SPironolactONe for the maintenance of Sinus Rhythm in hypertensive patients with atrial fibrillation and preserved left ventricular ejection fraction: a Prospective Randomized Open Blinded End-point (PROBE) multicenter study (SPONSoR study).

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centre Hospitalier Universitaire De Caen Normandie

Participant type

Patients

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Decision date (initial)

2024-10-24

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

CHU CAEN Normandie

External identifiers

EU CT number

2024-518146-25-00

EudraCT number

2020-005484-31

ClinicalTrials.gov

NCT06204640

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Therapy

To establish whether administration of spironolactone (25 mg per day initially, titrated to a maximum of 50 mg per day) on top of standard therapy, leads to a reduction in the recurrence of documented AF episodes (symptomatic or not) occurring from randomization and within 12 months, compared with standard therapy alone, in hypertensive patients with preserved LVEF.

Secondary objectives 8

1. Symptomatic documented AF occurring from randomization and within 12 months
2. The time of recurrence of the first documented AF episode (symptomatic or not), from randomization and within 12 months
3. The cumulative AF burden from randomization and within 12 months
4. Major cardiovascular events and death (all-cause mortality, stroke, myocardial infarction, heart failure) occurring from randomization and within 12 months
5. The rate of cerebral/systemic thrombo-embolic and bleeding events
6. Mean ventricular rate at the recurrence of AF
7. Blood pressure reduction and control
8. Safety parameters, particularly blood pressure, serum potassium levels and renal function from randomization and within 12 months

Conditions and MedDRA coding

patients with atrial fibrillation and preserved left ventricular ejection fraction

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. □ Male or female (since spironolactone is not recommended during pregnancy and breastfeeding, a highly sensitive pregnancy test (serum HCG) will be systematically carried out in women of childbearing age and information will be given to non-pregnant women at the time of inclusion to instruct them to use an effective method of contraception during all the study period. Effective methods include: combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation: oral, intravaginal, transdermal, or progestogen-only hormonal contraception associated with inhibition of ovulation: oral, injectable, implantable, or intrauterine device, or intrauterine hormone-releasing system, or bilateral tubal occlusion or vasectomised partner, or sexual abstinence)
2. □ Age ≥18 years
3. □ Hypertension defined as current use of anti-hypertensive drugs for more than 12 months
4. □ Paroxysmal or no long-standing persistent AF (as defined by the ESC guidelines) with at least 1 episode within the preceding 12 months
5. □ Sinus rhythm at enrolment
6. □ Patients with a smartphone (Android or iPhone)
7. □ Patient signed consent
8. □ Willing to comply with scheduled visits, as outlined in the protocol
9. □ French speaking
10. □ Recipients of the social security regime

Exclusion criteria 18

1. □ Contraindications to spironolactone therapy: pregnancy, breastfeeding, intolerance, hyperkalemia (≥ 5 mmol/L), severe renal dysfunction (defined as an estimated glomerular filtration rate (eGFR) < 50 ml/min/1,73m² (per the CKD-EPI equation). Severe liver dysfunction
2. □ Patients already treated by other potassium sparing medication (amiloride, triamterene) or MRA (spironolactone, eplerenone, potassium canreonate, finerenone)
3. □ Other MRAs indication: aldosteronism, heart failure, cirrhosis ascites, nephrotic syndrome, myasthenia
4. □ LVEF < 40% obtained within 6 months prior to V0
5. □ Planned atrial fibrillation ablation within 6 months after randomization
6. □ Moderate-to-severe valvular heart disease
7. □ Permanent AF or long-standing persistent AF as defined by the ESC guidelines
8. □ AF on the ECG at the inclusion visit
9. □ Previous left atrial ablation or previous maze or maze-like surgery
10. □ Acute, reversible or secondary AF (infection, hyperthyroidism, pericarditis or myocarditis)
11. □ Left atrium diameter > 60 mm obtained within 6 months prior to V0
12. □ Patients with persistent bradycardia of less than 50 beats per minute or a PR interval of 0.2 second or more on ECG, or second degree (or higher) atrioventricular block, or sinus-node disease without an implanted pacemaker
13. □ Hemodynamic instability and unstable conditions: angina or acute coronary syndrome or heart failure during the last 3 months, cardiogenic shock
14. □ A life expectancy of 1 years or less
15. □ Patients included or planning to be included in another medical research protocol whose pharmacological and scientific rationales might interfere with the Sponsor trial
16. □ Patients unable to complete the protocol follow-up
17. □ Pregnant or nursing women
18. □ Adults with protective measures (curatorship or tutorship) and vulnerable patients

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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)

Secondary endpoints 8

1. The recurrence of symptomatic documented AF episodes from randomization and within 12 months
2. The delay (days) of recurrence of the first documented AF episode (symptomatic or not) during the follow-up
3. The cumulative AF burden defined as the percentage of time in irregular rhythm on the wearable optical photoplethysmography (PPG) device (ScanWatch 42mm®, Withings) from randomization and within 12 months
4. Composite of major cardiovascular events and death (death from any cause, stroke, heart failure, myocardial infarction) occurring from randomization and within 12 months
5. Occurrence of cerebral/systemic thrombo-embolic and bleeding events
6. Mean ventricular rate (beats per minute) at the recurrence of AF on 12-leads ECG (planned or not) or on a wearable optical photoplethysmography (PPG) device (ScanWatch 42mm®, Withings)
7. Blood pressure-lowering efficacy evaluated on blood pressure measurements from randomization to 1, 6, and 12 months as assessed by office blood pressure
8. Safety endpoints: occurrence of low blood pressure, changes in serum potassium and acute kidney injury from randomization and within 12 months

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Hospitalier Universitaire De Caen Normandie

Sponsor organisation

Centre Hospitalier Universitaire De Caen Normandie

Address

Avenue De La Cote De Nacre, Cs 30001 Cs 30001

City

Caen Cedex 9

Postcode

14033

Country

France

Scientific contact point

Organisation

Centre Hospitalier Universitaire De Caen Normandie

Contact name

Coordinating investigator

Public contact point

Organisation

Centre Hospitalier Universitaire De Caen Normandie

Contact name

Coordinating investigator

Locations

1 EU/EEA country · 14 investigational sites

By country

Investigational sites

Results and documents

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

Documents 6 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