Paroxysmal and persistent atrial fibrillation MedDRA version: 18.1 Level: LLT Classification code 10071667 Term: Persistent atrial fibrillation System Organ Class: 100000004849 MedDRA version: 18.1 Level: LLT Classification code 10066664 Term: Recurrent symptomatic atrial fibrillation System Organ Class: 100000004849 MedDRA version: 18.1 Level: LLT Classification code 10003661 Term: Atrial fibrillation paroxysmal System Organ Class: 100000004849
Conditions
Interventions
Trade Name: Spirix
Pharmaceutical Form: Tablet
INN or Proposed INN: spironolactone
Other descriptive name: SPIRONOLACTONE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration nu
Sponsors
Department of Medical Research, Odense University Hospital, Svendborg Hospital
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patients = 18 years of age, male or female. Signed written informed consent. Paroxysmal atrial fibrillation on one or more occasions, detected on 12-lead ECG or Holter monitoring with each AF-episode lasting = 30 seconds, within the last 12 months prior to the screening visit, or persistent AF on one or more occasions that has been direct current (DC) cardioverted within the last 12 months prior to the screening visit. Patients with CHA2DS2-VASc score = 1 will be encouraged to start anticoagulant treatment, but will not be excluded if there are reasonable reasons not to, i.e. risk of bleeding. Patients can choose between standard anticoagulation therapies, i.e. warfarin or non vitamin-K oral anticoagulants (NOAC) such as dabigatran, apixaban and rivaroxaban. Women with childbearing potency must use effective contraception (e.g. implants, hormonal depot injections, combined oral contraceptives, intra-uterine devices or vasectomized partner). Men enrolled in this study must agree to use adequate barrier birth control measures during the treatment period of the study. Reliable contraception should be maintained throughout the study and for 30 days after study drug discontinuation. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 90 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 40
Exclusion criteria
Exclusion criteria: Chronic atrial fibrillation. Previous radiofrequency ablation for atrial fibrillation or previous surgical treatment of atrial fibrillation, i.e. MAZE or His-ablation. Heart failure (New York Heart Association (NYHA) class = II and/or LVEF less than 40%). Severe coronary artery disease (acute myocardial infarction within 6 months prior to the screening visit, previous coronary artery bypass graft (CABG) or stabile angina pectoris (Canadian Cardiovascular Society (CCS) class =II). Stroke or transient ischemic cerebral attack within 6 months prior to the screening visit. Pregnant women or women of childbearing potential not on adequate birth control. Only women with a highly effective method of contraception (oral contraception, intra-uterine device or sterile women) can be randomized. Presence of severe and hemodynamically significant valvular heart disease. Any disease that limits life expectancy to less than 1 year. Hepatic insufficiens classified as Child-Pugh B or C. Participation in another clinical trial, either within the last 30 days or ongoing. Breastfeeding women. Ongoing therapy with class IC antiarrhythmics (flecainide, propafenone), amiodarone, dronedarone or sotalol. Chronic or acute kidney disease (estimated glomerular filtration rate (eGFR) = 45 ml/min/1,73m2 (4-variable MDRD equation)). Baseline serum potassium > 5,0 mmol/l. Intolerance or contradictions to spironolactone, i.e. latest product information on Spirix®. Intolerance or contradictions to dabigatran (Pradaxa®) i.e. latest product information. Patients who are noncompliant to the medical treatment. Atrial fibrillation that is associated with an acute reversible condition, i.e. heart surgery, untreated hyperthyroidism etc.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To investigate whether or not therapy with a mineralocorticoid receptor antagonist (MRA), in this case spironolactone, added to optimal medical treatment in normotensive or hypertensive patients with paroxysmal or persistent atrial fibrillation diminishes diffuse myocardial fibrosis in left atria and ventricle, atrial remodeling and thus improve left atrial function as compared with conventional treatment. ;Secondary Objective: To investigate whether or not add-on therapy with spironolactone reduces recurrent episodes of atrial fibrillation, health economics thus improves quality of life and decreses inflammatory and neurohumoral marksers in blood in patients with paroxysmal or persistent atrial fibrillation compared to usual care. ;Primary end point(s): 1. Myocardial extracellular volume (ECV) will be quantified as a surrogate for diffuse myocardial fibrosis in left atrium and ventricle by T1 mapping using modified look locker sequences (Siemens) and late gadolinium enhancement technique asserssed by cardiac magnetic resonanse (CMR). 2. Function and volume dynamics of left atrium and ventricle will be assessed with CMR and speckle tracking, strain and strain rate on 2-dimensional (2D) and 3-dimensional (3D) transthoracic echocardiography. ;Timepoint(s) of evaluation of this end point: 1. CMR will be assessed at the time of randomization and at 12 months. 2. Transthoracic echocardiography: both two (2D) and three dimensional (3D) images will be assessed at the time of randomization and at 6 and 12 months. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. The burden of atrial fibrillation will be assessed as cumulative burden of atrial fibrillation, registered on 12-lead ECG recordings and serial longterm Holter monitoring, where a recurrent episode of atrial fibrillation is defined as atrial fibrillation = 30 seconds of duration. Burden of atrial fibrillation will also include the total duration of atrial fibrillation, recorded on Holter monitoring. 2. Health economics, including total number of hospitalizations, hospitalizations related to atrial fibrillation and the total duration of hospitalizations in days. 3. Quality of life assessed with Short Form-12 (SF-12) questionnaire. 4. Inflammatory, neurohumoral and potential markers of atrial fibrosis measured in blood. The following efficacy biomarkers will be measured: high-sensitivity C-reactive protein (hs-CRP), Thyroid Stimulation Hormone (TSH), Interleukin-6 (IL6), N-terminal pro-brain natriuretic peptide (NT-proBNP), Atrial (A-type) natriuretic peptide (pro-ANP), renin, Procollagen III N-terminal propeptide and fibulin-1. Blood samples measurements for safety will include measurement of potassium, sodium, creatinine and BUN. ;Timepoint(s) of evaluation of this end point: 1. 7 days Holter monitoring will be performed at the time of randomization and at 6 and 12 months. 12-lead ECG will be performed at the time of randomization, at 1 week and subsequently at 1, 2,3,6,9 and 12 months. The study subjects patents will be encouraged to seek a doctor of choice in case of symptoms that might indicate recurrence of atrial fibrillation to assess a 12-lead ECG. 2. Data will be collected thorughtout 12 months of follow-up period. 3. SF-12 will be performed at baseline and at 12 months. 4. Blood samples: blood samples measurements for biomarkers will be collected at the time of randomization and at 6 and 12 months. Blood samples measurements for safety will be collected at baseline, 1 week and 1, 2,3,6,9 and 12 months. | — |
Countries
Denmark
Contacts
Public ContactDragana Rujic
Department of Medical Research, Odense University Hospital, Svendborg Hospital
Outcome results
None listed