Inhibition of Aldosterone to Reduce Myocardial Diffuse Fibrosis in Patients With Paroxysmal and Persistent Atrial Fibrillation in Preventing Recurrent Episodes of Atrial Fibrillation (INSPIRE-AF)
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|ClinicalTrials.gov Identifier: NCT02764619|
Recruitment Status : Unknown
Verified May 2016 by Dragana Rujic, Svendborg Hospital.
Recruitment status was: Active, not recruiting
First Posted : May 6, 2016
Last Update Posted : May 17, 2016
|Condition or disease||Intervention/treatment||Phase|
|Atrial Fibrillation||Drug: Spironolactone Drug: Placebo||Phase 3|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||125 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||Phase 3, Prospective, Randomized, Double-blinded, Placebo-controlled Study to Evaluate Efficacy of add-on Therapy With Spironolactone to Reduce Diffuse Myocardial Fibrosis Thus Preventing Recurrent Episodes of Atrial Fibrillation in Patients With Paroxysmal or Persistent Atrial Fibrillation and Preserved Ejection Fraction Compared to Usual Care.|
|Study Start Date :||December 2013|
|Estimated Primary Completion Date :||February 2017|
|Estimated Study Completion Date :||April 2017|
Active Comparator: Aldo group
Fixed dose of spironolactone, Spirix (Takeda Pharma A/S), 25 mg once daily, added to optimal medical treatment (usual care) for atrial fibrillation.
Placebo Comparator: Control group
Matched placebo, 1 pill once daily, added to optimal medical treatment (usual care) for atrial fibrillation.
- Determine change (∆) in diffuse myocardial fibrosis between groups, assessed by cardiovascular magnetic resonance (CMR) T1 mapping. [ Time Frame: Change from baseline at 12 months ]The study aims to non-invasively quantify extracellular volume fraction (ECV) in left atrium and ventricle as surrogate marker of diffuse myocardial fibrosis. T1 relaxation times (T1 values) will be obtained from T1 mapping. T1 values are given in [ms]. Extracellular volume fraction (ECV) will be calculated using pre-contrast and post-contrast T1 values for myocardium and blood pool (using hematocrit) using following formula: ECV = (√T1 "myocardium post-contrast" - 1 / T1 "myocardium pre-contrast") (1 / T1 "blood post-contrast" - 1 / T1 "blood pre-contrast") x (1- hematocrit). ECV is given in percentage.
- Determine difference (α) in myocardial stiffness between groups, assessed by strain analysis. [ Time Frame: At time of randomization, 6 and 12 months ]The study aims to characterize longitudinal changes in imaging characteristics.Strain is a dimensionless quantity and is produced by application of stress. It represents the fractional or percentage change from the original or unstressed dimension and includes both lengthening, or expansion (positive strains) and shortening, or compression (negative strains). Strain rate is the temporal derivative of strain and is a measure of the rate of deformation, with units of [1/s]. The strain rate is also equivalent to the shortening velocity per fiber length.
- Determine difference (β) in left atrial phasic function between groups, assessed by transthoracic echocardiography. [ Time Frame: At time of randomization and 12 months ]Left atrial phasic function is measured by the volumetric method, where LA volumes are measured at different time points of the cardiac cycle. Left atrial volumes on time curves are indexed to body surface area and are given in [mL/m2]. Speckle tracking is a technique that is complementing phasic function measures with myocardial deformation. Quantitative curves are representing all segments showing wall deformation during the cardiac cycle.
- Arrhythmic composite endpoint. [ Time Frame: 12 months from randomization ]Burden of atrial fibrillation, where recurrent episodes of atrial fibrillation are documented with 12-lead ECG recordings and serial Holter monitoring. AF burden assessed as cumulative AF burden, registered on 12-lead ECG recordings and serial 48-hour Holter monitoring, where a recurrent episode of AF is defined as AF ≥ 30 seconds of duration. AF burden will also include the total duration of AF, recorded on Holter monitoring.
- Life quality, assessed by SF-12. [ Time Frame: At time of randomization and 12 months ]
- Determine level of collagen turnover between groups, measured in blood. [ Time Frame: At time of randomization, 6 and 12 months ]
The aims of the study are:
- To investigate whether or not the burden of diffuse myocardial fibrosis (T1 mapping) is associated with biomarkers measured in blood.
- To investigate whether or not left atrial volume and function is associated with biomarkers measured in blood.
Additional biomarkers may be included as the research in those fields progresses during the conduct of this clinical trial.
- Adverse events [ Time Frame: 15 months from randomization ]Adverse events (AE's) and serious adverse events (SAE's) of special interest that is hyperkalemia (serum potassium ≥ 5,5 mmol/l and serum potassium ≥ 6 mmol/l), worsening renal function (WRF) defined as a 30 % reduction in estimated glomerular filtration rate (eGFR) from baseline and gynecomastia ( Common Terminology Criteria for Adverse Events version 5.0, grade ≥ 1).
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02764619
|Department of Cardiovascular Research, Medical Department, Odense University Hospital, Svendborg|
|Svendborg, Region of Southern Denmark, Denmark, 5700|
|Study Director:||Kenneth Egstrup, Professor||Department of Cardiovascular Research, Medical Department, Odense University Hospital, Svendborg|
|Principal Investigator:||Dragana Rujic, MD, Ph.D.sc.||Department of Cardiovascular Research, Medical Department, Odense University Hospital, Svendborg|