Elderly patients with Clinical and Biological risk factors for developing heart failure MedDRA version: 18.0 Level: SOC Classification code 10007541 Term: Cardiac disorders System Organ Class: 10007541 - Cardiac disorders
Conditions
Interventions
Trade Name: Spironolactone
Pharmaceutical Form: Tablet
Sponsors
ACS Biomarker
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Written informed consent will be obtained prior to any study procedure; 2. Age >65years 3. Clinical risk factors for developing heart failure, either: Coronary artery disease (h/o myocardial infarction, angioplasty or coronary artery bypass) Or B. At least two of the following: • Diabetes Mellitus requiring Hypoglycaemic Pharmacotherapy • Receiving pharmacological treatment for Hypertension • Microalbuminuria • Abnormal ECG (left ventricular hypertrophy, QRS >120msec, abnormal Q-waves) 4. Biological risk: NT-pro-BNP values between 125 and 1,000 ng/L or BNP values between 35 and 280 pg/ml (consistent with ESC guidelines indicating risk of HF but helping to rule out prevalent HF or atrial fibrillation which are associated with marked increases in NT-proBNP/BNP and should be investigated) Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 800
Exclusion criteria
Exclusion criteria: 1. Recent wound healing/inflammation: • Surgical procedure, coronary, cerebral or peripheral vascular events or infection in the prior 3 months • Cancer • Autoimmune disease • Hepatic Disease 2. Pre-existing diagnosis of clinical HF 3. Moderate/severe LV systolic ventricular dysfunction, i.e. LVEF 5.0 mmol/L 7. Treatment with an MRA or a loop diuretic (furosemide, bumetanide, ethacrynic acid or torasemide) in the previous three months 8. Potassium supplements or potassium-sparing diuretic at time of enrolment. 9. Atrial fibrillation within one month prior to inclusion (AF lasting <60 seconds on ambulatory ECG monitoring is permitted) 10. History of hypersensitivity to spironolactone. 11. Patients unable to give written informed consent. 12. Participation in another interventional trial in the preceding month 13. Ability to walk is, in the investigators opinion, clearly limited by joint disease or other locomotor problems rather than by cardiorespiratory fitness
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): Changes in serum concentrations of PIIINP from baseline to nine months. ;Timepoint(s) of evaluation of this end point: at 9 months compared to baseline;Main Objective: To investigate whether spironolactone can favourably alter extra-cellular matrix remodelling, assessed by changes in the fibrosis biomarker Procollagen Type III N-Terminal Peptide (PIIINP), in patients at increased risk of developing heart failure and whether this effect is greater in patients with increased plasma concentrations of Gal-3.; Secondary Objective: To investigate whether, over nine months. spironolactone can induce favourable changes in: serum or plasma concentrations of other biomarkers of extracellular matrix turnover, in cardiac remodelling, in vascular function , in exercise capacity and To investigate whether spironolactone alters the rate of the clinical composite of development of heart failure or atrial fibrillation, non-fatal myocardial infarction or stroke or CV death; or change pre-specified expected Adverse events | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1.Changes in levels of biomarkers of extracellular matrix turnover: PICP (synthesis) and ICTP (degradation). 2.Cardiac remodelling, assessed by echocardiography 3.Distance walked on a shuttle walk-test with assessment of peak heart and respiratory rate if data on shuttle test are available. . 4.Vascular function assessed by non-invasive technologies 5.Rate of the clinical composite of development of heart failure or atrial fibrillation, non-fatal myocardial infarction or stroke or CV death 6.Safety endpoints: Investigator reported adverse events (AEs) will be collected using the ad hoc reporting system. In addition, pre-specified expected AEs will be monitored : Worsening renal function (decline in eGFR >20%), Hyperkalemia (rise of serum potassium to >5.5 mmol/L), Rate of gynaecomastia and/or breast pain, Changes in serum potassium and eGFR, 4.5 Hypotension, falls and fractures ;Timepoint(s) of evaluation of this end point: at 9 months compared to Baseline and more specifically for safety : at all visits | — |
Countries
Germany, Ireland, Netherlands, United Kingdom
Contacts
Public ContactSylvia Van Haren
ACS Biomarker
Outcome results
None listed