Heart failure with preserved or mid-range ejection fraction HFmrEF and HFpEF
Conditions
Interventions
During the trial patients take one tablet of spironolactone of placebo
once-daily.
Sponsors
Charité Universitätsmedizin Berlin
Eligibility
Age
18 Years to 64 Years
Inclusion criteria
Inclusion criteria: 1. Written informed consent 2. Male or female, age >= 50 years 3. Current symptoms of Heart Failure (NYHA >= II) on diuretic treatment (any) during VR 4. Symptom(s) of HF >= 30 days prior to VR 5. Left ventricular ejection fraction >= 40 % at screening measured by echocardiography or MRI and evidence of structural/ functional abnormalities (at least one of the following criteria): o LAVI > 34 ml/m2 o E/e*mean >= 13 o Mean e* (septal and lateral) = 115 g/m² (m) and >=95 g/m² (f) o Septal or posterior left ventricular wall thickness >= 1.1 cm o Elevated left ventricular end-diastolic pressure (LVEDP) >=16 mmHg as determined by invasive measurement o Elevated pulmonary capillary wedge pressure >=15 mmHg (resting) or >=25 mmHg (exercise) as determined by invasive measurement 6. Patients with at least 1 of the following: a. HF hospitalization (defined as HF listed as the major reason for hospitalization) within 12 months prior to Visit of Screening and NTproBNP >200 pg/ml for patients in SR or >600 pg/ml for patients in AF on screening visit ECG (only if NT* proBNP is not available: BNP > 50/160 pg/ml), OR b. NT*proBNP >300 pg/ml for patients in SR or >900 pg/ml for patients in AF on the screening visit ECG (only if NT*proBNP is not available: BNP > 80/ 250 pg/ml) (for entering the study a historical measurement of natriuretic peptides within the last 6 months is acceptable) 7. Serum potassium
Exclusion criteria
Exclusion criteria: 1. History of hyperkalemia (potassium level >= 5.5 mmol/L) within the past two weeks before VR 2. Hyponatremia (sodium level = 1,8 mg/dl (> 160 µmol/ml) 4. History of anuria or acute renal failure (as defined by the KDIGO 2012 criteria for AKI; see Appendix XVIII.3) within the past two weeks before VR 5. Systolic blood pressure(SBP) >=160 mmHg if not on treatment with >=3 blood pressure lowering medications or >=180 mmHg irrespective of treatments, on 3 consecutive measurements at least 2-minute apart, at screening or at randomization 6. Acute coronary syndrome (including MI), urgent and elective percutaneous coronary intervention (PCI) within 30 days prior to VR. This does not include atrial or ventricular ablations, implantations of pacemakers or event recorders and peripheral percutaneous interventions due to peripheral artery disease. 7. Cardiac surgery and other major CV surgery, within the 3 months prior to VR. This includes percutaneous interventions, such as TAVR, mitral and tricuspid valve clipping or percutaneous reconstruction. 8. Current acute decompensated HF requiring augmented therapy with i.v. diuretics, i.v. vasodilators and/or i.v. inotropic drugs. Patients are eligible after initial stabilization 9. Probable alternative diagnoses that in the opinion of the investigator could account for the patient*s HF symptoms (i.e., dyspnea, fatigue) such as significant pulmonary disease (including primary pulmonary HTN) or anemia. Specifically, patients with the following are not eligible for randomization: a. Severe pulmonary disease including chronic obstructive pulmonary disease or severe asthma bronchiale or b. anemia (hemoglobin 100 beats per minute (bpm), RACE II) during VR. If AF with HR > 100/min, the patient may be rescreened after treatment for rate control 14. Presence of significant (i.e., more than moderate) coronary and / or valvular heart disease expected to lead to surgery during the following 6 months after randomization in the investigators opinion. 15. Stroke, transient ischemic attack, within 3 months prior to VR 16. Patients with prior major organ transplant or intent to transplant (on transplant list) or with current ventricular assist device (VAD) therapy 17. Evidence of present bilateral renal artery stenosis 18. Known intolerance or history of hypersensitivity to the active substance (Spironolactone) or to any of the excipients of the Investigational Med
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| - Cardiovascular (CV) death - Recurrent Heart Failure (HF) hospitalizations | — |
Secondary
| Measure | Time frame |
|---|---|
| - Death from any Cause - Hospitalization for CV Cause - Hospitalization for any Cause - AEs and SAEs - Sitting systolic BP, sitting diastolic BP, and heart rate - Laboratory values (including monitoring for hyperkalemia, hypokalemia, hyponatre mia and renal dysfunction) - ECG changes - Gynecomastia surveillance - Total non*fatal myocardial infarction - Total non*fatal Stroke - Left Ventricular Hypertrophy (local ECG) - Quality of Life (KCCQ, SF*36) - Functional Status (NYHA class) - Time to new onset of atrial fibrillation (NOAF) in patients with no history of AF and without AF on ECG at VR - Worsening Heart Failure (WHF) | — |
Countries
Netherlands
Outcome results
None listed