Heart Failure (i.e. Heart Failure with mid-range/ moderately reduced ejection fraction (LVEF 40- 49 %) or with preserved ejection fraction (LVEF = 50 %) with evidence of impaired left ventricular filling capabilities)/ HFmrEF and HFpEF
Conditions
Interventions
Trade Name: Aldactone 25
Product Name: Spironolactone
Pharmaceutical Form: Tablet
INN or Proposed INN: spironolactone
CAS Number: 52-01-7
Other descriptive name: SPIRONOLACTONE
Concentration unit: mg
Sponsors
Charité Universitätsmedizin Berlin
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patients eligible for inclusion in this study have to fulfill all of the following 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) 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 =65 years) yes F.1.3.1 Number of subjects for this age range 866
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 160 µmol/ml) 4. History of anuria or acute renal failure (as defined by the KDIGO 2012 criteria for AKI) 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: 10. Evidence of right sided HF in the absence of left-sided structural heart disease 11. Specific etiologies such as infiltrative, genetic hypertrophic cardiomyopathy, pericardial constriction, sarcoidosis, amyloidosis and any other storage diseases 12. Clinically significant congenital heart disease underlying heart failure 13. Life-threatening or uncontrolled dysrhythmia, including symptomatic or sustained ventricular tachycardia and uncontrolled persistent or permanent atrial fibrillation (AF) or flutter (with a heart rate > 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 Medicinal Product (IMP) or placebo 19. Present use of any aldosterone antagonist or potassium sparing diuretics at the time of enrollment. (Consider stopping these potassium sparing drugs if clinically possible and upon discussion with the patient) 20. Required treatment with prohibited Co-medications according to the summary of product characteristics with the exception of ACE inhibitors or angiotensin receptor blockers. Potassium chloride must be used with cauti
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of the SPIRIT-HF study is to compare Spironolactone to Placebo in reducing the rate of the composite endpoint of recurrent heart failure hospitalizations and cardiovascular (CV) death in symptomatic HF patients (NYHA II-IV) with mid-range (LVEF 40- 49 %) or preserved (LVEF = 50 %) ejection fraction.;Secondary Objective: •To compare Spironolactone to placebo in reducing the recurrent rate of heart failure hospitalizations from any cause •To compare Spironolactone to placebo in reducing the rate of recurrent non-fatal hospitalizations from cardiovascular (CV) cause (i.e. hospitalization for non-fatal MI, non-fatal stroke, or the management of heart failure) •To compare Spironolactone to placebo in reducing the recurrent rate of hospitalizations from any cause •To compare Spironolactone to placebo in reducing the rate of death from cardiovascular (CV) cause •To compare Spironolactone to placebo in reducing the rate of death from any cause ;Primary end point(s): A composite of death from cardiovascular cause or recurrent heart failure hospitalizations over follow-up time from randomization.;Timepoint(s) of evaluation of this end point: death from cardiovascular cause or recurrent heart failure hospitalizations | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • To compare Spironolactone to placebo in reducing the recurrent rate of heart failure hospitalizations • To compare Spironolactone to placebo in reducing the rate of recurrent non-fatal hospitalizations from cardiovascular (CV) cause (i.e. hospitalization for non-fatal MI, non-fatal stroke, or the management of heart failure) • To compare Spironolactone to placebo in reducing the recurrent rate of hospitalizations from any cause • To compare Spironolactone to placebo in reducing the rate of death from cardiovascular (CV) cause • To compare Spironolactone to placebo in reducing the rate of death from any cause exploratory secondary endpoints: • To compare Spironolactone to placebo in reducing total non-fatal myocardial infarctions (MIs), and total non-fatal strokes • To compare Spironolactone to placebo in reducing left ventricular hypertrophy (measured by local ECG) • To compare Spironolactone to placebo on changes in the clinical summary score for HF symptoms, physical limitations and mental dimensions of quality of life (as assessed by the KCCQ, SF-36) • To compare Spironolactone to placebo in improving NYHA functional classification • To compare Spironolactone to placebo in increasing the time to develop new onset atrial fibrillation (NOAF) in patients with no history of AF and without AF on ECG during VR • To compare Spironolactone to placebo in reducing CV deats and total worsening HF events. A subject will be defined as having a CV death or worsening HF event when the subject has: 1. CV death or 2. a hospitalization for HF or 3. receives intravenous (IV) decongestive therapy (IV diuretics, IV neseritide or other natriuretic peptide, IV inotropes, and IV nitroglycerin [NTG]), and does not result in formal inpatient hospital admission, regardless of the setting (i.e. in an emergency room (ER) setting, in the physician’s office, an outpatient treatment facility, etc.). ;Timepoint(s) of evaluation of this end point: The analysis of the se | — |
Countries
Austria, France, Germany, Netherlands
Contacts
Public ContactMedizinische Klinik m.S Kardiologie
Charité Universitätsmedizin Berlin
Outcome results
None listed