SPIRonolactone In the Treatment of Heart Failure - A double-blind, randomized, placebo-controlled, parallel group, interventional phase III study to evaluate the efficacy and safety of spironolactone compared to placebo on the composite endpoint of recurrent heart failure hospitalizations and cardiovascular death in patients with heart failure with mid- range or preserved ejection fractio

Phase 3

Recruiting

Conditions: Heart failure with preserved or mid-range ejection fraction
HFmrEF and HFpEF
10019280

Registration Number: NL-OMON54576

Lead Sponsor: Charité Universitätsmedizin Berlin

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Recruiting

Sex: Not specified

Target Recruitment: 100

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) < 9 cm/s
o Left ventricular mass index (LVMI) >= 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 < 5.2 mmol/L prior to randomization

Exclusion Criteria

1. History of hyperkalemia (potassium level >= 5.5 mmol/L) within the past two
weeks before
VR
2. Hyponatremia (sodium level < 135 mmol/L) prior to randomization
3. Severe renal dysfunction, defined as an estimated glomerular filtration rate
of less than 30
mL/min/1.73m2) as calculated by the CKD EPI 2009 formula at VScr/VR or serum
creatinine
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 < 10 g/dL males and < 9.5 g/dL females)
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 Med

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>- Cardiovascular (CV) death <br /><br>- Recurrent Heart Failure (HF) hospitalizations </p><br>

Secondary Outcome Measures

Name	Time	Method
<p>- Death from any Cause <br /><br>- Hospitalization for CV Cause <br /><br>- Hospitalization for any Cause <br /><br>- AEs and SAEs <br /><br>- Sitting systolic BP, sitting diastolic BP, and heart rate <br /><br>-<br /><br>Laboratory values (including monitoring for hyperkalemia, hypokalemia, hyponatre<br /><br>mia and renal dysfunction) <br /><br>- ECG changes <br /><br>- Gynecomastia surveillance <br /><br>- Total nonfatal myocardial infarction <br /><br>- Total nonfatal Stroke <br /><br>- Left Ventricular Hypertrophy (local ECG) <br /><br>- Quality of Life (KCCQ, SF*36) <br /><br>- Functional Status (NYHA class) <br /><br>- Time to new onset of atrial fibrillation (NOAF) in patients with no <br /><br>history of AF and without AF on ECG at VR <br /><br>- Worsening Heart Failure (WHF) </p><br>