Heart Failure with Preserved Ejection Fraction, HFPEF MedDRA version: 20.1 Level: LLT Classification code 10076396 Term: Heart failure with preserved ejection fraction System Organ Class: 100000004849
Conditions
Interventions
Trade Name: Spironolaktion Pfizer
Spironolakton Orion
Spironolakton Takeda
Spironolakton Accord
Eplerenone Sandoz
Eplerenone Accord
Eplerenone Bluefish
Eplerenone Teva
Eplerenone Krka
Eplerenon Medica
Sponsors
Uppsala Clinical Research center
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Written informed consent 2. Age =50 years 3. Stable heart failure defined by symptoms and signs of heart failure as judged by local Investigator. Patients may be enrolled as an outpatient or at or close to the time of hospital discharge 4. Most recent left ventricular ejection fraction (LVEF) =40% 5. Elevated natriuretic peptide levels as defined by any of the following: a. most recent NT-proBNP >300 ng/L (or BNP >100 pg/mL) in sinus rhythm (at time of blood sampling); adjustments may be made for BMI according to table 3. b. most recent NT-proBNP >750 ng/L (or BNP >250 pg/mL) in atrial fibrillation (at time of blood sampling); adjustments may be made for BMI according to table 3. c. NT-proBNP >1200 ng/L (or BNP >400 pg/mL) within the last 12 months even if most recent value is lower 6. Regular use of loop diuretics, defined as daily or most days of the week 7. NYHA Class II-IV Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 2000 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 2000
Exclusion criteria
Exclusion criteria: 1. Previously enrolled in this study 2. Known EF 160 8. K >5.0 mmol/L 9. eGFR by MDRD < 30 ml/min/1.73m2 10. Current dialysis 11.Current lithium use 12. Actual or potential for pregnancy 13. Participation in another clinical trial where a mineralcorticoid receptor antagonist is studied. Co-enrollment in trials and observational studies of other medical and device interventions is permitted 14. Not suitable in the opinion of the Investigator due to severe or terminal comorbidity with poor prognosis, or characteristics that may interfere with adherence to trial protocol
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is to assess whether the initiation of spironolactone or eplerenone plus standard of care compared to standard of care alone reduces the incidence rate for total heart failure (HF) hospitalizations or cardiovascular (CV) death in HFpEF, studied with the pragmatic Registry-based Randomized Clinical Trial (RRCT) methodology. ;Secondary Objective: The secondary efficacy objectives are to evaluate: 1. Time to CV death or first HF hospitalization 2. Time to CV death 3. Incidence rate for total HF hospitalizations 4. Time to HF hospitalization 5. Time to all-cause mortality 6. Incidence rate for total all-cause hospitalizations 7. Time to all-cause hospitalization 8. Incidence rate for all-cause hospitalization or all-cause mortality Exploratory efficacy objectives are to evaluate: 1. Time to sudden death or aborted cardiac arrest 2. Time to acute coronary syndrome/acute myocardial infarction 3. Time to stroke 4. Time to hospitalization for hypokalemia 5. Time to new-onset atrial fibrillation (Sweden only) 6. Time to new-onset diabetes mellitus (Sweden only) Safety objectives are to evaluate changes in potassium and renal function Adherence will be evaluated by assessing time to cross-over (from spironolactone/ eplerenone to control and from control to spironolactone/ eplerenone);Primary end point(s): Time to CV death or first HF hospitalization;Timepoint(s) of evaluation of this end point: Evaluation of the primary endpoint will be performed at study end | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary • Time to CV death • Incidence rate for total HF hospitalizations or cardiovascular death • Incidence rate for total HF hospitalizations • Time to HF hospitalization • Time to all-cause mortality • Incidence rate for total all-cause hospitalizations • Time to all-cause hospitalization • Incidence rate for all-cause hospitalization or all-cause mortality Exploratory • Time to sudden death or aborted cardiac arrest • Time to acute coronary syndrome/acute myocardial infarction • Time to stroke • Time to hospitalization for hypokalemia • Time to new-onset atrial fibrillation (Sweden only) • Time to new-onset diabetes mellitus (Sweden only) • Incidence rate for total HF events, HF hospitalizations, or CV death • Incidence rate for unplanned non-hospitalized heart failure events • Time to unplanned non-hospitalized heart failure event • Incidence rate for total escalation of loop diuretic therapy, HF events, HF hospitalizations, or CV death • Incidence rate for escalation of loop diuretic therapy • Time to escalation of loop diuretic therapy Safety The following changes in potassium and renal function will be assessed by laboratory evaluations and acted upon by local investigators • Moderate hyperkalemia (K>5.5 mmol/L) • Severe hyperkalemia (K>6.0 mmol/L) • Moderate renal impairment: eGFR <30 mL/min/1.73 m2 • Severe renal impairment: eGFR <20 mL/min/1.73 m2 • Doubling of creatinine from baseline • Increase in K by more than 1.0 mmol/L from baseline • Levels of eGFR as continuous variable during follow-up • Levels of K as continuous variable during follow-up Events listed below will be collected centrally in both Sweden and the US at the end of the study • Time to hospitalization for hyperkalemia • Time to new onset hyperkalemia (outpatient encounters will be collected in Sweden only) • Time to dialysis • Time to hospitalization for renal failure • Time to new onset renal failure (outpatient encounters will be collected in Sweden | — |
Countries
Sweden, United States
Contacts
Public ContactMirjam Goedkoop Project manager
Uppsala Clinical Reseach center
Outcome results
None listed