Previous studies have shown that patients with heart failure with reduced pumping function and preserved kidney function experience improved symptoms, longer survival, and fewer hospitalizations when treated with medications such as eplerenone. However, individuals with impaired kidney function have been excluded from these trials due to concerns about potential adverse effects on potassium levels, kidney function, and possibly also blood pressure. As a result, clear treatment recommendations for this high-risk group are lacking. In recent years, however, background therapies have been modernized and are now associated with a lower risk of potassium disturbances. Preliminary data also suggest that patients with impaired kidney function may benefit from eplerenone treatment. However, confirmation through dedicated studies is needed. The primary objective of this pilot trial is to assess the feasibility and safety of eplerenone in patients with heart failure with reduced pumping function and impaired kidney function. Treatment effectiveness will also be explored.
Virtually all major trials in heart failure with reduced ejection fraction (HFrEF), including those investigating mineralocorticoid receptor antagonists (MRAs) such as eplerenone, have excluded patients with severe chronic kidney disease (CKD). This exclusion has likely been driven by concerns over the risks of hyperkalemia and worsening renal function (WRF). However, post-hoc analyses of these major trials, along with data from registries and cohort studies, suggest that patients with more advanced renal impairment may still derive an overall benefit from MRA treatment. The objective of this pilot trial is to evaluate the feasibility and safety of eplerenone in patients with HFrEF and severe CKD. An exploratory analysis of efficacy will also be performed.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
40
Participants will receive eplerenone 25 mg once daily or every other day, based on baseline potassium levels, eGFR, systolic blood pressure, and concomitant use of weak or moderate CYP3A4 inhibitors. The study will implement a safety protocol with predefined procedures for managing significant hyperkalemia, worsening renal function, and hypotension. These will include temporary or permanent dose reduction or discontinuation of eplerenone, and, if necessary, administration of the potassium binder sodium zirconium cyclosilicate (SZC, Lokelma®).
Department of Cardiology, Danderyd Hospital, Karolinska Institutet
Stockholm, Sweden
The primary endpoint is the proportion of participants who complete the treatment period with and without the need to use a potassium binder
Without eplerenone interruption/discontinuation due to safety reasons, with and without SZC
Time frame: Between the first and final day of the 12-week eplerenone treatment period
The occurrence of plasma potassium (P-K) ≥ 5.6 and ≥ 6.0
Yes/no
Time frame: Between the first and final day of each of the three 12-week study periods
Hospitalization for hyperkalemia
Primary or co-primary reason, yes/no
Time frame: Between the first and final day of each of the three 12-week study periods
The occurrence of P-K < 3.0
Yes/no
Time frame: Between the first and final day of each of the three 12-week study periods
Hospitalization for hypokalemia
Primary or co-primary reason, yes/no
Time frame: Between the first and final day of each of the three 12-week study periods
Decrease in eGFR of ≥ 30% and ≥ 50%
According to the revised Lund-Malmö method in ml/min/1.73 m2, compared to the start of each study period, yes/no
Time frame: Between the first and final day of each of the three 12-week study periods
Hospitalization for renal failure
Primary or co-primary reason, yes/no
Time frame: Between the first and final day of each of the three 12-week study periods
Initiation of dialysis
Yes/no
Time frame: Between the first and final day of each of the three 12-week study periods
Participant-reported lightheadedness due to orthostatic hypotension as judged by the investigator
Yes/no
Time frame: Between the first and final day of each of the three 12-week study periods
Participant-reported syncope
Yes/no
Time frame: Between the first and final day of each of the three 12-week study periods
Any participant-reported side effect
Yes/No
Time frame: Between the first and final day of each of the three 12-week study periods
Hospitalization for heart failure
Primary or co-primary reason, yes/no
Time frame: Between the first and final day of each of the three 12-week study periods
All-cause hospitalization
Yes/no
Time frame: Between the first and final day of each of the three 12-week study periods
Cardiovascular death
Primary reason, yes/no
Time frame: Between the first and final day of each of the three 12-week study periods
All-cause death
Yes/no
Time frame: Between the first and final day of each of the three 12-week study periods
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.