Purpose:
Both heart failure and chronic kidney disease have significant deleterious effects on life span and quality of life. Nearly seven million Americans suffer from chronic heart failure, which has a prognosis as bad as colon cancer. Nearly 36 million Americans suffer from chronic kidney disease, with a diagnosis easy to make with a simple blood test to measure serum creatinine or urine test for albumin. Chronic kidney disease often has no symptoms and is often diagnosed when it has progressed to when dialysis treatment needs to be considered.
50% of patients with heart failure also suffer from chronic kidney disease, and 50% of patients with chronic kidney disease suffer from heart failure, and when one suffers from both conditions, outcomes are particularly bad. Patients afflicted with heart failure present with signs and symptoms, including shortness of breath with activity, a decrease in exercise tolerance, fatigue, and ankle swelling that are often attributed to other conditions such as asthma or COPD. Mineralocorticoid receptor antagonists (MRA) and sodium-glucose cotransporter (SGLT) inhibitors separately reduce the progression of heart failure and chronic kidney disease. Therefore, combined MRAs and SGLT inhibitors are expected to provide complementary and additive treatment benefits.
Mineralocorticoid receptor antagonists are an important standard of care therapy for heart failure with reduced and normal ejection fraction. Still, they are underused globally, especially in patients with chronic kidney disease, due to safety concerns of hyperkalemia. Currently approved MRAs, such as spironolactone and eplerenone, have been shown to increase the risk of hyperkalemia when compared with placebo. Balcinrenone is a selective mineralocorticoid receptor (MR) modulator that exhibits a differentiated mode of action when compared to approved MRAs. This differentiated mode of action is expected to maintain the treatment benefits while reducing the risk of hyperkalemia compared to approved MRAs.
Description:
This is a Phase III, international, multicenter, randomized, double-blind, event-driven study in patients with chronic heart failure (preserved and reduced ejection fraction) and impaired kidney function who had a recent heart failure event. The aim is to evaluate the effect of balcinrenone/dapagliflozin vs dapagliflozin, given once daily on top of standard-of-care treatments, on cardiovascular death and heart failure events. The estimated mean treatment period is approximately 20 months for a study participant, followed by a one-month follow-up period. In addition, this trial may help determine whether balcinrenone/dapagliflozin is superior to dapagliflozin in reducing the risk of death from any cause, end-stage kidney disease, and slowing the progression of kidney disease.
Key Eligibility Requirements:
(Please note: Additional eligibility requirements may be assessed at the time of study screening evaluation.)
- Documented diagnosis of symptomatic heart failure (HF)
- Having had a recent HF event, defined as either:
- Managed with standard-of-care therapy for HF and impaired kidney function
- Not taking an MRA for one of the following reasons:
- Mineralocorticoid receptor antagonist not indicated due to left ventricular ejection fraction of > 40%
- Mineralocorticoid receptor antagonists are not recommended or contraindicated due to low eGFR or poor kidney function
- History of adverse reaction/intolerance from approved mineralocorticoid receptor antagonist: Hyperkalemia, Worsening kidney function, hypotension, hormonal side effects (such as gynecomastia and erectile dysfunction)
- An eGFR ≥ 20 to < 60 mL/min/1.73 m2
- Serum or plasma potassium ≥ 3.5 mmol/L and ≤ 5.0 mmol/L at Visit 1
- An NT-proBNP level must be > 300 pg/mL or (> 600 pg/mL if concomitant atrial fibrillation or atrial flutter at visit)
- Contraceptive use by females should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies
Subjects will be excluded if:
- Systolic blood pressure < 100 mmHg
- Systolic blood pressure ≥ 160 mmHg if on treatment with < 3 blood pressure lowering medications or ≥ 180 mmHg irrespective of treatments
- Type 1 diabetes mellitus
- History of malignancy within the last 5 years, excluding successful treatment of basal or squamous cell skin carcinoma or in situ carcinoma of the cervix
- Treatment with an approved mineralocorticoid receptor antagonist for more than 7 days within the last month prior to randomization or planned treatment with a mineralocorticoid receptor antagonist
PARTICIPATION IN THIS TRIAL CAN BE UP TO 21 months
The information we are providing includes important background on a variety of important cardiovascular conditions and ongoing clinical trials. We encourage you to use this information in discussions with your health care professional. Since enrollment in clinical trials are limited in time, we can’t guarantee their availability at any given time. However, we have continued access to new clinical trial opportunities and will share them as soon as they are available.