A Phase III, Randomised, Double-blind Study to Evaluate the Effect of Balcinrenone/Dapagliflozin, Compared with Dapagliflozin, on the Risk of Heart Failure Events and Cardiovascular Death in Patients with Heart Failure and Impaired Kidney Function
Research Study on Heart Failure and Kidney Function
Wayne Gray
Primary Investigator
Brief description of study
The purpose of this study is to investigate the effect of balcinrenone/dapagliflozin compared with dapagliflozin, on the risk of CV death, HF event with and without hospitalization, in patients with chronic HF, impaired kidney function, and who have had a recent HF event.
Detailed description of study
Eligible patients will randomly be assigned with a 1:1:1 ratio to receive once daily administration of one capsule and one tablet of one of the following treatments:
- Balcinrenone/dapagliflozin 15 mg/10 mg capsule and matching placebo for dapagliflozin 10 mg tablet
- Balcinrenone/dapagliflozin 40 mg/10 mg capsule and matching placebo for dapagliflozin 10 mg tablet
- Dapagliflozin 10 mg tablet and matching placebo for balcinrenone/dapagliflozin capsule
The study is event driven, and the average study duration for a participant is estimated to be 22 months including screening period, 20 months blinded treatment period and a one-month follow-up period on open-label dapagliflozin.
The study will be conducted at approximately 700 sites in approximately 40 countries globally.
Eligibility of study
You may be eligible for this study if you meet the following criteria:
- Conditions: Heart Failure, Impaired Kidney Function
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Age: 18 years - 100 years
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Gender: All
Inclusion Criteria:
- Age ≥ 18 years
- Documented diagnosis of symptomatic HF (NYHA functional class II-IV)
- Having had a recent HF event within 6 months (hospitalization or urgent visit)
- Have a LVEF value from an assessment within the last 12 months
- Managed with SoC therapy for HF and renal impairment according to local guidelines
- NT-proBNP must be >300 pg/mL (>600 pg/mL if concomitant atrial fibrillation or atrial flutter)
- Not taking an MRA
- An eGFR ≥ 20 to < 60 mL/min/1.73 m2
- Serum/plasma potassium ≥ 3.5 mmol/L and ≤ 5.0 mmol/L
Exclusion Criteria:
- Acute coronary syndrome (unstable angina or myocardial infarction), stroke or transient ischaemic attack within the previous 3 months
- Major cardiac surgery, coronary revascularisation or valvular repair or replacement, or implantation of a Cardiac resynchronisation therapy device within 3 months prior to enrolment or planned to undergo any of these operations
- History of hypertrophic obstructive cardiomyopathy
- Complex congenital heart disease or severe uncorrected primary valvular disease
- Symptomatic bradycardia or second- or third-degree heart block without a pacemaker
- Systolic BP < 100 mmHg, or symptomatic hypotension within the past 24 hours
- Primary pulmonary hypertension, chronic pulmonary embolism, severe pulmonary disease including COPD or exacerbation of COPD requiring invasive mechanical ventilation assistance within 12 months prior to enrolment
- Type 1 diabetes mellitus
- Kidney replacement therapy in the past 4 weeks, currently requiring kidney replacement or imminent plan to start kidney replacement therapy
- Hepatic disease, including active HBV or HCV infection, or other cause of hepatitis, and/or hepatic impairment (Child-Pugh class A-C), AST or ALT >3 × ULN; or TBL > 2 × ULN at time of screening
- Suspected or confirmed COVID-19 infection within the last 4 weeks or hospitalisation for COVID-19 within the last 12 weeks
- Treatment with strong or moderate CYP3A4 inhibitor or inducer
This study investigates the effects of an investigational medication on heart failure and kidney function. Heart failure is a condition where the heart cannot pump blood as well as it should. This study compares the investigational medication to another treatment to see how they affect heart failure events and cardiovascular death in patients with heart failure and impaired kidney function.
Participants will be randomly assigned to one of three study arms. Each participant will take a capsule and a tablet each day. The study arms include different doses of the investigational medication or a placebo, which is an inactive substance that looks like the investigational medicine but does not contain any medicine. The study will collect data on heart failure events and kidney function.
- Who can participate: Adults aged 18 and older with symptomatic heart failure and impaired kidney function can participate.
- Study details: Participants will be randomly assigned to receive one of three treatments, including the investigational medication or a placebo. They will take one capsule and one tablet daily. The study will monitor heart failure events and kidney function.
- Study timelines: The study will last 22 months.
