Phase III/ Balcinrenone/Dapagliflozin Compared to Dapagliflozin/ Risk of Heart Failure and Death
Study Description
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 hospitalisation, in patients with chronic HF, impaired kidney function, and who have had a recent HF event.
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
- Age greater than or equal to 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 greater than 300 pg/mL (greater than 600 pg/mL if concomitant atrial fibrillation or atrial flutter)
- Not taking an MRA
- An eGFR greater than or equal to 20 to less than 60 mL/min/1.73 m2
- Serum/plasma potassium greater than or equal to 3.5 mmol/L and less than or equal to 5.0 mmol/L
- 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 less than 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 greater than 3 × ULN; or TBL greater than 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
