Study to Evaluate the Effect of Balcinrenone/Dapagliflozin in Patients With Heart Failure and Impaired Kidney Function
- Conditions
- Heart Failure and Impaired Kidney Function
- Interventions
- Registration Number
- NCT06307652
- Lead Sponsor
- AstraZeneca
- Brief Summary
This is a Phase III, international, multi-centre, randomised, double-blind, parallel-group, double-dummy, active-controlled, event-driven study in patients with chronic HF and impaired kidney function who had a recent HF event. The aim is to evaluate the effect of balcinrenone/dapagliflozin vs dapagliflozin, given once daily on top of other classes of SoC, on CV death and HF events.
- Detailed 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:
1. Balcinrenone/dapagliflozin 15 mg/10 mg capsule and matching placebo for dapagliflozin 10 mg tablet
2. Balcinrenone/dapagliflozin 40 mg/10 mg capsule and matching placebo for dapagliflozin 10 mg tablet
3. 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 4800
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description balcinrenone/dapagliflozin 40 mg/10 mg balcinrenone/dapagliflozin 40 mg/10 mg and matching placebo for dapagliflozin 10 mg Patients will be randomized 1:1:1 to either combination of balcinrenone/dapagliflozin and matching placebo for dapagliflozin or dapagliflozin and matching placebo for balcinrenone/dapagliflozin balcinrenone/dapagliflozin 15 mg/10 mg balcinrenone/dapagliflozin 15 mg/10 mg and matching placebo for dapagliflozin 10 mg Patients will be randomized 1:1:1 to either combination of balcinrenone/dapagliflozin and matching placebo for dapagliflozin or dapagliflozin and matching placebo for balcinrenone/dapagliflozin dapagliflozin 10 mg dapagliflozin 10 mg and matching placebo for balcinrenone/dapagliflozin Patients will be randomized 1:1:1 to either combination of balcinrenone/dapagliflozin and matching placebo for dapagliflozin or dapagliflozin and matching placebo for balcinrenone/dapagliflozin
- Primary Outcome Measures
Name Time Method Time to first occurrence of any of the components of the composite of: •CV death •HF hospitalisation •HF event without hospitalisation Approximately 38 months To determine whether balcinrenone/dapagliflozin is superior to dapagliflozin in reducing the risk of CV death and HF events with and without hospitalisation
- Secondary Outcome Measures
Name Time Method The hierarchical composite endpoint of death from any cause, total HF events, and change from baseline in KCCQ total symptom score to 24-week post-randomisation Approximately 24 weeks To determine whether balcinrenone/dapagliflozin is superior to dapagliflozin in reducing the risk of death from any cause, HF events, and improving patient reported symptoms of HF
Total occurrences (first and recurrent) of HF hospitalisations Approximately 38 months To determine whether balcinrenone/dapagliflozin is superior to dapagliflozin in reducing the rate of total HF hospitalisations
Time to death from any cause Approximately 38 months To determine whether balcinrenone/dapagliflozin is superior to dapagliflozin in reducing the risk of death from any cause
Time to CV death Approximately 38 months To determine whether balcinrenone/dapagliflozin is superior to dapagliflozin in reducing the risk of CV death
Total occurrences (first and recurrent) of the components of the composite of: •CV death •HF hospitalisation •HF event without hospitalisation Approximately 38 months To determine whether balcinrenone/dapagliflozin is superior to dapagliflozin in reducing the rate of total occurrences of CV death, and HF events with and without hospitalisation
Trial Locations
- Locations (1)
Research Site
🇻🇳Hue, Vietnam