Heart Failure and Impaired Kidney Function
Conditions
Interventions
Test group 1:Balcinrenone/Dapagliflozin 40 mg/10 mg
Control group:Dapagliflozin 10 mg
Test group 2:Balcinrenone/Dapagliflozin 15 mg/10 mg
Sponsors
Peking Union Medical College Hospital
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1. Participant must be >= 18 years old, at the time of signing the informed consent. 2. Documented diagnosis of symptomatic HF (NYHA functional Class II to IV), present before the last event. 3. Having had a recent HF event, defined as either:a. A hospitalisation primarily for a HF indication including signs and symptoms of congestions and use of parenteral medications for HF during admission within 6 months prior to randomisation, OR b. An urgent HF visit with outpatient parenteral medications for HF within 6 months prior to randomisation, OR c. Currently hospitalised due to worsening of chronic HF, but with none of the following within the last 24 hours of randomisation: i. Invasive or non-invasive ventilation ii. IV vasopressor, IV vasodilator use including nitrates or IV inotropes iii. Increase in dose of IV diuretics; 4. Have a LVEF value from an assessment within the last 12 months. Participants not assessed within that timeframe may undergo a local echocardiogram at the time of enrolment. a. Participant who have undergone coronary revascularisation (percutaneous coronary intervention or coronary artery bypass grafting), valve repair/replacement or implantation of a cardiac resynchronisation therapy device or any other surgical, device that might improve LVEF must have had a measurement of LVEF at least 3 months after the intervention in order to be eligible. 5. Managed with SoC therapy for HF and impairmed kidney function according to local guidelines (with the exception of MRA), with or without SGLT2 inhibitors. a. SGLT2 inhibitors can be taken up to the day before randomisation (ie, start of double-blind treatment). Participants on SGLT2i prior to randomisation will switch to blinded study therapy at randomisation and will discontinue the SGLT2i they were prescribed before the randomisation. 6. Not taking an MRA, for one of the following reasons: a. Mineralocorticoid receptor antagonist not indicated due to LVEF of > 40% (HFmrEF and HFpEF)b. Mineralocorticoid receptor antagonist not recommended or contraindicated due to low eGFR (as per local guidelines) c. History of MRA adverse reaction/intolerance from approved MRA; Hyperkalaemia, Worsening kidney function, Hypotension, Hormonal side effects (such as gynecomastia, erectile dysfunction) d. Specific concerns for adverse reactions from approved MRAs; hyperkalaemia, worsening kidney function, hypotension, hormonal side effects (such as gynecomastia, erectile dysfunction); 7. An eGFR >= 20 to = 3.5 mmol/L and 300 pg/mL at Visit 1 (> 600 pg/mL if concomitant atrial fibrillation or atrial flutter at Visit 1). If available, a local laboratory result (serum or plasma) from 100 pg/mL if sinus rhythm (> 300 pg/mL if concomitant atrial fibrillation at Visit 1). 10. Contraceptive use by females should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. a. Females not of childbearing potential are defined as females who are either permanently sterilised (hysterec
Exclusion criteria
Exclusion criteria: 1. Systolic BP = 160 mmHg if on treatment with = 180 mmHg irrespective of treatments, at enrolment or randomisation. 3. Acute coronary syndrome (unstable angina or myocardial infarction), stroke or transient ischaemic attack within the previous 3 months. 4. 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 after randomisation 5 History of the following cardiomyopathies: hypertrophic obstructive, infiltrative (such as but not limited to diagnosed amyloidosis), restrictive, genetic or familial, arrhythmogenic right ventricular cardiomyopathy; Chaga’s cardiomyopathy is permitted; 5. History of myocardial disease: hypertrophic obstructive, infiltrative (including but not limited to diagnosed amyloidosis), restrictive, hereditary or familial, arrhythmogenic right ventricular cardiomyopathy; Allowing patients with Chagas cardiomyopathy; 6. Active myocarditis or pericardial causes of HF (eg, constriction or tamponade); 7. Complex congenital heart disease or severe uncorrected primary valvular disease; 8. Symptomatic bradycardia or second- or third-degree heart block without a pacemaker; 9. History of mechanical circulatory support (such as left ventricular assist device), heart transplant or on heart transplant list); 10. Probable alternative or concomitant diagnoses which could account for the participant’s HF symptoms and signs (eg, severe anaemia, hypothyroidism, nephrotic syndrome); 11. Primary pulmonary hypertension, chronic pulmonary embolism, severe pulmonary disease including COPD (eg, requiring home oxygen or frequent hospitalisation) or exacerbation of COPD requiring invasive mechanical ventilation assistance within 12 months prior to enrolment); 12. Has received kidney replacement therapy in the past 4 weeks, currently requiring kidney replacement or imminent plan to start kidney replacement therapy. 13. Hepatic disease, including active HBV or HCV infection, or other cause of hepatitis, and/or hepatic impairment (Child-Pugh class B-C; or any of AST or ALT > 3 × ULN; or TBL > 2 × ULN at time of screening at Visit 1). An isolated increase in total bilirubin in patients with known Gilbert’s syndrome is not a reason for exclusion, provided that direct bilirubin is normal. 14. Type 1 diabetes mellitus. 15. Addison’s disease. 16. Any of the following related to COVID-19 infection: a. Suspected (as judged by PI) or confirmed COVID-19 infection within the last 4 weeks prior to enrolment (Visit 1) or at randomisation (Visit 2). b. Hospitalisation for COVID-19 within the last 12 weeks prior to enrolment (Visit 1). 17. Any condition outside the kidney and CV disease area, such as but not limited to active malignancy requiring treatment, with short life expectancy based on the Investigator’s clinical judgement. 18. 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. 19. Treatment with an approved MRA (eg, spironolactone, eplerenone, finerenone) for more than 7 days within the last month prior to randomisation or planned treatment with an MRA. 20. Participants treated with strong or moderate CYP3A4 inhibitor or inducer; 21. Parti
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The time until the first occurrence of any component event in the composite endpoint: CV death ? Hospitalization due to HF Untreated HF events; | — |
Secondary
| Measure | Time frame |
|---|---|
| Total incidence of composite endpoint components (first and recurrence): CV death ? Hospitalization due to HF Untreated HF events;Total incidence of HF hospitalization (first and recurrent);Until the time of CV's death;Hierarchical composite endpoint consisting of all-cause mortality, total HF events, and changes in KCCQ total symptom scores from baseline to 24 weeks after randomization;Until the time of all-cause death; | — |
Countries
China
Contacts
Public ContactZhang Shuyang
Peking Union Medical College Hospital
Outcome results
None listed