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

About the Study

Currently Recruiting: Sites

Study Drug/Intervention: Balcinrenone/Dapagliflozin

Anticipated Sample Size: 4,800 patients

Study Timeline: This study is expected to conclude in June 2027. ID: NCT06307652



The purpose of the study is to evaluate the safety and efficacy of balcinrenone in fixed combination with dapagliflozin (an SGLT2 inhibitor) compared with dapagliflozin in patients with chronic HF, across the full range of LVEF and impaired kidney function with eGFR of ≥ 20 to < 60 mL/min/1.73 m2. 

Study Objective

To determine whether balcinrenone/dapagliflozin is superior to dapagliflozin in reducing the risk of CV death and HF events with and without hospitalization.

Unique Aspects of Project

Our goal is to reach out to the community and enroll a more diverse group of people.

Inclusion & Exclusion Criteria

Inclusion Criteria

  1. Participant must be ≥ 18 years old at the time of signing the informed consent.
  2. A 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:
    1. A hospitalization primarily for an HF indication including signs and symptoms of congestions and use of parenteral medications for HF during admission within six months prior to randomization, OR
    2. An urgent HF visit with outpatient parenteral medications for HF within six months prior to randomization, OR
    3. Currently hospitalized due to worsening of chronic HF, but with none of the following within the last 24 hours of randomization:
      1. Invasive or non-invasive ventilation
      2. IV vasopressor, IV vasodilator use including nitrates or IV inotropes
      3. Increase in dose of IV diuretics
  4. Have an 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.
    1. Participants who have undergone coronary revascularization (percutaneous coronary intervention or coronary artery bypass grafting), valve repair/replacement, or implantation of a cardiac resynchronization therapy device or any other surgical device that might improve LVEF must have had a measurement of LVEF at least three months after the intervention in order to be eligible.
  5. Managed with SoC therapy for HF and impaired kidney function according to local guidelines (with the exception of MRA), with or without SGLT2 inhibitors.
    1. SGLT2 inhibitors can be taken up to the day before randomization (i.e., start of double-blind treatment). Participants on SGLT2i prior to randomization will switch to blinded study therapy at randomization and will discontinue the SGLT2i they were prescribed before the randomization.
  6. Not taking an MRA for one of the following reasons:
    1. Mineralocorticoid receptor antagonist not indicated due to LVEF of > 40% (HFmrEF and HFpEF)
    2. Mineralocorticoid receptor antagonist not recommended or contraindicated due to low eGFR (as per local guidelines)
    3. History of MRA adverse reaction/intolerance from approved MRA; Hyperkalaemia, Worsening kidney function, Hypotension, Hormonal side effects (such as gynecomastia, erectile dysfunction)
    4. Specific concerns for adverse reactions from approved MRAs; hyperkalemia, worsening kidney function, hypotension, hormonal side effects (such as gynecomastia, erectile dysfunction)
  7. An eGFR ≥ 20 to < 60 mL/min/1.73 m2, from Visit 1*.
  8. Serum or plasma potassium ≥ 3.5 mmol/L and ≤ 5.0 mmol/L at Visit 1.
  9. NT-proBNP must be > 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 < 30 days prior to Visit 1 can be used for inclusion. For participants randomized while hospitalized, any local value must have been collected during the index event.
    1. For participants randomized while hospitalized and where NT-proBNP is not available in local laboratory results used to determine eligibility, BNP result (serum or plasma) must be > 100 pg/mL if sinus rhythm (> 300 pg/mL if concomitant atrial fibrillation at Visit 1).

Exclusion Criteria

  1. Systolic BP < 100 mmHg, or symptomatic hypotension within the past 24 hours, at randomization.
  2. Systolic BP ≥ 160 mmHg if on treatment with < 3 blood pressure lowering medications or ≥ 180 mmHg irrespective of treatments, at enrolment or randomization.
  3. Acute coronary syndrome (unstable angina or myocardial infarction), stroke, or transient ischaemic attack within the previous three months.
  4. Major cardiac surgery, coronary revascularisation or valvular repair or replacement, or implantation of a Cardiac resynchronization therapy device within three months prior to enrolment or planned to undergo any of these operations after randomization
  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
  6. Active myocarditis or pericardial causes of HF (e.g., constriction or tamponade)
  7. Complex congenital heart disease or severe uncorrected primary valvular disease

Study Timeline

Duration of Study Participation

The estimated mean treatment period is approximately 20 months for a study participant, followed by a one-month follow-up period. The participants in the study may be in the study for a shorter or longer time, depending on when the participant enters the study. The study duration may change if the event rate or randomization rate is different than anticipated.

Sponsor/Funding Support

AstraZeneca AB

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