Balcinrenone + Dapagliflozin for Heart Failure

(BalanceD-HF Trial)

Recruiting at 453 trial locations

Overseen By AstraZeneca Clinical Study Information Center

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: AstraZeneca

Must not be taking: CYP3A4 inhibitors

Disqualifiers: Recent ACS, Major surgery, Type 1 diabetes, Severe pulmonary disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

Duration: 20 months

4800 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are taking a strong or moderate CYP3A4 inhibitor or inducer (types of drugs that affect how your body processes other medications).

What data supports the effectiveness of the drug Balcinrenone/Dapagliflozin for heart failure?

Research shows that dapagliflozin, a part of the treatment, significantly reduces the risk of worsening heart failure and death in patients with heart failure, regardless of whether they have diabetes. It also decreases the chances of being hospitalized again for heart failure. ^{1 2 3 4 5}

Is the combination of Balcinrenone and Dapagliflozin safe for humans?

Dapagliflozin is generally well tolerated and has a consistent safety profile in treating heart failure, as shown in several studies. However, there is no specific safety data available for the combination of Balcinrenone and Dapagliflozin. ^{6 7 8 9 10}

What makes the drug Balcinrenone/Dapagliflozin unique for treating heart failure?

Balcinrenone/Dapagliflozin is unique because it combines dapagliflozin, a sodium-glucose cotransporter-2 (SGLT2) inhibitor, which has been shown to improve heart failure outcomes, with another component, potentially offering a novel approach to managing heart failure, especially in patients with type 2 diabetes. ^{1 11 12 13 14}

Eligibility Criteria

This trial is for patients with chronic heart failure and poor kidney function who recently had a heart-related event. Participants should be on standard-of-care treatments for their condition. Specific eligibility details are not provided, but typically, trials exclude individuals with conditions or circumstances that could interfere with the study's outcomes.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2 months

Treatment

Participants receive once daily administration of balcinrenone/dapagliflozin or dapagliflozin for 20 months

20 months

Follow-up

Participants are monitored for safety and effectiveness after treatment with open-label dapagliflozin

1 month

Treatment Details

Interventions

• Balcinrenone/Dapagliflozin

Trial Overview The study tests the effects of combining balcinrenone/dapagliflozin at two different doses versus dapagliflozin alone in managing heart failure. It's a Phase III trial where participants are randomly assigned to one of the treatment groups and neither they nor the researchers know who gets which treatment (double-blind).

Participant Groups

Group I: balcinrenone/dapagliflozin 40 mg/10 mg Experimental Treatment 1 Intervention

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

Group II: balcinrenone/dapagliflozin 15 mg/10 mg Experimental Treatment 1 Intervention

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

Group III: dapagliflozin 10 mg Active Control 1 Intervention

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

Who Is Running the Clinical Trial?

AstraZeneca

Lead Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Findings from Research

Dapagliflozin, an SGLT2 inhibitor approved for heart failure treatment, significantly reduces the risk of worsening heart failure or cardiovascular death compared to placebo, regardless of whether patients have Type 2 diabetes.

The paper reviews the drug's chemistry, pharmacodynamics, and pharmacokinetics, highlighting its clinical efficacy in patients with heart failure and reduced ejection fraction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of dapagliflozin in the treatment of heart failure. Sotirakos, S.[2021]

In the DAPA-HF trial involving 4744 patients, the SGLT2 inhibitor dapagliflozin significantly reduced the risk of worsening heart failure and death, with a hazard ratio of 0.74, indicating a strong protective effect.

The benefits of dapagliflozin were consistent across various background heart failure therapies, showing no significant differences in effectiveness based on whether patients were taking diuretics, beta-blockers, or other heart medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of dapagliflozin in DAPA-HF according to background heart failure therapy. Docherty, KF., Jhund, PS., Inzucchi, SE., et al.[2022]

In the DAPA-HF trial, dapagliflozin significantly reduced the risk of worsening heart failure episodes and cardiovascular death, with a 36% lower incidence in patients taking dapagliflozin compared to placebo over a median follow-up of 18.2 months.

Outpatient worsening of heart failure was common and associated with a higher risk of death, but dapagliflozin effectively lowered these events, demonstrating its efficacy in managing heart failure alongside standard therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Dapagliflozin on Outpatient Worsening of Patients With Heart Failure and Reduced Ejection Fraction: A Prespecified Analysis of DAPA-HF. Docherty, KF., Jhund, PS., Anand, I., et al.[2021]

In a study of 1595 hospitalized heart failure patients in Spain, 75.2% were eligible for dapagliflozin, which is projected to significantly reduce rehospitalization and mortality rates.

Full implementation of dapagliflozin could lead to a 3.5% reduction in mortality and a 6.5% reduction in heart failure readmissions, indicating its potential effectiveness in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Projected effectiveness of dapagliflozin in heart failure with reduced ejection fraction in clinical practice. Montero-Pérez-Barquero, M., Escobar-Cervantes, C., Arévalo-Lorido, JC., et al.[2023]

A randomized controlled trial (RCT) showed that dapagliflozin significantly improves cardiovascular outcomes in heart failure patients, regardless of whether they have diabetes.

This suggests that dapagliflozin may be an effective treatment option for enhancing heart health in a broad range of heart failure patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prescribe an SGLT2 inhibitor for heart failure in the absence of diabetes? Koenigsberger, D., Marquez, A., Hughes, PR.[2022]

Dapagliflozin, an SGLT2 inhibitor, has been shown to significantly reduce the risk of cardiovascular death or hospitalization for heart failure in patients with heart failure with reduced ejection fraction (HFrEF), regardless of whether they have type 2 diabetes.

In the DAPA-HF trial, dapagliflozin was well tolerated and demonstrated a lower risk of worsening heart failure or cardiovascular death compared to placebo, making it a valuable treatment option for adults with symptomatic HFrEF.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dapagliflozin: A Review in Symptomatic Heart Failure with Reduced Ejection Fraction. Blair, HA.[2022]

In the DAPA-HF trial involving 4742 patients with heart failure and reduced ejection fraction (HFrEF), dapagliflozin significantly reduced the risk of cardiovascular death or worsening heart failure, regardless of baseline kidney function, indicating its efficacy across different eGFR levels.

Dapagliflozin also slowed the decline in kidney function over time, with a significantly less rate of eGFR decline compared to placebo, demonstrating its potential renal protective effects even in patients without diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of Dapagliflozin on Renal Function and Outcomes in Patients With Heart Failure With Reduced Ejection Fraction: Results of DAPA-HF. Jhund, PS., Solomon, SD., Docherty, KF., et al.[2021]

Dapagliflozin, a sodium-glucose cotransporter 2 (SGLT-2) inhibitor, has been approved for treating symptomatic heart failure and has shown to significantly reduce the risk of cardiovascular mortality and hospitalization for heart failure in patients, regardless of their diabetes status.

The drug has a comparable safety profile to other treatments and is generally well tolerated, making it a promising option for managing heart failure alongside existing therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current Status of Dapagliflozin in Congestive Heart Failure. Palandurkar, G., Kumar, S.[2022]

This meta-analysis aims to evaluate the efficacy and safety of dapagliflozin in treating chronic heart failure (CHF) by reviewing randomized controlled trials from multiple databases, which will help inform clinical decision-making.

Dapagliflozin is a new drug for chronic cardiovascular disease, and this study seeks to provide robust evidence regarding its effectiveness and safety profile for patients with CHF.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of dapagliflozin in the treatment of chronic heart failure: A protocol for systematic review and meta-analysis. Dong, X., Ren, L., Liu, Y., et al.[2023]

A long-term analysis of over 1,000 patients with congestive heart failure (CHF) showed that lisinopril is generally well tolerated, with a 44.1% adverse event rate compared to 39.4% for placebo, indicating its safety in this population.

Among the 620 patients studied for nearly 4 years, 33.1% discontinued treatment, primarily due to clinical adverse events or death, but the overall safety profile of lisinopril was comparable to other angiotensin-converting enzyme inhibitors, suggesting it is a viable option for CHF management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of long-term use of lisinopril for congestive heart failure. Moyses, C., Higgins, TJ.[2019]

Newer diabetes medications, such as DPP-4 inhibitors, GLP-1 agonists, and SGLT-2 inhibitors, are being studied for their potential benefits in patients with heart failure, a condition that affects 25-35% of those with type 2 diabetes.

These drug classes are not only being evaluated for cardiovascular safety but also for their impact on heart function, quality of life, and progression of heart disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treating Diabetes in Patients with Heart Failure: Moving from Risk to Benefit. DeFilippis, EM., Givertz, MM.[2019]

In a study involving 125 patients with type-2 diabetes and heart failure, licogliflozin (10 mg) significantly reduced NT-proBNP levels after 12 weeks, indicating potential heart health benefits.

Licogliflozin also showed improvements in blood sugar control and weight loss similar to empagliflozin, with mild adverse events reported, suggesting it is a safe and effective option for managing diabetes in heart failure patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of the dual sodium-glucose linked transporter inhibitor, licogliflozin vs placebo or empagliflozin in patients with type 2 diabetes and heart failure. de Boer, RA., Núñez, J., Kozlovski, P., et al.[2022]

Dapagliflozin, an SGLT2 inhibitor, significantly slows the migration of myocardial fibroblasts from patients with heart failure and reduces the expression of inflammatory and fibrosis-related markers, indicating its potential to improve heart function in HFrEF patients.

The combination of dapagliflozin with LCZ696 enhances the anti-migratory effects on fibroblasts, while spironolactone alters the signaling pathways activated by dapagliflozin, suggesting that these drugs can work together to modulate heart failure mechanisms differently.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Direct actions of dapagliflozin and interactions with LCZ696 and spironolactone on cardiac fibroblasts of patients with heart failure and reduced ejection fraction. Ortega-Paz, L., Cristóbal, H., Ortiz-Perez, JT., et al.[2023]

Dapagliflozin is more cost-effective than sacubitril-valsartan (ARNI) for preventing heart failure events in patients with heart failure and type 2 diabetes, with a cost needed to treat (CNT) of $108,563 compared to $290,671 for the ARNI.

The annualized number needed to treat (NNT) was significantly lower for dapagliflozin (24) compared to the ARNI (57), indicating that dapagliflozin is more efficient in reducing hospitalizations and cardiovascular mortality in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dapagliflozin Versus Sacubitril-Valsartan to Improve Outcomes of Patients with Reduced Ejection Fraction and Diabetes Mellitus. Hammerman, A., Azuri, J., Aboalhasan, E., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Evaluation of dapagliflozin in the treatment of heart failure. [2021]

2. England pubmed.ncbi.nlm.nih.gov

Effects of dapagliflozin in DAPA-HF according to background heart failure therapy. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Effect of Dapagliflozin on Outpatient Worsening of Patients With Heart Failure and Reduced Ejection Fraction: A Prespecified Analysis of DAPA-HF. [2021]

4. England pubmed.ncbi.nlm.nih.gov

Projected effectiveness of dapagliflozin in heart failure with reduced ejection fraction in clinical practice. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Prescribe an SGLT2 inhibitor for heart failure in the absence of diabetes? [2022]

6. New Zealand pubmed.ncbi.nlm.nih.gov

Dapagliflozin: A Review in Symptomatic Heart Failure with Reduced Ejection Fraction. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Efficacy of Dapagliflozin on Renal Function and Outcomes in Patients With Heart Failure With Reduced Ejection Fraction: Results of DAPA-HF. [2021]

8. United States pubmed.ncbi.nlm.nih.gov

Current Status of Dapagliflozin in Congestive Heart Failure. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

Efficacy and safety of dapagliflozin in the treatment of chronic heart failure: A protocol for systematic review and meta-analysis. [2023]

10. United States pubmed.ncbi.nlm.nih.gov

Safety of long-term use of lisinopril for congestive heart failure. [2019]

11. United States pubmed.ncbi.nlm.nih.gov

Treating Diabetes in Patients with Heart Failure: Moving from Risk to Benefit. [2019]

12. England pubmed.ncbi.nlm.nih.gov

Effects of the dual sodium-glucose linked transporter inhibitor, licogliflozin vs placebo or empagliflozin in patients with type 2 diabetes and heart failure. [2022]

13. England pubmed.ncbi.nlm.nih.gov

Direct actions of dapagliflozin and interactions with LCZ696 and spironolactone on cardiac fibroblasts of patients with heart failure and reduced ejection fraction. [2023]

14. New Zealand pubmed.ncbi.nlm.nih.gov

Dapagliflozin Versus Sacubitril-Valsartan to Improve Outcomes of Patients with Reduced Ejection Fraction and Diabetes Mellitus. [2022]