Baxdrostat + Dapagliflozin for Heart Failure

(Prevent-HF Trial)

Recruiting at 607 trial locations

Overseen By AstraZeneca Clinical Study Information Center

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: AstraZeneca

Must be taking: SGLT2 inhibitors

Must not be taking: Mineralocorticoid antagonists, Potassium-sparing diuretics

Disqualifiers: Heart failure, Severe hepatic impairment, 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

Compensation: Varies

Number of Visits: 3

Duration: Up to 38 months

11300 Participants Needed

Trial Summary

What is the purpose of this trial?

Participants include men and women ≥ 40 years of age with T2DM, established CV disease, a history of HTN with an SBP of at least 130 mmHg at screening, who meet the predefined serum potassium level, and with at least one additional risk factor for HF. The study will include an optional pre-screening period to facilitate sites' identification of potentially eligible participants to enter the full screening assessments. Participants will not be required to visit the site and no informed consent is required for the optional pre-screening period. The pre-screening assessments do not replace the full screening tests at Visit 1. Upon entering the screening period, all consented participants (after signature of screening ICF) will be screened during an up to 14-day screening period. Participants who meet all screening inclusion/exclusion criteria but are not treated with SGLT2i or are treated for less than 4 weeks will enter a run-in period with dapagliflozin 10 mg once daily for at least 4 weeks (and not more than 6 weeks) before randomisation. Site visits will take place at approximately 2-, 4-, 8-, 16-, and 34-weeks following randomisation. Thereafter visits will occur approximately every 4 months. The study closure procedures will be initiated when the predetermined number of the first secondary endpoint events (ie, the composite of hospitalisation for HF or CV death) is predicted to have occurred i.e., the PACD. In case of premature discontinuation of the blinded study intervention, participants will remain in the study. Unless a participant meets the dapagliflozin specific discontinuation criteria, they will continue to receive open label dapagliflozin 10 mg. It is important that the scheduled study visits and data collection continue according to the study protocol.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, such as mineralocorticoid receptor antagonists, potassium-sparing diuretics, and potassium binders, at least 4 weeks before screening. If you are on these medications, you will need to discontinue them to participate in the study.

What data supports the effectiveness of the drug Baxdrostat + Dapagliflozin for heart failure?

Research shows that dapagliflozin, a component of the treatment, is effective in reducing the risk of heart failure worsening and cardiovascular death in patients with heart failure with reduced ejection fraction, as demonstrated in the DAPA-HF trial. Additionally, dapagliflozin has been shown to improve symptoms like shortness of breath in patients with heart failure, without negatively affecting kidney function. ^{1 2 3 4 5}

Is the combination of Baxdrostat and Dapagliflozin safe for humans?

Dapagliflozin, also known as Farxiga or Forxiga, is generally well tolerated and has a consistent safety profile when used for heart failure and type 2 diabetes. It has been approved for reducing risks related to heart and kidney conditions, and its safety has been confirmed in various studies. ^{1 2 3 4 6}

What makes the drug combination of Baxdrostat and Dapagliflozin unique for heart failure?

The combination of Baxdrostat and Dapagliflozin is unique because Dapagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, is already known to reduce the risk of cardiovascular death and hospitalization for heart failure, and when combined with Baxdrostat, it may offer additional benefits for heart failure management. ^{1 2 3 4 7}

Eligibility Criteria

This trial is for men and women over 40 with type 2 diabetes, cardiovascular disease, high blood pressure (SBP ≥130 mmHg), a specific potassium level in their blood, and at least one other risk factor for heart failure. They must not have been treated with SGLT2 inhibitors or only have had such treatment for less than four weeks.

Inclusion Criteria

Central laboratory serum potassium ≥ 3.0 to ≤ 4.8 mmol/L at screening

I am 40 years old or older.

I have type 2 diabetes and need treatment.

Exclusion Criteria

I have not had a heart attack in the last 3 months.

I have not had dialysis in the last 3 months.

I have severe liver problems (Child-Pugh Class C).

Timeline

Pre-screening

Optional pre-screening period to identify potentially eligible participants

Not specified

No visits required

Screening

Participants are screened for eligibility to participate in the trial

2 weeks

1 visit (in-person)

Run-in

Participants receive dapagliflozin 10 mg once daily for at least 4 weeks before randomisation

4-6 weeks

Treatment

Participants receive either baxdrostat/dapagliflozin or placebo/dapagliflozin with site visits at specified intervals

Up to 38 months

Visits at 2, 4, 8, 16, 34 weeks, then every 4 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Baxdrostat
• Dapagliflozin

Trial Overview The study tests Baxdrostat combined with Dapagliflozin against a placebo paired with Dapagliflozin to see which is better at preventing heart failure and cardiovascular death. Participants will be randomly assigned to either group and followed up regularly after taking the medication.

Participant Groups

Group I: Placebo/Dapagliflozin Experimental Treatment 1 Intervention

Patients will receive a dose of dapagliflozin in combination with matching placebo

Group II: Baxdrostat/Dapagliflozin Experimental Treatment 1 Intervention

Participants randomised to the baxdrostat/dapagliflozin arm will initially receive a dose of baxdrostat lower dose and dapagliflozin. For participants that meet the up-titration criteria, baxdrostat may be up-titrated to higher dose.

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, 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]

Dapagliflozin (Farxiga) is approved for reducing the risk of declining kidney function and kidney failure in adults with chronic kidney disease, regardless of whether they have type 2 diabetes.

It also helps lower the risk of cardiovascular death and hospitalization for heart failure, highlighting its efficacy in managing both kidney and heart health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antidiabetic Drug Approved to Reduce Risk of Kidney Disease. Aschenbrenner, DS.[2023]

The fixed-dose combination of dapagliflozin and saxagliptin (QTERN) effectively reduces hemoglobin A1C levels in patients with uncontrolled type 2 diabetes when used alongside metformin, showing a significant difference in A1C reduction compared to other combinations.

QTERN is generally well tolerated, but its use may be limited by cost and modest efficacy in A1C reduction, highlighting the need for further research on its long-term effects on diabetes complications and cardiovascular health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dapagliflozin/Saxagliptin Fixed-Dose Tablets: A New Sodium-Glucose Cotransporter 2 and Dipeptidyl Peptidase 4 Combination for the Treatment of Type 2 Diabetes. Coppenrath, VA., Hydery, T.[2022]

Dapagliflozin (DAPA) is an effective SGLT2 inhibitor for treating type 2 diabetes, showing favorable pharmacokinetics and pharmacodynamics that help lower blood sugar levels while having beneficial effects on other metabolic risk factors.

While DAPA is generally safe, it carries an increased risk of genital and urinary infections, and concerns about bladder cancer and cardiovascular safety remain, prompting the FDA to seek further data on these issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics, pharmacodynamics and clinical efficacy of dapagliflozin for the treatment of type 2 diabetes. Maranghi, M., Carnovale, A., Durante, C., et al.[2021]

Dapagliflozin is an effective treatment for type 2 diabetes, proven through multiple controlled clinical trials that assess its efficacy, safety, and tolerability.

It is approved by the FDA for use as a standalone therapy or in combination with other glucose-lowering medications, including insulin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dapagliflozin: A Sodium Glucose Cotransporter 2 Inhibitor for the Treatment of Diabetes Mellitus. Davis, PN., Ndefo, UA., Oliver, A.[2021]

Sotagliflozin, the first dual inhibitor of SGLT1 and SGLT2, has shown significant efficacy in reducing cardiovascular and heart failure events in patients with type 2 diabetes, as demonstrated in the SOLOIST-WHF trial with a hazard ratio of 0.67.

While sotagliflozin expands treatment options for heart failure, existing SGLT2 inhibitors like dapagliflozin and empagliflozin have more robust evidence supporting their use, particularly in heart failure and chronic kidney disease, indicating that further research is needed to clarify sotagliflozin's role in treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sotagliflozin: Efficacy, Safety, and Potential Therapeutic Applications in Heart Failure. Long, A., Salvo, M.[2023]

References

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

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

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

Antidiabetic Drug Approved to Reduce Risk of Kidney Disease. [2023]

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

Dapagliflozin/Saxagliptin Fixed-Dose Tablets: A New Sodium-Glucose Cotransporter 2 and Dipeptidyl Peptidase 4 Combination for the Treatment of Type 2 Diabetes. [2022]

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

Pharmacokinetics, pharmacodynamics and clinical efficacy of dapagliflozin for the treatment of type 2 diabetes. [2021]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Adding Dapagliflozin to Furosemide in Type 2 Diabetic Patients With Decompensated Heart Failure and Reduced Ejection Fraction. [2021]

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

Dapagliflozin: A Sodium Glucose Cotransporter 2 Inhibitor for the Treatment of Diabetes Mellitus. [2021]

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

Sotagliflozin: Efficacy, Safety, and Potential Therapeutic Applications in Heart Failure. [2023]