Baxdrostat + Dapagliflozin for Heart Failure

(Prevent-HF Trial)

Recruiting at 800 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether combining two medications, Baxdrostat and Dapagliflozin, can aid individuals with heart failure. It targets those with type 2 diabetes, heart disease, and high blood pressure, along with at least one other heart failure risk factor. Participants should not have existing heart failure but should have experienced heart issues or high blood pressure for some time. The trial aims to determine if this combination can reduce hospital visits due to heart problems or prevent heart-related deaths. As a Phase 3 trial, it represents the final step before FDA approval, offering participants an opportunity to contribute to potentially groundbreaking treatment advancements.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the combination of Baxdrostat and Dapagliflozin has been studied for safety and effectiveness. Previous patients demonstrated that this combination can significantly lower systolic blood pressure, suggesting potential benefits for those with high blood pressure.

Regarding safety, studies have examined patient tolerance to this treatment. Research data indicate it is generally well-tolerated, with most individuals not experiencing severe side effects. However, some may encounter mild to moderate side effects.

Dapagliflozin, a component of this combination, already has FDA approval for other uses, such as treating diabetes. Its established safety record in these areas adds confidence about its use in new combinations.

Overall, while the treatment appears promising, discussing any concerns with a healthcare provider before joining a clinical trial is important. They can provide advice based on personal health needs and conditions. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Baxdrostat combined with Dapagliflozin for heart failure because this combination targets the condition in a novel way. While most current treatments focus on managing symptoms or improving heart function, Baxdrostat works by inhibiting aldosterone synthase, an enzyme involved in producing aldosterone, which is linked to heart failure progression. This unique mechanism may offer more direct control over the disease's underlying causes. Additionally, combining Baxdrostat with Dapagliflozin, a well-established SGLT2 inhibitor known for its cardiovascular benefits, could enhance overall treatment effectiveness, potentially leading to improved outcomes for patients.

What evidence suggests that this trial's treatments could be effective for heart failure?

In this trial, participants will be assigned to one of two treatment arms. One arm will receive a combination of Baxdrostat and Dapagliflozin, while the other will receive Dapagliflozin with a placebo. Research has shown that combining Baxdrostat with Dapagliflozin can significantly lower the systolic blood pressure in individuals with hard-to-control hypertension. Specifically, one study found that Baxdrostat reduced this number by an average of 15.7 points, a significant decrease. Additionally, 71% of patients taking Baxdrostat achieved a blood pressure goal of less than 130. Dapagliflozin alone is already known to help manage heart failure and reduce the risk of hospital visits. Together, these treatments may improve heart health and help control blood pressure in people with type 2 diabetes. ^{2 3 5 6 7}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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 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]

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]

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]

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]

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]

Citations

1.

astrazeneca-us.com

astrazeneca-us.com/media/press-releases/2025/Baxdrostat-demonstrated-statistically-significant-and-clinically-meaningful-reduction-in-systolic-blood-pressure-in-patients-with-hard-to-control-hypertension-in-the-BaxHTN-Phase-III-trial.html

Baxdrostat demonstrated statistically significant and ...

Baxdrostat 2mg lowered systolic blood pressure by 15.7 mmHg (9.8 mmHg placebo-adjusted) from baseline, and was generally well tolerated with ...

2.

astrazenecaclinicaltrials.com

astrazenecaclinicaltrials.com/study/D6972C00003

A Phase III Study to Investigate the Efficacy and Safety of ...

The purpose of this study is to measure the efficacy and safety of baxdrostat/dapagliflozin in participants ≥ 18 years of age with CKD and HTN.

3.

clinicaltrials.gov

clinicaltrials.gov/study/NCT06268873

NCT06268873 | A Phase III Study to Investigate the ...

The purpose of this study is to measure the efficacy and safety of baxdrostat/dapagliflozin in participants ≥ 18 years of age with CKD and HTN.

4.

astrazeneca.com

astrazeneca.com/content/astraz/media-centre/press-releases/2025/bax24-phase-iii-trial-full-results.html

Baxdrostat demonstrated a statistically significant and ...

Significantly more patients treated with baxdrostat (71%) achieved ambulatory 24-hour average SBP of less than 130 mmHg compared with patients ...

5.

connect.careboxhealth.com

connect.careboxhealth.com/en-US/trial/listing/555475

The PREVENT HF study tests Baxdrostat in combination with ...

The purpose of the BaxDuo Prevent-HF clinical trial is to evaluate the safety and efficacy of the investigational therapy baxdrostat when added to Farxiga ...

6.

clinicaltrials.gov

clinicaltrials.gov/study/NCT06677060

NCT06677060 | Phase III Study Investigating Heart Failure ...

A Phase III, Randomised, Placebo-controlled, Event-driven Study to Evaluate the Effect of Baxdrostat in Combination With Dapagliflozin Compared With ...

7.

astrazenecaclinicaltrials.com

astrazenecaclinicaltrials.com/study/D6972C00002

BaxDuo-Pacific

The purpose of this study is to investigate the efficacy, safety, and tolerability of baxdrostat in combination with dapagliflozin, compared with placebo and ...