A Phase III, Randomised, Placebo-controlled, Event-driven Study to Evaluate the Effect of Baxdrostat in Combination With Dapagliflozin Compared With Dapagliflozin Alone on the Risk of Incident Heart Failure and Cardiovascular Death

Plain English Summary

Phase III Study Investigating Heart Failure and Cardiovascular Death With Baxdrostat in Combination With Dapagliflozin is a Phase 3 clinical trial sponsored by AstraZeneca studying Heart Failure. Tests if Baxdrostat combined with Dapagliflozin can reduce the risk of heart failure and cardiovascular death compared to Dapagliflozin alone. For adults over 40 with type 2 diabetes, established cardiovascular disease, and a history of high blood pressure, who also have at least one additional risk factor for heart failure. Participation involves up to 38 months of treatment with regular site visits every 2, 4, 8, 16, and 34 weeks, and optional pre-screening. Alternative treatments include other medications for heart failure and cardiovascular disease. The trial aims to enroll 11300 participants.

Official Summary

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.

Who Can Participate

Here is what you need to know about eligibility for this trial. Eligible participants must be at least 40 years old, have type 2 diabetes, established cardiovascular disease, and a history of high blood pressure. Participants must also have at least one additional risk factor for heart failure, such as age over 70 or elevated NT-proBNP levels. Excluded are those with a confirmed history of heart failure, severe kidney impairment, or certain medications that could interfere with the study. This trial is studying Heart Failure, so participants generally need a confirmed diagnosis. The trial is currently accepting new participants.

What They're Measuring

The primary outcome measures the risk of heart failure and cardiovascular death, which directly impacts patient survival and quality of life. The specific primary outcome measures are: To determine if baxdrostat/dapagliflozin is superior to placebo/dapagliflozin in reducing the risk of an HF event or CV death (Event driven; Up to 38 months). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 3, the final and most rigorous stage before seeking FDA approval. Phase 3 trials involve 300-3,000+ patients across multiple sites and compare the new treatment directly against the current standard of care. These pivotal trials generate the evidence needed for regulatory review. About 58% of Phase 3 drugs receive FDA approval. Successful Phase 3 results typically lead to a New Drug Application submission.

Why This Trial Matters

This trial addresses a critical gap in treatment for heart failure and cardiovascular death, potentially offering a new approach for patients at high risk. As a Phase 3 trial, positive results could directly lead to FDA approval, making this treatment available to the broader patient population. This research targets Heart Failure, where improved treatment options are needed.

Investor Insight

The large market size and competitive landscape suggest a high probability of approval, making this a promising investment opportunity. Phase 3 trials have approximately a 50-60% chance of gaining FDA approval if they reach this stage. The large enrollment target of 11300 participants suggests significant investment in this program.

Is This Trial Right for Me?

Ask your doctor if you have type 2 diabetes, established cardiovascular disease, and a history of high blood pressure. Participation involves regular site visits and taking either Baxdrostat and Dapagliflozin or a placebo and Dapagliflozin. This trial is currently recruiting participants. The trial is being conducted at 20 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: RANDOMIZED
• Model: PARALLEL
• Masking: QUADRUPLE
• Enrollment: 11,300 participants

Interventions

• DRUG: Baxdrostat and dapagliflozin — baxdrostat tablet and dapagliflozin tablet
• OTHER: Placebo and dapagliflozin — placebo tablet and dapagliflozin tablet

Primary Outcomes

• To determine if baxdrostat/dapagliflozin is superior to placebo/dapagliflozin in reducing the risk of an HF event or CV death (Event driven; Up to 38 months)

Secondary Outcomes

• To determine whether baxdrostat/dapagliflozin is superior to placebo/dapagliflozin in reducing the risk of hospitalisation for HF or CV death (Event driven; Up to 38 months)
• To determine whether baxdrostat/dapagliflozin is superior to placebo/dapagliflozin in reducing the risk of HF events (Event driven; Up to 38 months)
• To determine whether baxdrostat/dapagliflozin is superior to placebo/dapagliflozin in reducing the risk of CV death (Event driven; Up to 38 months)
• To determine whether baxdrostat/dapagliflozin is superior to placebo/dapagliflozin in reducing the risk of all-cause mortality (Event driven; Up to 38 months)
• To determine whether baxdrostat/dapagliflozin is superior to placebo/dapagliflozin in reducing the risk of 4-point MACE (CV death, MI, stroke, and hospitalisation for HF) (Event driven; Up to 38 months)

Full Eligibility Criteria

Inclusion Criteria:

* Participants of any sex and gender must be ≥ 40 years old at the time of signing the informed consent.
* Diagnosed with T2DM and requiring treatment
* Established CV disease (ischaemic heart disease, cerebrovascular disease, peripheral arterial disease)
* History of HTN and an SBP ≥ 130 mmHg at screening and ≥ 120 mmHg at the Randomisation Visit.
* At least one additional risk factor for HF:

  * Age ≥ 70 years
  * UACR \> 20 mg/g
  * eGFR \< 60 mL/min/1.73 m2
  * History of polyvascular disease (at least two of: ischaemic heart disease, cerebrovascular disease, and peripheral arterial disease)
  * History of atrial fibrillation or atrial flutter
  * NT-proBNP \> 125 ng/L

Exclusion Criteria:

* Previously confirmed diagnosis and treatment of heart failure
* An eGFR \< 30 mL/min/1.73 m2 at screening
* Known hyperkalaemia, defined as potassium ≥ 5.5 mmol/L within 3 months prior to screening
* Type 1 diabetes mellitus or uncontrolled T2DM with HbA1c \> 10.5% (\> 91 mmol/mol) at screening
* Serum sodium \< 135 mmol/L at screening, determined as per central laboratory assessment
* Stroke, transient ischaemic cerebral attack, valve implantation or valve replacement, carotid surgery, carotid angioplasty, or cardiac surgery, within 3 months prior to randomisation
* Myocardial infarction within 3 months prior to randomisation, or within 1 month prior to randomisation when there is no further planned revascularisation
* Percutaneous coronary intervention within 1 month prior to randomisation
* Known severe hepatic impairment, defined as Child-Pugh Class C, based on records that confirm documented medical history
* Documented history of adrenal insufficiency
* Any dialysis (including for acute kidney injury) within 3 months prior to screening
* Any acute kidney injury within 3 months prior to screening
* Prohibited concomitant medications

Trial Locations

• Research Site, Birmingham, Alabama, United States
• Research Site, Centreville, Alabama, United States
• Research Site, Fairhope, Alabama, United States
• Research Site, Huntsville, Alabama, United States
• Research Site, Mobile, Alabama, United States
• Research Site, Vestavia Hills, Alabama, United States
• Research Site, Gilbert, Arizona, United States
• Research Site, Glendale, Arizona, United States
• Research Site, Tempe, Arizona, United States
• Research Site, Tucson, Arizona, United States
• ...and 10 more locations

Frequently Asked Questions

Related Conditions

• Heart Failure
• Cardiovascular Disease
• Diabetes
• Kidney Disease
• High Blood Pressure
• Atrial Fibrillation
• Stroke
• Peripheral Artery Disease
• Cerebrovascular Disease
• Ischemic Heart Disease

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