Baxdrostat + Dapagliflozin for Heart Failure (Prevent-HF Trial)

Palo Alto (17 mi)

Age: 18+

Sex: Any

Travel: May be covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Waitlist Available

Sponsor: AstraZeneca

No Placebo Group

Pivotal Trial (Near Approval)

Prior Safety Data

Breakthrough Therapy

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.

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

I am 40 years old or older.

I have type 2 diabetes and need treatment.

I have a history of heart or blood vessel disease.

Exclusion Criteria

I am not taking medication that strongly activates liver enzymes.

I have been diagnosed with heart failure.

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

I have not had dialysis in the last 3 months.

I have had or am planning to have an organ or bone marrow transplant.

My kidney function is low, with an eGFR below 30.

I had a procedure to open blocked arteries in my heart within the last month.

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

I have been diagnosed with adrenal insufficiency.

I have type 1 diabetes or my type 2 diabetes is not under control with an HbA1c over 10.5%.

I have not had a stroke, heart surgery, or related procedures in the last 3 months.

I am currently taking medications that help my body retain potassium or control my blood pressure.

Treatment Details

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.

2Treatment groups

Experimental Treatment

Group I: Placebo/DapagliflozinExperimental Treatment1 Intervention

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

Group II: Baxdrostat/DapagliflozinExperimental Treatment1 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.