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. This study consists of a screening, a 4-week dapagliflozin run-in period for participants untreated with SGLT2i at baseline; a 24-month double-blind period in which participants will receive either baxdrostat/dapagliflozin or placebo/dapagliflozin; and approximately 12-week open-label period in which all participants will discontinue baxdrostat/placebo and receive dapagliflozin alone. Site visits will take place at 2-, 4-, 8-, and 16- weeks following randomisation. Thereafter visits will occur approximately every 4 months, until the 24-month visit at which time baxdrostat/placebo will be discontinued. Participants will continue open-label dapagliflozin for another 12-weeks (approximately), where reassessment of eGFR will occur for the primary efficacy endpoint. In the event of premature discontinuation of blinded study intervention, participants will continue in the study and receive open-label dapagliflozin monotherapy, unless the participant meets dapagliflozin specific discontinuation criteria, in which case all study interventions will be discontinued.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
2,554
baxdrostat tablet dapagliflozin tablet
dapagliflozin tablet placebo tablet
Research Site
Fairhope, Alabama, United States
Research Site
Phoenix, Arizona, United States
Research Site
Surprise, Arizona, United States
Research Site
Tucson, Arizona, United States
Research Site
Searcy, Arkansas, United States
Research Site
To determine whether baxdrostat/dapagliflozin is superior to dapagliflozin alone to slow CKD progression, assessed as the effect on change in eGFR over time.
Change from baseline in eGFR to post treatment.
Time frame: Baseline - 2 years + 12 weeks
To determine whether baxdrostat/dapagliflozin is superior to dapagliflozin alone at reducing UACR (urine albumin-creatinine ratio).
Change from baseline in UACR
Time frame: Baseline -16 weeks
To determine whether baxdrostat/dapagliflozin is superior to dapagliflozin alone at reducing SBP.
Change from baseline in systolic BP (blood pressure).
Time frame: Baseline -16 weeks
To determine whether baxdrostat/dapagliflozin compared with dapagliflozin alone slows CKD progression and reduces the risk of ESKD (End-stage kidney disease).
Kidney hierarchical composite endpoint.\* \*Defined as the most severe outcome of the following: 1. Death; 2. KFRT (chronic dialysis or kidney transplant); 3. Sustained GFR \< 15 mL/min/1.73 m2; 4. Sustained GFR decline from baseline of ≥ 57%; 5 Sustained GFR decline from baseline of ≥ 50%; or 6. individual change from baseline to post-treatment eGFR if none of the outcomes occurred.
Time frame: baseline - 2 years + 12 weeks
To determine whether baxdrostat/dapagliflozin compared with dapagliflozin alone slows the rate of kidney function decline after the hemodynamically-mediated acute effect on GFR (Glomerular Filtration Rate).
Change in eGFR from following randomisation.
Time frame: 8 weeks following randomisation to end of treatment
To determine whether baxdrostat/dapagliflozin is superior to dapagliflozin alone in reducing the risk of MACE
Time to the first occurrence of any of the components of the composite of: 1. CV death 2. HF with and without hospitalization 3. MI 4. Stroke
Time frame: Baseline - 24 months
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Beverly Hills, California, United States
Research Site
Canyon Country, California, United States
Research Site
Fremont, California, United States
Research Site
Fullerton, California, United States
Research Site
Lincoln, California, United States
...and 555 more locations