Phase III Study Investigating Heart Failure and Cardiovascular Death With Baxdrostat in Combination With Dapagliflozin
Purpose
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.
Condition
- Heart Failure
Eligibility
- Eligible Ages
- Over 40 Years
- Eligible Sex
- All
- Accepts Healthy Volunteers
- No
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
Study Design
- Phase
- Phase 3
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel Assignment
- Primary Purpose
- Prevention
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
- Masking Description
- Placebo controlled
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental Baxdrostat/Dapagliflozin |
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. |
|
|
Experimental Placebo/Dapagliflozin |
Patients will receive a dose of dapagliflozin in combination with matching placebo |
|
Recruiting Locations
Research Site
Birmingham, Alabama 35205
Birmingham, Alabama 35205
Research Site
Centreville, Alabama 35042
Centreville, Alabama 35042
Research Site
Fairhope, Alabama 36532
Fairhope, Alabama 36532
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Mobile, Alabama 36608
Mobile, Alabama 36608
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Vestavia Hills, Alabama 35216
Vestavia Hills, Alabama 35216
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Gilbert, Arizona 85296
Gilbert, Arizona 85296
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Glendale, Arizona 85308
Glendale, Arizona 85308
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Tempe, Arizona 85283
Tempe, Arizona 85283
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Tucson, Arizona 85712
Tucson, Arizona 85712
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Huntington Beach, California 92648
Huntington Beach, California 92648
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Inglewood, California 90301
Inglewood, California 90301
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La Jolla, California 92037
La Jolla, California 92037
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Lincoln, California 95648
Lincoln, California 95648
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Loma Linda, California 92357
Loma Linda, California 92357
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Los Angeles, California 90035
Los Angeles, California 90035
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Sacramento, California 95841
Sacramento, California 95841
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San Diego, California 92120
San Diego, California 92120
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San Dimas, California 91773
San Dimas, California 91773
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Santa Maria, California 93454
Santa Maria, California 93454
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Thousand Oaks, California 91360
Thousand Oaks, California 91360
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Aurora, Colorado 80012
Aurora, Colorado 80012
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Englewood, Colorado 80110
Englewood, Colorado 80110
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Bridgeport, Connecticut 06606
Bridgeport, Connecticut 06606
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Stamford, Connecticut 06905
Stamford, Connecticut 06905
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Waterbury, Connecticut 06708
Waterbury, Connecticut 06708
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Crystal River, Florida 34429
Crystal River, Florida 34429
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Fort Lauderdale, Florida 33316
Fort Lauderdale, Florida 33316
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Fort Myers, Florida 33912
Fort Myers, Florida 33912
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Hialeah, Florida 33012
Hialeah, Florida 33012
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Jacksonville, Florida 32216
Jacksonville, Florida 32216
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Lakeland, Florida 33813
Lakeland, Florida 33813
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Ocoee, Florida 34761
Ocoee, Florida 34761
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Palmetto Bay, Florida 33157
Palmetto Bay, Florida 33157
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Saint Augustine, Florida 32086
Saint Augustine, Florida 32086
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Albany, Georgia 31707
Albany, Georgia 31707
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Atlanta, Georgia 30303
Atlanta, Georgia 30303
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Canton, Georgia 30114
Canton, Georgia 30114
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Columbus, Georgia 31904
Columbus, Georgia 31904
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Cordele, Georgia 31015
Cordele, Georgia 31015
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Suwanee, Georgia 30024
Suwanee, Georgia 30024
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Woodstock, Georgia 30189
Woodstock, Georgia 30189
Research Site
Idaho Falls, Idaho 83404
Idaho Falls, Idaho 83404
Research Site
Champaign, Illinois 61822
Champaign, Illinois 61822
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Chicago, Illinois 60616
Chicago, Illinois 60616
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Chicago, Illinois 60621
Chicago, Illinois 60621
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Chicago, Illinois 60631
Chicago, Illinois 60631
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Gurnee, Illinois 60031
Gurnee, Illinois 60031
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Island Lake, Illinois 60042
Island Lake, Illinois 60042
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Park Ridge, Illinois 60068
Park Ridge, Illinois 60068
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Indianapolis, Indiana 46202
Indianapolis, Indiana 46202
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Munster, Indiana 46321
Munster, Indiana 46321
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Richmond, Indiana 47374
Richmond, Indiana 47374
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South Bend, Indiana 46617
South Bend, Indiana 46617
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El Dorado, Kansas 67042
El Dorado, Kansas 67042
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Lenexa, Kansas 66219
Lenexa, Kansas 66219
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Newton, Kansas 67114
Newton, Kansas 67114
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Lexington, Kentucky 40509
Lexington, Kentucky 40509
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Owensboro, Kentucky 42301
Owensboro, Kentucky 42301
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Paducah, Kentucky 42001
Paducah, Kentucky 42001
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Alexandria, Louisiana 71303
Alexandria, Louisiana 71303
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Baltimore, Maryland 21229
Baltimore, Maryland 21229
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Beltsville, Maryland 20705
Beltsville, Maryland 20705
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Lutherville-Timonium, Maryland 21093
Lutherville-Timonium, Maryland 21093
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Potomac, Maryland 20854
Potomac, Maryland 20854
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Boston, Massachusetts 02115
Boston, Massachusetts 02115
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New Bedford, Massachusetts 02740
New Bedford, Massachusetts 02740
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Roslindale, Massachusetts 02131
Roslindale, Massachusetts 02131
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Farmington Hills, Michigan 48336
Farmington Hills, Michigan 48336
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Flint, Michigan 48532
Flint, Michigan 48532
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Troy, Michigan 48098
Troy, Michigan 48098
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Mankato, Minnesota 56001
Mankato, Minnesota 56001
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Columbia, Missouri 65201
Columbia, Missouri 65201
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Kansas City, Missouri 64111
Kansas City, Missouri 64111
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Kansas City, Missouri 64151
Kansas City, Missouri 64151
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St Louis, Missouri 63136
St Louis, Missouri 63136
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Missoula, Montana 59804
Missoula, Montana 59804
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Norfolk, Nebraska 68701
Norfolk, Nebraska 68701
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Omaha, Nebraska 68134
Omaha, Nebraska 68134
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Carson City, Nevada 89706
Carson City, Nevada 89706
Research Site
Pennington, New Jersey 08534
Pennington, New Jersey 08534
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Somerset, New Jersey 08873
Somerset, New Jersey 08873
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Albuquerque, New Mexico 87102
Albuquerque, New Mexico 87102
Research Site
Albuquerque, New Mexico 87108
Albuquerque, New Mexico 87108
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Albany, New York 12208
Albany, New York 12208
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Brooklyn, New York 11201
Brooklyn, New York 11201
Research Site
Brooklyn, New York 11220
Brooklyn, New York 11220
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Massapequa, New York 11758
Massapequa, New York 11758
Research Site
Queens Village, New York 11428
Queens Village, New York 11428
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Charlotte, North Carolina 28287
Charlotte, North Carolina 28287
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Durham, North Carolina 27701
Durham, North Carolina 27701
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Fayetteville, North Carolina 28304
Fayetteville, North Carolina 28304
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Monroe, North Carolina 28112
Monroe, North Carolina 28112
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New Bern, North Carolina 28562
New Bern, North Carolina 28562
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Raleigh, North Carolina 27607
Raleigh, North Carolina 27607
Research Site
Rocky Mount, North Carolina 27804
Rocky Mount, North Carolina 27804
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Fargo, North Dakota 58104
Fargo, North Dakota 58104
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Beavercreek, Ohio 45431
Beavercreek, Ohio 45431
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Canton, Ohio 44718
Canton, Ohio 44718
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Cincinnati, Ohio 45219
Cincinnati, Ohio 45219
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Cincinnati, Ohio 45220
Cincinnati, Ohio 45220
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Columbus, Ohio 43215
Columbus, Ohio 43215
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Maumee, Ohio 43537
Maumee, Ohio 43537
Research Site
Oklahoma City, Oklahoma 73111
Oklahoma City, Oklahoma 73111
Research Site
Oklahoma City, Oklahoma 73120
Oklahoma City, Oklahoma 73120
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Camp Hill, Pennsylvania 17011
Camp Hill, Pennsylvania 17011
Research Site
Horsham, Pennsylvania 19044
Horsham, Pennsylvania 19044
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Philadelphia, Pennsylvania 19114
Philadelphia, Pennsylvania 19114
Research Site
Scottdale, Pennsylvania 15683
Scottdale, Pennsylvania 15683
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Smithfield, Pennsylvania 15478
Smithfield, Pennsylvania 15478
Research Site
Fort Mill, South Carolina 29715
Fort Mill, South Carolina 29715
Research Site
Mt. Pleasant, South Carolina 29464
Mt. Pleasant, South Carolina 29464
Research Site
North Charleston, South Carolina 29405
North Charleston, South Carolina 29405
Research Site
Spartanburg, South Carolina 29301
Spartanburg, South Carolina 29301
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Cleveland, Tennessee 37312
Cleveland, Tennessee 37312
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Morristown, Tennessee 37813
Morristown, Tennessee 37813
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Nashville, Tennessee 37203
Nashville, Tennessee 37203
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Austin, Texas 78704
Austin, Texas 78704
Research Site
Beaumont, Texas 77702
Beaumont, Texas 77702
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Dallas, Texas 75390-9015
Dallas, Texas 75390-9015
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Duncanville, Texas 75137
Duncanville, Texas 75137
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Houston, Texas 77084
Houston, Texas 77084
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Houston, Texas 77089
Houston, Texas 77089
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McAllen, Texas 78501
McAllen, Texas 78501
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McAllen, Texas 78503
McAllen, Texas 78503
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Mesquite, Texas 75149
Mesquite, Texas 75149
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Paris, Texas 75462
Paris, Texas 75462
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San Antonio, Texas 78257
San Antonio, Texas 78257
Research Site
Stephenville, Texas 76401
Stephenville, Texas 76401
Research Site
Sugar Land, Texas 77479
Sugar Land, Texas 77479
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Tomball, Texas 77375
Tomball, Texas 77375
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Weslaco, Texas 78596
Weslaco, Texas 78596
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Woodway, Texas 76712
Woodway, Texas 76712
Research Site
Clearfield, Utah 84015
Clearfield, Utah 84015
Research Site
Roy, Utah 84067
Roy, Utah 84067
Research Site
Burke, Virginia 22015
Burke, Virginia 22015
Research Site
Charlottesville, Virginia 22911
Charlottesville, Virginia 22911
Research Site
Falls Church, Virginia 22042
Falls Church, Virginia 22042
Research Site
Norfolk, Virginia 23502
Norfolk, Virginia 23502
Research Site
Redmond, Washington 98052
Redmond, Washington 98052
Research Site
Renton, Washington 98057
Renton, Washington 98057
Research Site
Kingwood, West Virginia 26537
Kingwood, West Virginia 26537
Research Site
Morgantown, West Virginia 26505
Morgantown, West Virginia 26505
More Details
- Status
- Recruiting
- Sponsor
- AstraZeneca
Study Contact
AstraZeneca Clinical Study Information Center1-877-240-9479
information.center@astrazeneca.com