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
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- AstraZeneca
- 入组人数
- 11,300
- 试验地点
- 1,023
- 主要终点
- To determine if baxdrostat/dapagliflozin is superior to placebo/dapagliflozin in reducing the risk of an HF event or CV death
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Placebo controlled
入排标准
- 年龄范围
- 40 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Placebo/Dapagliflozin
Patients will receive a dose of dapagliflozin in combination with matching placebo
干预措施: Placebo and dapagliflozin (Other)
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.
干预措施: Baxdrostat and dapagliflozin (Drug)
结局指标
主要结局
To determine if baxdrostat/dapagliflozin is superior to placebo/dapagliflozin in reducing the risk of an HF event or CV death
时间窗: Event driven; Up to 38 months
Time to first occurrence of any of the components of the composite of: * Hospitalisation for HF * HF without hospitalisation * CV death
次要结局
- 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)