CTRI/2025/11/097088尚未招募3 期
A Phase III double-blind, randomised, parallel-group superiority trial to evaluate efficacy and safety of the combined use of oral vicadrostat (BI 690517) and empagliflozin compared with placebo and empagliflozin in participants with type 2 diabetes, hypertension and established cardiovascular disease
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 入组人数
- 11,800
- 试验地点
- 18
- 主要终点
- To demonstrate the superiority of the combination of vicadrostat 10 mg and empagliflozin 10 mg compared with vicadrostat-placebo and empagliflozin 10 mg for the
研究概览
简要总结
Despite recent advances in the management of type 2 diabetes mellitus (T2DM), chronic kidney disease (CKD), and hypertension (HTN), an unmet need for effective therapies remains, especially for T2DM patients with comorbid arterial HTN and established cardiovascular disease (CVD). It is hypothesized that lowering plasma aldosterone by direct inhibition of the aldosterone synthase (AS) has the potential for therapeutic benefit in reduction of CV death and heart failure events (HFE) in T2DM patients with HTN and established CVD through moderation of both aldosterone mediated MR-dependent and MR-independent action. The combination of vicadrostat and empagliflozin may achieve an
additive beneficial effect on CV outcomes in participants with established T2DM, HTN, and CVD. Therefore, the aim of the EASi™-PROTKT trial is to assess the efficacy and safety of the combination of vicadrostat 10 mg and empagliflozin 10 mg compared with vicadrostat-placebo plus empagliflozin 10 mg on occurrence of CV outcomes, mainly CV death and HFE, in addition to assessment of impact on systolic blood pressure (SBP), urine albumin creatinine ratio (UACR), first occurrence of the composite outcome of kidney disease progression, HHF or CV death, 4 pointmajor adverse cardiovascular events (4P-MACE), all-causehospitalizations, new-onset atrial fibrillation or atrial flutter (in participants without history of atrial fibrillation and atrial flutter) or CV death, and all-cause death.
研究设计
- 研究类型
- Interventional
- 分配方式
- Other
- 盲法
- Participant and Investigator Blinded
入排标准
- 年龄范围
- 18.00 Year(s) 至 99.00 Year(s)（—）
- 性别
- All
入选标准
- •At least 18 years old at time of consent
- •Signed and dated written informed consent in accordance with ICH-GCP and local legislation prior to admission to the trial.
- •Male or female participants.
- •WOCBP (see Section 4.2.2.3) must be ready and able to use highly effective methods of birth control per ICH M3 (R2) that result in a low failure rate of less than 1 percent per year when used consistently and correctly.
- •A list of contraception methods meeting these criteria and instructions on the duration of use is provided in the participant information.
- •Participants with medical history of HTN and on active pharmacological treatment according to best possible SOC in accordance with applicable local per international guidelines (according to the judgment of the investigator)
- •Participants with medical history of T2DM and on active pharmacological treatment according to best possible SOC in accordance with applicable local international guidelines (according to the judgment of the investigator).
- •Established CV disease and on active pharmacological treatment according to best possible SOC in accordance with applicable local international guidelines (according to the judgment of the investigator).
- •Established CV disease includes at least one of the following: coronary artery disease, or peripheral artery disease, or cerebrovascular disease.
排除标准
- •History of HF or hospitalization for HF or treatment of HF at Visit 1 (screening) and Visit 2 (randomization)
- •NT-proBNP more than 600 pg per ml in participants with sinus rhythm or more than 1200 pg per ml in participants with atrial fibrillation or atrial flutter at Visit 1 (analysed at the central laboratory at screening)
- •Atrial fibrillation or Atrial flutter with a resting heart rate more than 110 bpm documented by ECG at Visit 1 (screening)
- •Treatment with an MRA (example.
- •spironolactone, eplerenone, finerenone) within 2 weeks prior to Visit 1 (screening) or requiring such treatment before Visit 2 (randomisation) or planned during the trial based on the judgment of the investigator.
- •Treatment with MRA should not be interrupted with the intention of enrolment into the study
- •Treatment with amiloride or other potassium-sparing diuretic within 2 weeks prior to Visit 1 (screening) or requiring such treatment before Visit 2 (randomisation) or planned during the trial based on the judgment of the investigator
- •Receiving the following treatments at Visit 1 (screening) or requiring such treatment before Visit 2 (randomisation), or planned during the trial: o A direct renin inhibitor (e.g. aliskiren) o More than one ACEi and or ARB (including ARNi) used simultaneously o Other aldosterone synthase inhibitors (example baxdrostat) o Systemic mineralocorticoid replacement therapy (example.
- •fludrocortisone)
- •Use of potassium binders (such as sodium zirconium cyclosilicate, patiromer, or sodium polystyrene sulfonate) within 4 weeks prior to Visit 1 (screening)
- •Hyperkalaemia requiring hospitalization within 12 weeks prior to Visit 1 (screening)
- •Serum potassium more than 5.2 mmol per L measured by the central laboratory at Visit 1 (screening) (Note: one reassessment of serum potassium is allowed during screening)
- •Impaired renal function, defined as eGFR less than 20 mL per min per 1.73 m2 (CKD-EPI) at Visit 1 (screening) measured by the central laboratory, or on renal replacement therapy.
- •(Note: one reassessment of eGFR is allowed during screening)
- •Known adrenal insufficiency (example Addison disease) or Cushings syndrome
- •Symptomatic hypotension and or a mean SBP less than 100 mmHg at Visit 1 (screening) or up to and including Visit 2 (randomisation).
- •Mean SBP more than equals to 180 mmHg or mean DBP more than equals to 120 mmHg at Visit 1 (screening) or Visit 2 (randomisation).
- •MI or stroke or transient ischemic attack or acute inflammatory heart disease, such as acute myocarditis or major surgery (major according to the investigators assessment), within 12 weeks prior to Visit 1 (screening) and until Visit 2 (randomisation) or planned major elective surgery (e.g. hip replacement, CABG)
- •Percutaneous vascular intervention or any angiography using iodinated contrast agents in the 1 week prior to Visit 2 (randomisation)
- •Known severe valvular heart disease (obstructive or regurgitant) except mitral regurgitation secondary to left ventricular dilatation, as per investigators judgement, or valvular heart disease scheduled for surgical or invasive procedures at Visit 1 (screening), or anticipated invasive treatment during the study
- •ALT or AST more than 3 times ULN as measured by central lab at Visit 1 (screening)
- •Known severe hepatic impairment (example.
- •Child Pugh class C cirrhosis)
- •Gastrointestinal surgery or gastrointestinal disorder that could interfere with trial medication absorption in the investigators opinion example.
- •intestinal resection, inflammatory bowel disease, currently active gastritis, pancreatitis
- •Type 1 diabetes mellitus or history of other autoimmune causes of diabetes mellitus (example.
- •History of ketoacidosis within 5 years prior to Visit 1 (screening) or until Visit 2 (randomisation)
- •Any documented active or suspected malignancy or history of malignancy within 5 years prior to Visit 1 (screening), except appropriately treated basal cell carcinoma of the skin, in situ carcinoma of uterine cervix or low risk prostate cancer (patients with pre-treatment PSA less than 10 ng per mL and biopsy Gleason score of less than equals to 6 and clinical stage T1c or T2a)
- •Participants who must or wish to continue the intake of restricted medications (see Section 4.2.2.1) or any drug considered likely to interfere with the safe conduct of the trial
- •Participants not expected to comply with the protocol requirements or not expected to complete the trial as scheduled (e.g. chronic alcohol or drug abuse or any other condition that, in the investigators opinion, makes the participant an unreliable trial participant)
- •Currently enrolled in another investigational device or drug trial, or less than 30 days from Visit 1 (screening) since ending another investigational device or drug trial(s) or receiving other investigational treatment(s).
- •Women who are pregnant, breastfeeding, or plan to become pregnant while in the trial
- •Any condition not covered by any of the other exclusion criteria which, in the investigators opinion, might jeopardise the participants safety or compliance with the protocol.
- •Any vulnerable person (defined as: pregnant or breastfeeding women; persons deprived of their liberty; minors; persons that may have insufficient power, intelligence, education, resources, strength, or other needed attributes to protect their own interests; or unable to explicitly give consent), as per local regulation.
- •Intolerance or known allergy or hypersensitivity to vicadrostat or empagliflozin or other SGLT2 inhibitors and or any of the excipients (including lactose).
结局指标
主要结局
To demonstrate the superiority of the combination of vicadrostat 10 mg and empagliflozin 10 mg compared with vicadrostat-placebo and empagliflozin 10 mg for the
时间窗: week 24
time to first CV death, hospitalisation for heart failure (HHF), or urgent heart failure (HF) visit in participants with T2DM with HTN and established CVD
时间窗: week 24
次要结局
- to demonstrate the superiority of the combination of vicadrostat 10 mg and empagliflozin 10 mg compared with vicadrostat-placebo and empagliflozin 10 mg for the(time to first event of CV death or HHF, absolute change from baseline in mean SBP at Week 24, relative change from baseline in UACR at Week 24, time to first occurrence of the composite outcome of kidney disease progression or HHF or CV death, time to first event of 4P-MACE, occurrences of all-cause hospitalisations (first and recurrent), time to first event of new-onset atrial fibrillation or atrial flutter (in participants without history of atrial fibrillation and atrial flutter) or CV death, and time to all-cause death)
研究者
研究点 (18)
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