Studies of Heart & Kidney Protection with BI 690517 in combination with empagliflozin: A multicenter, international, randomized, double blind, placebo-controlled clinical trial of the aldosterone synthase inhibitor BI 690517 in combination with empagliflozin in patients with chronic kidney disease.
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 11,000
- 试验地点
- 36
- 主要终点
- Kidney disease progression (defined as kidney failure†or a sustained ≥40% decline in eGFR from randomization); or
研究概览
简要总结
Chronic kidney disease (CKD) affects over 850 million individuals globally, representing a substantial health burden due to its progressive nature and lack of definitive treatments. CKD often progresses to end-stage renal disease, necessitating dialysis or kidney transplantation, and significantly increases the risk of cardiovascular morbidity and mortality. Building on the EMPA-KIDNEY trial, which demonstrated the efficacy of empagliflozin in reducing the risk of kidney failure, dialysis, or cardiovascular death in CKD patients, the EASi-KIDNEY trial aims to evaluate the potential of BI 690517, an aldosterone synthase inhibitor, in further slowing the progression of CKD. Elevated aldosterone levels contribute to organ damage, hypertension, CKD, and heart failure, with BI 690517 targeting aldosterone synthase to inhibit aldosterone synthesis.
The EASi-KIDNEY trial is a phase III, multicenter, international, randomized, double-blind, placebo-controlled clinical study designed to assess the efficacy of BI 690517 in combination with empagliflozin in preventing CKD progression, reducing heart failure incidence, and decreasing cardiovascular-related mortality. The trial aims to enroll approximately 11,000 participants, including those with and without type 2 diabetes.
Participants will be randomly assigned to receive either BI 690517 10mg daily or a matching placebo, both in conjunction with empagliflozin 10mg daily. The primary endpoints include time to the first occurrence of kidney disease progression (defined as kidney failure or a sustained ≥40% decline in eGFR from baseline), hospitalization for heart failure, or cardiovascular death. Secondary endpoints encompass the annual rate of change in eGFR, with pooled analysis key outcomes covering kidney failure, hospitalization for heart failure, cardiovascular death, all-cause hospitalization, and all-cause mortality.
The study includes an 8-week run-in phase where participants receive placebo or BI 690517, followed by the initiation of empagliflozin 10mg. Participants will attend four clinic appointments in the first six months, followed by biannual visits thereafter. The trial duration is event-driven, continuing until the required number of participants have experienced their first primary outcome event. The Steering Committee will periodically review and may adjust the minimum number of primary outcome events based on interim analyses and adherence to ensure a robust assessment of BI 690517’s efficacy. This comprehensive evaluation is anticipated to span 3-4 years.
In India, the trial aims to enroll 1,250 participants across 21 sites, contributing to the global effort to establish a new therapeutic paradigm for CKD management by providing critical data on the combined use of BI 690517 and empagliflozin in mitigating CKD progression and associated cardiovascular risks.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 盲法
- Participant, Investigator, Outcome Assessor and Date-entry Operator 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
- •Age is ≥18 years at Screening;
- •There is evidence of CKD at risk of kidney disease progression
- •A local investigator judges that the potential participant: a.
- •Neither requires an ASi or MRA, nor that such treatment is definitely inappropriate (i.e. the uncertainty principle) b.
- •Is treated with an investigator-judged clinically appropriate dose of a RAS inhibitor, unless such treatment is either not tolerated or not indicated; c.
- •Can initiate empagliflozin 10mg daily when not already treated, or are able to switch to empagliflozin 10mg daily where already treated with a different SGLT inhibitor.
排除标准
- •1.Blood potassium of more than 5.2 mmolLs at screening visit 2.Blood ALT or AST More than 3x ULN at Screening visit 3.Known liver cirrhosis 4.On dialysis, functioning kidney transplant, or scheduled living donor transplant 5.Treated with new immunosuppression therapy for new (or relapse/flare of pre-existing) kidney disease within the last 60 days 6.Receiving more than one RAS inhibitor (i.e. on dual therapy with two of an ACEi, ARB or direct renin inhibitor) 7.Currently treated with an MRA (e.g. spironolactone, eplerenone, finerenone) 8.Currently treated with systemic mineralocorticoid replacement therapy (e.g. fludrocortisone) 9.Known Cushing’s syndrome 10.Known adrenal cortisol insufficiency 11.Hypersensitivity (i.e. allergic reaction or anaphylaxis) to ASi 12.Use of an investigational medicinal product in the 30 days prior to Screening visit 13.Symptomatic hypotension, or systolic blood pressure less than 100 or more than 180 mmHg (using local blood pressure machine) 14.Known to be poorly compliant with clinic visits or prescribed medication 15.History that might limit the individual’s ability to report medical information reliably (e.g. known dementia, recent history of alcohol or substance misuse, or difficulty answering Screening visit questions); or limit ability to take study treatments for the duration of the study (e.g. terminal respiratory disease; history of invasive cancer or evidence of cancer spread within the last 3 years [excluding low-grade canceru]) 16.Current pregnancy, lactation or women of childbearing potential, unless using highly effective contraception 17.Hypersensitivity (i.e. allergic reaction or anaphylaxis) to SGLT2 inhibitor 18.Type 1 diabetes mellitus 19.Ketoacidosis in last 5 years 20.Polycystic kidney disease.
结局指标
主要结局
Kidney disease progression (defined as kidney failure†or a sustained ≥40% decline in eGFR from randomization); or
时间窗: From Randomisation to End of the study
Hospitalization for heart failure; or
时间窗: From Randomisation to End of the study
Cardiovascular death
时间窗: From Randomisation to End of the study
次要结局
- 1.Annual rate of change in eGFR from 3 months until last scheduled visit (i.e. chronic eGFR slope)(2.Time to first event of kidney failure, hospitalization for heart failure or cardiovascular death)
研究者
Dr Vivekanand Jha
George Institute Services India Pvt Ltd