The main diagnosis for trial entry is T2DM with HTN and established CVD and at least one additional risk factor for developing HF.
Conditions
Interventions
BI 690517 (vicadrostat) + empa Group:BI 690517 (vicadrostat) 10 mg QD + empagliflozin 10 mg QD
Placebo + empa Group:Placebo (matching BI 690517 [vicadrostat]) + empagliflozin 10 mg QD
Sponsors
Peking University Third Hospital
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1. Aged 18 years or older at the time of signing informed consent; 2. Signed and dated written informed consent in accordance with ICH-GCP and local regulations before inclusion in this trial; 3. Male or female participants. WOCBP (see Section 4.2.2.3) must be prepared and able to use a highly effective method of contraception that meets ICH M3 (R2) criteria, i.e., a contraceptive method with an annual failure rate of less than 1% when adhered to and used correctly. A list of contraceptive methods that meet these criteria and a description of the duration of use can be found in Instructions for Participants in Section 4.2.2.3. 4. Participants with a history of HTN and receiving active medication at a possible optimal SOC according to applicable local/international guidelines (as judged by the investigator); 5. Participants with a history of T2DM and receiving active drug therapy at the best possible SOC according to applicable local/international guidelines (at the discretion of the investigator); 6. Confirmed diagnosis of CV disease and active drug therapy at the best possible SOC according to applicable local/international guidelines (as judged by the investigator). Confirmed CV disease includes at least one of the following: coronary artery disease, peripheral artery disease, or cerebrovascular disease Coronary artery disease is defined as: prior MI or coronary revascularization (e.g., CABG or PCI) or coronary angiography or other coronary imaging (eg, coronary CT angiography) showing >=50% stenosis, or history of bypass grafting Peripheral artery disease (symptomatic or non-symptomatic) is defined as: prior limb angioplasty, stenting, or bypass surgery or previous limb or foot amputation due to circulatory insufficiency or significant (> in at least 1 limb or one vascular distribution area =50%) Evidence of angiography-based or noninvasive methods of peripheral arterial stenosis or ankle-brachial index 125 pg/ml or BNP>35 pg/ml (documented within the past 6 months or at Screening (Visit 1)*) or evidence of left ventricular hypertrophy History of left ventricular hypertrophy diagnosed by echocardiography or MRI OR Evidence of left ventricular hypertrophy on 12-lead ECG according to the Sokolow-Lyon index Evidence: RV5+SV1>3.5 mV or history of atrial fibrillation or atrial flutter or ? Multivessel disease, defined as peripheral artery disease and at least one: coronary artery disease or cerebrovascular disease or within the last 3 months prior to Screening (Visit 1), Prescribed for at least 30 days with loop diuretics OR Mean systolic blood pressure at screening (Visit 1) >=140 mmHg or UACR>=200 mg/g (documented within the past 6 months or at screening (Visit 1)*) *Local laboratory assessment of BNP/NT-proBNP or UACR within 6 months prior to screening is allowed. At screening (Visit 1), NT-proBNP and UACR will be analyzed by the central laboratory;
Exclusion criteria
Exclusion criteria: 1. History of HF or hospitalization for HF or treatment of HF at Visit 1 (screening) and Visit 2 (randomization); 2. NT-proBNP >600 pg/ml in participants with sinus rhythm or >1200 pg/ml in participants with atrial fibrillation or atrial flutter at Visit 1 (analysed at the central laboratory at screening). 3. Atrial fibrillation or Atrial flutter with a resting heart rate >110 bpm documented by ECG at Visit 1 (screening); 4. Advanced untreated conduction disease (e.g. symptomatic bradycardia, sick sinus syndrome, Mobitz Type II second degree AV-block, third-degree heart block) or untreated clinically relevant ventricular arrhythmia at Visit 1 (screening); 5. Treatment with an MRA (e.g. 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. 6. 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; 7. 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 (e.g. baxdrostat) o Systemic mineralocorticoid replacement therapy (e.g. fludrocortisone); 8. Use of potassium binders (such as sodium zirconium cyclosilicate, patiromer, or sodium polystyrene sulfonate) within 4 weeks prior to Visit 1 (screening); 9. Hyperkalaemia requiring hospitalization within 12 weeks prior to Visit 1 (screening); 10. Serum potassium >5.2 mmol/L measured by the central laboratory at Visit 1 (screening) (Note: one reassessment of serum potassium is allowed during screening); 11. Impaired renal function, defined as eGFR 3x ULN as measured by central lab at Visit 1 (screening); 19. Known severe hepatic impairm
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The composite primary endpoint is the time to first event of CV death or HFE (defined as HHF or urgent HF visit). CV death includes death of undetermined cause; | — |
Secondary
| Measure | Time frame |
|---|---|
| Occurrences of all-cause hospitalisations (first and recurrent);Time to first event of CV death or HHF;Time to first event of CV death, HFE, non-fatal MI or non-fatal stroke (4-point MACE);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;Time to all-cause death;Absolute change from baseline in mean SBP [mmHg] at Week 24;Time to first occurrence of the composite outcome of Kidney disease progress, HHF, CV death;Relative change from baseline in UACR [mg/g] at Week 24; | — |
Countries
China
Contacts
Public Contactyida tang
Peking University Third Hospital
Outcome results
None listed