CTRI/2025/02/081078招募中3 期
A Phase III double-blind randomized parallel-group superiority trial to evaluate efficacy and safety of the combined use of oral BI 690517 and empagliflozin compared with placebo and empagliflozin in participants with symptomatic heart failure (HF: NYHA II-IV) and left ventricular ejection fraction (LVEF) more than equals to 40 percent.
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 6,000
- 试验地点
- 12
- 主要终点
- To demonstrate the superiority of the combination of BI 690517 10 mg and empagliflozin 10 mg compared with placebo and empagliflozin 10 mg for the time to first CV death or HHF in participants with HF and LVEF more than equals to 40%, based on a hazard ratio
研究概览
简要总结
This trial is a double-blind, randomised, parallel-group, multi-centre, Phase III clinical trial investigating the combined use of oral BI 690517 and empagliflozin compared with placebo and empagliflozin in participants with symptomatic HF and LVEF ≥40%.
The treatment period duration will be based on accrual of primary endpoint events.
Participants, investigators, and everyone involved in trial conduct or analysis, or with any other interest in this double-blind trial, will remain blinded with regard to the randomised treatment assignments until after database lock. Emergency unblinding will be available to the investigator via the IRT.
Overall sample size: approx. 6000*
Sample size for each group (n = 2 groups): approx. 3000 participants per group
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
- •Eligible participants will have a diagnosis of HF with LVEF 40 percent and meet eligibility criteria below.
- •At least 18 years old and at least of the legal age of consent in countries where it is greater than 18 years
- •Signed and dated written informed consent in accordance with ICH-GCP and local legislation prior to admission to the trial
- •Male or female participants.
- •Women of childbearing potential1 must be ready and able to use highly effective methods of birth control per International Conference on Harmonisation (ICH) M3 (R2) that result in a low failure rate of less than 1percent per year when used consistently and correctly.
- •A list of contraception methods meeting these criteria and instructions on the duration of their use is provided in the participant information.
- •Chronic HF diagnosed at least 3 months before Visit 1, and in NYHA class II-IV at Visit 1, with LVEF 40 percent per local reading (obtained by echocardiography, radionuclide ventriculography, invasive angiography, MRI, or CT).
- •A historical LVEF may be used if it was measured within 12 months prior to Visit 1, or the LVEF may be measured after study consent has been obtained and before Visit 2 (if several values are available, the most recent one should be considered)
- •Presence of structural heart abnormality (confirmed by any imaging modality; i.e. echocardiography at Visit 1, as defined by left ventricular hypertrophy or left atrial enlargement) (see Appendix 10.3).
- •Historical imaging may be used if performed within 12 months prior to Visit 1, or imaging may be completed after study consent has been obtained and before Visit
- •If several values are available, the most recent one should be considered.
- •At least one of the following: (a) Currently treated with diuretic therapy e.g. loop diuretics or thiazides, and on a stable dose for at least 1 week prior to Visit 1 (b) Documented hospitalisation for HF within 6 months prior to Visit 1 (c) Elevated NT-proBNP at Visit 1, analysed at the central laboratory at Visit 1 (a).
- •in participants without Afib or Aflutter (at Visit 1 ECG): 900 pg/mL (b).
- •for participants with Afib or Aflutter (at Visit 1 ECG): 1800 pg/mL
- •Participants must be treated according to best possible SOC in accordance with applicable HF local/international guidelines (according to the judgment of the investigator) Additional inclusion criteria apply to the optional accelerometry substudy: (1) Willing and able to provide informed consent for substudy participation; and (2) Capable of ambulation, with or without a walking aid.
- •Elevated NTproBNP at Visit 1, analysed at the central laboratory at Visit 1 a) n participants with BMI less than 27 kg/m2 more than equals to 300 pg/mL for participants without Afib or Aflutter (at Visit 1 ECG) and more than equals to 900 pg/mL for participants with Afib or Aflutter (at Visit 1 ECG), (b) in participants with BMI more than equals to 27 kg/m2 to less than 35 kg/m2 more than equals to 220 pg/mL for participants without Afib or Aflutter (at Visit 1 ECG) and more than equals to 660 pg/mL for participants with Afib or Aflutter (at Visit 1 ECG) (c) in participants with BMI more than equals to 35 kg/m2 more than equals to 125 pg/mL for participants without Afib or Aflutter (at Visit 1 ECG) and more than equals to 375 pg/mL for participants with Afib or Aflutter (at Visit 1 ECG).
排除标准
- •Treatment with an MRA (e.g. spironolactone, eplerenone, finerenone) within 14 days prior to Visit 1 or requiring such treatment before 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
- •Receiving the following treatments: a.
- •a direct renin inhibitor (e.g. aliskiren) at Visit 2 b.
- •more than one ACEI, ARB or ARNI, or two simultaneously at Visit 2 c.
- •Acute decompensated HF requiring hospitalisation or i.v. therapy including diuretics, or i.v. inotropes or i.v. vasodilators, mechanical support (such as an intra-aortic balloon pump, endotracheal intubation, mechanical ventilation, any ventricular assist device), or IV natriuretic peptide (e.g. nesiritide) within the past 7 days prior to Visit 2
- •MI, CVA, TIA, stroke, coronary artery bypass graft surgery/CABG, heart valve surgery or any other major surgery (major according to the investigator assessment) within 90 days prior to Visit 1, or scheduled for major elective surgery (e.g. hip replacement, coronary artery bypass graft surgery/CABG)
- •Heart transplant recipient, awaiting heart transplant, or currently implanted LVAD
- •Known cardiomyopathy based on infiltrative diseases (e.g. amyloidosis), accumulation diseases (e.g. haemochromatosis, Fabry disease), muscular dystrophies, hypertrophic obstructive cardiomyopathy or known pericardial constriction, or cardiomyopathy with potentially reversible cause such as stress or peripartum cardiomyopathy or cardiomyopathy induced by chemotherapy within the 12 months prior to Visit 1 and until Visit 2
- •Acute inflammatory heart disease, such as acute myocarditis, within the 90 days preceding prior to Visit 1and until Visit 2
- •Known severe valvular heart disease (obstructive or regurgitant), as per investigator judgment, or valvular heart disease scheduled for surgical or invasive procedures at Visit 1, or anticipated invasive treatment during the study
- •Atrial fibrillation or Atrial flutter with a resting heart rate more than 110 bpm documented by ECG at Visit 1
- •Untreated clinically relevant ventricular arrhythmia without an ICD at Visit 1 and/or Visit 2
- •Unless managed with an implanted pacemaker: symptomatic bradycardia, sick sinus syndrome, Mobitz Type II second degree AV-Block, or third-degree heart block
- •Implantation of ICD or CRT within 3 months prior to Visit 1 or until Visit 2
- •SBP more than equals to 180 mmHg at Visit 1 or Visit
- •If SBP more than 150 mmHg and less than 180 mmHg at Visit 1, the participant should be receiving at least 3 antihypertensive drugs.
- •Severe chronic pulmonary disease according to investigators judgment: e.g. with known FEV1 less than 50 percent or need for home oxygen, primary pulmonary arterial hypertension, or chronic obstructive pulmonary disease exacerbation requiring i.v. or chronic oral steroids within 3 months prior to Visit 1 or until Visit 2
- •Serum potassium more than 5.2 mmol/L measured by the central laboratory at Visit 1 (Note one reassessment of serum potassium is allowed during screening)
- •ALT or AST more than 3x ULN at Visit 1 or known hepatic cirrhosis (Child Pugh C), or other liver disease causing severe impaired liver function, according to investigators judgment
- •Impaired renal function, defined as eGFR less than 20 mL/min/1.73 m2 (CKD-EPI) as determined at Visit 1 by the central laboratory, or on renal replacement therapy.
- •(Note: one reassessment of eGFR is allowed during screening)
- •Haemoglobin (Hb) less than 9 g/dL as determined at Visit 1 by the central laboratory
- •Known adrenal insufficiency (e.g. Addison disease) or Cushing syndrome
- •History of ketoacidosis within 5 years prior to Visit 1 or until Visit 2
- •Gastrointestinal surgery or gastrointestinal disorder that could interfere with trial medication absorption in the investigators opinion
- •Type 1 diabetes mellitus, or history of other autoimmune causes of diabetes mellitus (e.g. LADA)
- •Any documented active or suspected malignancy or history of malignancy within 5 years prior to Visit 1, except appropriately treated basal cell carcinoma of the skin, in situ carcinoma of uterine cervix or low risk prostate cancer (participants with pre treatment PSA less than 10 ng/mL and biopsy Gleason score of more 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
- •Currently enrolled in another investigational device or drug trial, or less than 30 days since ending another investigational device or drug trial(s), or receiving other investigational treatment(s).
- •Those participating in a purely observational trial will not be excluded.
- •Chronic alcohol or drug abuse or any condition that, in the investigators opinion, makes them an unreliable trial participant or unlikely to complete the trial
- •Women who are pregnant, nursing, or who plan to become pregnant while in the trial
- •Intolerance or known allergy or hypersensitivity to BI 690517 or empagliflozin or other SGLT2 inhibitors and/or any of the excipients (including lactose).
- •Any condition not covered by any of the other exclusion criteria, including abnormal laboratory values, which in the investigators opinion, might jeopardise the participants safety or compliance with the protocol.
结局指标
主要结局
To demonstrate the superiority of the combination of BI 690517 10 mg and empagliflozin 10 mg compared with placebo and empagliflozin 10 mg for the time to first CV death or HHF in participants with HF and LVEF more than equals to 40%, based on a hazard ratio
时间窗: Time to first event of CV death or HHF. Death and HHF will be categorised by the investigator according to pre-specified criteria
次要结局
- to demonstrate the superiority of the combination of BI 690517(10 mg & empagliflozin 10 mg to placebo & empagliflozin 10 mg for the time to first event of CV death, HHF or urgent HF visit, the total number of HHF (first & recurrent), the absolute change from baseline in KCCQ-TSS at Week 32 [R17-2666], the time to CV death & the time to all-cause mortality)
研究者
研究点 (12)
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