CTRI/2024/12/077518尚未招募3 期
A Phase III, Randomised, Double-blind Study to Evaluate the Effect of Balcinrenone /Dapagliflozin, Compared with Dapagliflozin, on the Risk of Heart Failure Events and Cardiovascular Death in Patients with Heart Failure and Impaired Kidney Function (BalanceD-HF)
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 入组人数
- 4,800
- 试验地点
- 24
- 主要终点
- To determine whether balcinrenone/dapagliflozin is superior to dapagliflozin in reducing the risk of CV death, and HF events with and without hospitalisation
研究概览
简要总结
This is the first long-term study evaluating the efficacy and safety of the combination of balcinrenone and dapagliflozin in patients with HF and impaired kidney function.
The primary hypothesis of the study is that balcinrenone/dapagliflozin (either 15 mg/10 mg or 40 mg/10 mg, once daily) compared with dapagliflozin 10 mg will reduce the risk of CV death, and HF event with and without hospitalisation in adults with chronic HF and impaired kidney function. The selection and adjudication of the primary and secondary endpoints are consistent with the standard for HF outcome studies (Abraham et al 2020).
The primary objective will be addressed by the intention-to-treat principle (ICH-E9(R1) 2019), which assesses differences in outcomes between treatment groups over the period from randomisation until the PACD to reflect the effect of the initially assigned randomised IMP, irrespective of concomitant treatment, or discontinuation of IMP, and in the absence of death due to non-CV causes, withdrawal of consent, and lost-to-follow-up.
The study will evaluate general safety and tolerability of balcinrenone/dapagliflozin compared with dapagliflozin with special attention to hyperkalaemia, renal events/AKI, and hypotension. The visit frequency and safety monitoring are aligned with recommendations when initiating MRAs and dapagliflozin (McDonagh et al 2021).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 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
- •Age 1 Participant must be ≥ 18 years old, at the time of signing the informed consent Type of Participant and Disease Characteristics 2 Documented diagnosis of symptomatic HF (NYHA functional Class II to IV), present before the last event.
- •3 Having had a recent HF event†, defined as either: a.
- •A hospitalisation primarily for a HF indication including signs and symptoms of congestions and use of parenteral medications for HF during admission within 6 months prior to randomisation, OR b.
- •An urgent HF visit with outpatient parenteral medications for HF within 6 months prior to randomisation, OR c.
- •Currently hospitalised due to worsening of chronic HF, but with none of the following within the last 24 hours of randomisation: i.
- •Invasive or non-invasive ventilation ii.
- •IV vasopressor, IV vasodilator use including nitrates or IV inotropes iii.
- •Increase in dose of IV diuretics 4 Have a LVEF value from an assessment within the last 12 months.
- •Participants not assessed within that timeframe may undergo a local echocardiogram at the time of enrolment.
- •Participant who have undergone coronary revascularisation (percutaneous coronary intervention or coronary artery bypass grafting), valve repair/replacement or implantation of a cardiac resynchronisation therapy device or any other surgical, device that might improve LVEF must have had a measurement of LVEF at least 3 months after the intervention in order to be eligible.
- •5 Managed with SoC therapy for HF and impairmed kidney function according to local guidelines (with the exception of MRA), with or without SGLT2 inhibitors.
- •SGLT2 inhibitors can be taken up to the day before randomisation (ie, start of double-blind treatment).
- •Participants on SGLT2i prior to randomisation will switch to blinded study therapy at randomisation and will discontinue the SGLT2i they were prescribed before the randomisation.
- •6 Not taking an MRA, for one of the following reasons: a.
- •Mineralocorticoid receptor antagonist not indicated due to LVEF of greater than 40% (HFmrEF and HFpEF) b.
- •Mineralocorticoid receptor antagonist not recommended or contraindicated due to low eGFR (as per local guidelines) c.
- •History of MRA adverse reaction/intolerance from approved MRA; Hyperkalaemia, Worsening kidney function, Hypotension, Hormonal side effects (such as gynecomastia, erectile dysfunction) d.
- •Specific concerns for adverse reactions from approved MRAs; hyperkalaemia, worsening kidney function, hypotension, hormonal side effects (such as gynecomastia, erectile dysfunction) b.
- •Specific concerns for adverse reactions from approved MRAs; hyperkalaemia, worsening kidney function, hypotension, hormonal side effects (such as gynecomastia, erectile dysfunction) 7 An eGFR greater than or equal to 20 to Less than 60 mL/min/1.73 m2, from Visit
- •8 Serum or plasma potassium greater than or equal to 3.5 mmol/L and less than or equal to 5.0 mmol/L at Visit 1 9 NT-proBNP must be greater than 300 pg/mL at Visit 1 (greater than 600 pg/mL if concomitant atrial fibrillation or atrial flutter at Visit 1).
- •If available, a local laboratory result (serum or plasma) from Less than 30 days prior to Visit 1 can be used for inclusion.
- •For participants randomised while hospitalised, any local value must have been collected during the index event.
- •For participants randomised while hospitalised and where NT-proBNP is not available in local laboratory results used to determine eligibility, BNP result (serum or plasma) must be greater than 100 pg/mL if sinus rhythm (greater than 300 pg/mL if concomitant atrial fibrillation at Visit 1).
- •10 Contraceptive use by females should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
- •Females not of childbearing potential are defined as females who are either permanently sterilised (hysterectomy, bilateral oophorectomy, or bilateral salpingectomy), or who are postmenopausal.
- •Females will be considered postmenopausal if they have been amenorrhoeic for 12 months prior to the planned date of randomisation without an alternative medical cause.
- •The following age-specific requirements apply: b.
- •Females Less than 50 years old would be considered postmenopausal if they have been amenorrhoeic for 12 months or more following cessation of exogenous hormonal treatment and follicle-stimulating hormone levels in the postmenopausal range.
- •Females greater than or equal to 50 years old would be considered postmenopausal if they have been amenorrhoeic for 12 months or more following cessation of all exogenous hormonal treatment.
- •A highly effective method of contraception is defined as one that can achieve a failure rate of less than 1% per year when used consistently and correctly.
- •Females of childbearing potential who are sexually active with a non-sterilised male partner must agree to use one highly effective method of birth control, as defined below, from enrolment throughout the study and until at least 4 weeks after last dose of study intervention.
- •Cessation of contraception after this point should be discussed with a responsible physician.
- •The following are not acceptable methods of contraception: periodic abstinence (calendar, symptothermal, post-ovulation methods), withdrawal (coitus interruptus), spermicides only, and lactational amenorrhoea.
- •Female condom and male condom should not be used together.
- •All WOCBP must have a negative pregnancy test results at Visit 1 and Visit
- •Highly effective birth control methods include: Total sexual abstinence is an acceptable method provided it is the usual lifestyle of the participant (defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments) [periodic abstinence (eg, calendar, ovulation, symptothermal, post-ovulation methods), declaration of abstinence for the duration of exposure to study intervention, and withdrawal are not acceptable methods of contraception], a vasectomised partner, Implanon®, bilateral tubal occlusion, intrauterine device/levonorgestrel intrauterine system, Depo-Proveraâ„¢ injections, oral contraceptive associated with inhibition of ovulation, and Evra Patchâ„¢, Xulaneâ„¢, or NuvaRing® 11 Capable of giving signed informed consent as described in which includes compliance with the requirements and restrictions listed in the ICF and in this protocol 12 Participants are eligible to be considered for the Optional Biomarker and/or Optional Genomics Initiative Research Information only if: a.
- •Provision of signed and dated written Optional Biomarker informed consent prior to optional collection of samples for biomarker research.
- •Provision of signed and dated written Optional Genomics Initiative Research Information and Consent Form prior to collection of samples for optional Genomics Initiative research that supports Genomic Initiative.
排除标准
- •Participants are excluded from the study if any of the following criteria apply: Medical Conditions Cardiac and vascular conditions 1 Systolic BP Less than 100 mmHg, or symptomatic hypotension within the past 24 hours, at randomisation. 2 Systolic BP greater than or equal to 160 mmHg if on treatment with Less than 3 blood pressure lowering medications or greater than or equal to 180 mmHg irrespective of treatments, at enrolment or randomisation. 3 Acute coronary syndrome (unstable angina or myocardial infarction), stroke or transient ischaemic attack within the previous 3 months. 4 Major cardiac surgery, coronary revascularisation or valvular repair or replacement, or implantation of a Cardiac resynchronisation therapy device within 3 months prior to enrolment or planned to undergo any of these operations after randomisation 5 History of the following cardiomyopathies: hypertrophic obstructive, infiltrative (such as but not limited to diagnosed amyloidosis), restrictive, genetic or familial, arrhythmogenic right ventricular cardiomyopathy; Chaga s cardiomyopathy is permitted 6 Active myocarditis or pericardial causes of HF (eg, constriction or tamponade) 7 Complex congenital heart disease or severe uncorrected primary valvular disease 8 Symptomatic bradycardia or second- or third-degree heart block without a pacemaker 9 History of mechanical circulatory support (such as left ventricular assist device), heart transplant or on heart transplant list) 10 Probable alternative or concomitant diagnoses which could account for the participant s HF symptoms and signs (eg, severe anaemia, hypothyroidism, nephrotic syndrome) 11 Primary pulmonary hypertension, chronic pulmonary embolism, severe pulmonary disease including COPD (eg, requiring home oxygen or frequent hospitalisation) or exacerbation of COPD requiring invasive mechanical ventilation assistance within 12 months prior to enrolment) Other diseases 12 Has received kidney replacement therapy in the past 4 weeks, currently requiring kidney replacement or imminent plan to start kidney replacement therapy. 13 Hepatic disease, including active HBV or HCV infection, or other cause of hepatitis, and/or hepatic impairment (Child-Pugh class B-C; or any of AST or ALT greater than 3 × ULN; or TBL greater than 2 × ULN at time of screening at Visit 1). An isolated increase in total bilirubin in patients with known Gilbert s syndrome is not a reason for exclusion, provided that direct bilirubin is normal. 14 Type 1 diabetes mellitus. 15 Addison s disease. 16 Any of the following related to COVID-19 infection: a. Suspected (as judged by PI) or confirmed COVID-19 infection within the last 4 weeks prior to enrolment (Visit 1) or at randomisation (Visit 2). b. Hospitalisation for COVID-19 within the last 12 weeks prior to enrolment (Visit 1). 17 Any condition outside the kidney and CV disease area, such as but not limited to active malignancy requiring treatment, with short life expectancy based on the Investigator s clinical judgement. 18 History of malignancy within the last 5 years, excluding successful treatment of basal or squamous cell skin carcinoma or in situ carcinoma of the cervix. Prior/Concomitant Therapy 19 Treatment with an approved MRA (eg, spironolactone, eplerenone, finerenone) for more than 7 days within the last month prior to randomisation or planned treatment with an MRA. 20 Participants treated with strong or moderate CYP3A4 inhibitor or inducer Prior/Concurrent Clinical Study Experience 21 Participation in another clinical study with a study intervention administered in the last 4 weeks. 22 Participants with a known hypersensitivity to balcinrenone or dapagliflozin or any of the excipients of the product. Other Exclusions 23 Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site). 24 Judgement by the Investigator that the participant should not participate in the study if the participant is unlikely to comply with study procedures, restrictions, and requirements. 25 Previous randomisation in the present study. 26 For females only.
- •currently pregnant (confirmed with positive pregnancy test) or breast-feeding. 1.1 Lifestyle Considerations 1.1.1 Meals and Dietary Restrictions Blood samples will be taken under non-fasting conditions, with exception of samples taken at randomisation (Visit 2), Visit 7, and Visit
- •For samples taken under fasting conditions, participants should fast prior to the collection of blood samples. Fasting is defined as no caloric intake for at least 4 hours prior to the collection of the sample. Participants must avoid grapefruit and grapefruit juice consumption during the study in order to avoid CYP3A4 inhibition. There are no other specific meals and dietary restrictions, however, participants should receive lifestyle advice according to local guidelines as considered relevant for the individual participant based on their medical conditions (eg, T2DM, hypertension, kidney impairment). 1.1.2 Restrictions During the Study Participants will be asked not to take their IMPs at home on the day of study visits (except Visit 3). After completing all pre-dose procedures, provided the participant is permitted to continue in the study following assessments, he/she will take the IMP at the site. Participants should be instructed to contact the site in case of signs of acute illnesses that may increase risk of hyperkalaemia or acute kidney injury (eg, fever, vomiting, diarrhoea, malaise, and/or dehydration). Additional medical check-up and safety samples to be requested at the discretion of the Investigator. Participants with diabetes who experience rapid onset of fatigue, abdominal pain, severe thirst, shortness of breath, and/or vomiting should be instructed to hold IMP until DKA has been ruled out.
结局指标
主要结局
To determine whether balcinrenone/dapagliflozin is superior to dapagliflozin in reducing the risk of CV death, and HF events with and without hospitalisation
时间窗: Enrollment to | - occurrence of Death | - Time when the patient was hospitalized because of HF | - Time patient visit the hospital for an heart failure event
次要结局
- To determine whether balcinrenone/dapagliflozin is superior to dapagliflozin in reducing the rate of total occurrences of CV death, & HF events with & without hospitalisation(Enrollment to)
- To determine whether balcinrenone/dapagliflozin is superior to dapagliflozin in reducing the rate of total HF hospitalisations(Enrollment to)
- To determine whether balcinrenone/dapagliflozin is superior to dapagliflozin in reducing the risk of CV death(Enrollment to)
- To determine whether balcinrenone/dapagliflozin is superior to dapagliflozin in reducing the risk of death from any cause, HF events, & improving patient reported symptoms of HF(Enrollment to)
- To determine whether balcinrenone/dapagliflozin is superior to dapagliflozin in reducing the risk of death from any cause(Enrollment to)
研究者
Dr. Vijay Kumar Chopra
Max Super Speciality Hospital Saket
研究点 (24)
Loading locations...
相似试验
招募中
3 期
Study to compare the Efficacy and Safety of BCD-264 in the treatment of Relapsed and Refractory Multiple MyelomaCTRI/2024/03/063867JSC BIOCAD, Russia452
尚未招募
不适用
A study to find out if adding the medicine Pioglitazone can help control blood sugar better in Indian people with type 2 diabetes who are already taking Glimepiride and MetforminCTRI/2025/08/093017Abbott Healthcare Pvt Ltd60
招募中
不适用
Safety and Effectiveness of Spatial StimelMD (SSMD) in Subjects With Upper Limb Neuromotor ImpairmentsSpinal Cord InjuryStrokeNCT07404761Motion Informatics LTD150
招募中
不适用
To compare the effect of Bala Tail Nasa Pichu And Shigru Tail Nasa Pichu In NasanahaCTRI/2025/09/094754Patanjali Bhartiya Ayurvigyan Evam Anusandhan Sansthan Haridwar60
招募中
2 期
Belvarafenib in Combination With Cobimetinib in Patients With Locally Advanced or Metastatic NRAS-Mutant MelanomaNCT07449754Hanmi Pharmaceutical Company Limited45