CTRI/2024/12/077518 [Registered on: 02/12/2024] Trial Registered Prospectively
Last Modified On:
14/07/2026
Post Graduate Thesis
No
Type of Trial
Interventional
Type of Study
Drug
Study Design
Randomized, Parallel Group Trial
Public Title of Study
A research study to evaluate the effect of balcinrenone/dapagliflozin in patients with heart failure and impaired kidney function
Scientific Title of Study
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)
Trial Acronym
BalanceD-HF
Secondary IDs if Any
Secondary ID
Identifier
D6402C00012 Version number 2.0 dated 11 Jan 2024
Protocol Number
Local CSP Addendum IND-1: Version 1.0, dated 06 MAR 2024
Protocol Number
NCT06307652
ClinicalTrials.gov
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Dr. Vijay Kumar Chopra
Designation
Senior Director, Department of Cardiology
Affiliation
Max Super Speciality Hospital Saket
Address
Max Super Speciality Hospital Saket (East Block) (A Unit of Devki Devi Foundation), 2, Press Enclave Road, Saket
AstraZeneca Pharma India Ltd,
Block N1, 12th Floor, Manyata Embassy Business Park,
Rachenahalli, Outer Ring Road, Bangalore
KARNATAKA 560045 India
Phone
9535104975
Fax
Email
tapankumar.shah@astrazeneca.com
Source of Monetary or Material Support
AstraZeneca AB, 151 85 Södertälje, Sweden
AstraZeneca K.K., 3-1, Ofuka-cho, Kita-ku, Osaka 530-0011, Japan
Primary Sponsor
Name
AstraZeneca AB
Address
151 85 Södertälje, Sweden
Type of Sponsor
Pharmaceutical industry-Global
Details of Secondary Sponsor
Name
Address
AstraZeneca Pharma India Ltd
Block N1, 12th Floor, Manyata Embassy Business Park,
Rachenahalli, Outer Ring Road, Bangalore - 560045,
Karnataka, India
Countries of Recruitment
Argentina Australia Austria Brazil Bulgaria Canada Chile China Colombia Czech Republic Finland France Germany Greece Hungary India Israel Italy Japan Malaysia Mexico Netherlands Peru Philippines Poland Republic of Korea Romania Saudi Arabia Slovakia South Africa Spain Sweden Taiwan Thailand Turkey United Kingdom United States of America Viet Nam
Senior Interventional Cardiologist, Department of Cardiology, 6-3-248/2, Road No.1, Banjara Hills, PIN- 500034 Hyderabad TELANGANA
9848047521
dr.kaparthi@gmail.com
Dr Gurpreet Singh Wander
Dayanand Medical College and Hospital
Dayanand Medical College and Hospital, Tagore Nagar, Civil Lines, PIN -141001 Ludhiana PUNJAB
9815545316
drgswander@yahoo.com
Dr Rajeev Garg
Gleneagles AWARE Hospital
Senior Interventional Cardiologist, Department of Cardiology, 08-16-01, Near Sagar X roads, Saroornagar, L.B Nagar, PIN- 5600035 Hyderabad TELANGANA
9848028238
drsrajeevsangeeta@yahoo.co.in
Dr Vimal Mehta
Govind Ballabh Pant Institute of Postgraduate Medical Education and Research
Director-Professor, Department of Cardiology,Govind Ballabh Pant Institute of Postgraduate Medical Education and Research, First Floor, Academic Block, Department of Cardiology, Jawahar Lal Nehru Marg, PIN - 110002 New Delhi DELHI
9718599105
drvimalmehta@yahoo.co.in
Dr Barama Srihari
Govt. Siddhartha Medical College
Assistant Professor, Department of Cardiology, Ring road, Gunadala, Vijayawada, PIN - 520008 Krishna ANDHRA PRADESH
7799851491
srihari7399@gmail.com
Dr Santosh Kumar Sinha
GSVM Medical College, LPS Institute of Cardiology
Associate Professor, Department of Cardiology, GSVM Medical College, LPS Institute of Cardiology & Cardiac Surgery, Swaroop Nagar, PIN- 208002 Kanpur Nagar UTTAR PRADESH
9670220088
fionasan@rediffmail.com
Dr Sankar Chandra Mondal
Institute of Post-Graduate Medical Education & Research
Professor, Department of Cardiology, Institute of Post-Graduate Medical Education & Research (IPGME&R) and Seth Sukhlal Karnani Memorial (SSKM) Hospital, 244, Acharya J. C. Bose Road, Bhowanipore, PIN-700020 Kolkata WEST BENGAL
9433009582
drscmandal5@gmail.com
Dr Nitthiyan
K. G. Hospital, and Post Graduate Medical Institute and Research Centre
K. G. Hospital, and Post Graduate Medical Institute and Research Centre, No 5, Government Arts College Road, Coimbatore, Tamilnadu- 641018 India Coimbatore TAMIL NADU
9159940950
nitthi94@gmail.com
Dr Tom Devasia
Kasturba Medical College and Hospital,
Professor and Unit Head, Department of Cardiology, MAHE, Tiger Circle Road, Madhav Nagar, Eshwar Nagar, PIN-576104 Dakshina Kannada KARNATAKA
8310996246
tom.devasia@manipal.edu
Dr Prasad Murigendrappa Renuka
KLES Dr Prabhakar Kore Hospital & Medical Research Centre
Consultant Interventional Cardiologist, Department of Cardiology, Nehru Nagar, PIN-590010 Belgaum KARNATAKA
9243245777
drprasadmr@gmail.com
Dr Vijay Kumar Chopra
Max Super Speciality Hospital Saket
Senior Director, Department of Cardiology, (East Block) (A Unit of Devki Devi Foundation), 2, Press Enclave Road, Saket, PIN - 110017 New Delhi DELHI
9650896800
vijay.chopra@maxhealthcare.com
Dr Srikanth K V
Narayana Institute of Cardiac Sciences -Unit of Narayana Health
Senior Consultant Cardiologist, Department of Cardiology, Narayana Hrudayalaya Limited, #258/A, Bommasandra Industrial Area, Anekal Taluk, PIN- 560099 Bangalore KARNATAKA
9342658468
srikanth.kv.dr01@narayanahealth.org
Dr Swapan Kumar Halder
Nil Ratan Sircar (NRS) Medical College and Hospital
Associate Professor, Department of Cardiology, 138, Acharya Jagadish Chandra Bose Road, Sealdah, PIN- 700014 Kolkata WEST BENGAL
8777450953
drskh@rediffmail.com
Dr Tanuj Bhatia
Shri Guru Ram Rai Institute of Medical and Health Sciences and Shri Mahant Inderesh Hospital
Dept. of Cardiology,
Patel Nagar, Dehradun, PIN- 248001, Uttarakhand India Dehradun UTTARANCHAL
9936618283
tanujbhatia21@rediffmail.com
Dr Gaurav Mohan
Sri Guru Ram Das Institute of Medical Sciences and Research, Amritsar
VPO Vallah, Mehta Road, Amritsar, PIN, 143501, India Amritsar PUNJAB
Balcinrenone/Dapagliflozin and matching
placebo for Dapagliflozin 10 mg; Dose: 15 mg/10 mg; Route: Oral; Frequency: once daily
Intervention
Balcinrenone/ Dapagliflozin
Balcinrenone/Dapagliflozin and matching
placebo for Dapagliflozin 10 mg; Dose: 40 mg/10 mg; Route: Oral; Frequency: once daily
Comparator Agent
dapagliflozin
Dapagliflozin 10 mg and matching placebo for balcinrenone/ dapagliflozin; Dose: 10 mg; Route: Oral; Frequency: once daily
Inclusion Criteria
Age From
18.00 Year(s)
Age To
99.00 Year(s)
Gender
Both
Details
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.
a. 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. 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)
7 An eGFR greater than or equal to 20 to Less than 60 mL/min/1.73 m2, from Visit 1.
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.
a. 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.
a. 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.
c. 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.
d. Female participants of childbearing potential must use one highly effective form of birth control. 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.
e. 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.
f. All WOCBP must have a negative pregnancy test results at Visit 1 and Visit 2.
g. 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-Provera™ injections, oral contraceptive associated with inhibition of ovulation, and Evra Patch™, Xulane™, 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.
b. 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
ExclusionCriteria
Details
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 9. 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.
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
Centralized
Blinding/Masking
Participant and Investigator Blinded
Primary Outcome
Outcome
TimePoints
To determine whether balcinrenone/dapagliflozin is superior to dapagliflozin in reducing the risk of CV death, and HF events with and without hospitalisation
Enrollment to
- occurrence of Death
- Time when the patient was hospitalized because of HF
- Time patient visit the hospital for an heart failure event
Secondary Outcome
Outcome
TimePoints
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
- Occurrence of Death
- Total number of hospitalization due to Hearth Failure
- Total number of visits to hospital due to heart failure.
To determine whether balcinrenone/dapagliflozin is superior to dapagliflozin in reducing the rate of total HF hospitalisations
Enrollment to
- Occurrence of Death
- Total number of hospitalization due to Hearth Failure
To determine whether balcinrenone/dapagliflozin is superior to dapagliflozin in reducing the risk of CV death
Enrollment to
- Occurrence of Death
- Total number of hospitalization due to Hearth Failure
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
- Occurrence of Death
- Total number of hospitalization due to Hearth Failure
To determine whether balcinrenone/dapagliflozin is superior to dapagliflozin in reducing the risk of death from any cause
Enrollment to
- Occurrence of Death
- Total number of hospitalization due to Hearth Failure
Target Sample Size
Total Sample Size="4800" Sample Size from India="220" Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials" Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials"
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
Brief Summary
Thisisthefirstlong-termstudyevaluatingtheefficacyandsafetyofthecombinationof balcinrenone and dapagliflozin in patients with HF and
impaired kidney function.
Theprimaryhypothesisofthe studyisthatbalcinrenone/dapagliflozin(either15 mg/10 mgor 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 kidneyfunction.Theselectionandadjudicationoftheprimaryandsecondaryendpointsare 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),whichassessesdifferencesinoutcomes betweentreatmentgroupsovertheperiodfrom 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.
Thestudywillevaluategeneralsafetyand tolerabilityofbalcinrenone/dapagliflozincompared 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).