A Study to assess the efficacy and safety of Dapagliflozin and Bisoprolol Tablets in heart disease patients.
- Conditions
- Health Condition 1: I502- Systolic (congestive) heart failure
- Registration Number
- CTRI/2023/08/057021
- Lead Sponsor
- Eris Lifesciences Ltd.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 258
1. Male or female patients aged >18 years at the time of screening visit.
2. Patients with diagnosis of heart failure with reduced ejection fraction (HFrEF) with EF = 40% at the time of screening visit.
3. Patients with established documented diagnosis of symptomatic HFrEF (New York Heart Association (NYHA) functional class II-III) at the time of screening visit.
4. Patients should receive a background standard of care for HErEF and be treated according to locally recognized guidelines with both drug and devices, as appropriate. Guideline recommended pharmacological medications should be used at recommended doses unless contraindicated or not tolerated [ diuretic ? and ACE inhibitor ? OR ARB ? and a beta-blocker ? and a mineralocorticoid receptor antagonist (only if considered appropriate by the treating physician)]. Therapy should have been individually optimized and stable for =4 weeks (this does not apply to diuretics).
Note:
? Patients who have not received beta-blockers prior to screening shall be initiated on low dose beta-blocker treatment followed by dose up titration (Bisoprolol 1.25 mg dose once daily for 1 week followed by up-titration to 2.5 mg once daily for 1 week, 5 mg once daily for 2 weeks and 10 mg once daily for 2 weeks) of screening phase (day -42 to day 0).
? The patient’s heart rate should be stable on 10 mg of Bisoprolol.
? Most patients with heart failure require treatment with a diuretic to control sodium and water retention leading to volume overload. It is recognized that diuretic dosing may be titrated to symptoms, signs, weight and other information and may thus vary. Each patient should, however, be treated with a diuretic regimen aimed at achieving optimal fluid/volume status for that individual.
5. Patients with elevated N-terminal pro-B type natriuretic peptide (NT-proBNP) levels at the time of screening visit.
6. Women of childbearing potential (WOCBP) must be using an acceptable method of contraception to avoid pregnancy throughout the study. WOCBP must have a negative urine pregnancy test at screening / baseline visit.
7. Patients with ability to understand and provide written, signed and dated informed consent form, which must have been obtained prior to screening.
8. Patients willing to comply with all the protocol related requirements.
1. Patients with a history of type 1 diabetes mellitus or secondary diabetes mellitus or diabetes insipidus.
2. Patients with a history of metabolic acidosis or diabetic ketoacidosis.
3. Patients with history or present symptoms of bradycardia (pulse rate <60 bpm) and/or hypotension (systolic blood pressure <110 mmHg and diastolic blood pressure <70 mmHg) with or without treatment with beta-blockers at 2 out of 3 measurements either at screening or randomization.
4. Patients with history of bronchial asthma and/or chronic obstructive pulmonary disease (COPD).
5. Patients with a history of genital mycotic infections.
6. Patients with history or present symptoms of recurrent urinary tract infections.
7. Patients with known case of congenital renal glucosuria, history of unstable or rapidly progressing renal disease.
8. Patients with clinically significant impaired hepatic function (SGOT & SGPT more than 3X the UNL and/or Total bilirubin more than 2X the UNL) at screening.
9. Patients with clinically significant renal disorders:
? Estimated glomerular filtration rate: <30 mL/min/1.73 m2.
? Serum creatinine and blood urea nitrogen (BUN) values =1.5 times the upper limit of normal.
10. Patients with current acute decompensated HF or hospitalization due to decompensated HF <4 weeks prior to enrolment.
11. Patients with MI, unstable angina, stroke or transient ischemic attack (TIA) within 12 weeks prior to randomization.
12. Patients with Coronary revascularization (percutaneous coronary intervention [PCI] or coronary artery bypass grafting [CABG]) or valvular repair/replacement within 12 weeks prior to randomization or planned to undergo any of these operations after randomization.
13. Patients with implantation of a cardiac CRT within 12 weeks prior to enrolment or intent to implant a CRT device.
14. Patients with previous cardiac transplantation or implantation of a ventricular assistance device (VAD) or similar device, or implantation expected after randomization.
15. Patients with HF due to restrictive cardiomyopathy, active myocarditis, constrictive pericarditis, hypertrophic (obstructive) cardiomyopathy or uncorrected primary valvular disease.
16. Patients with symptomatic bradycardia or second or third degree heart block without a pacemaker.
17. Patients with any condition outside the CV and renal disease area, such as but not limited to malignancy, with a life expectancy of less than 2 years based on investigator´s clinical judgement.
18. Patients with active malignancy requiring treatment at the time of screening visit.
19. Patients with intolerance, contraindication or potential allergy/hypersensitivity to any of the ingredients of study medication or beta-blockers or SGLT2 inhibitors.
20. Female patients who are pregnant or breast-feeding or expecting to conceive within the projected duration of the study.
21. Female patients who are of childbearing potential and who are neither surgically sterilized nor willing to use reliable contraceptive methods (like hormonal, barrier methods or intrauterine device).
22. Patients receiving treatment with SGLT2 inhibitors within 8 weeks prior to enrolment.
23. Patients with EF <25% as per Simpson’s method on 2D Echo.
24. Patients with a history of substance abuse or dependence that in the opinion of the Investigat
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Mean improvement of ejection fraction (EF) from baseline to end of the study visit.Timepoint: At Screening / Baseline Visit, <br/ ><br>Day 90 & Day 180.
- Secondary Outcome Measures
Name Time Method Adverse events & serious adverse events reportedduring the study.Timepoint: Throughout the study.;Changes in clinical laboratory parameters from baseline to end of the study visit (180 days).Timepoint: At Screening / Baseline Visit, <br/ ><br>Day 90 & Day 180.;Mean change in plasma NT-pro BNP levels from baseline to end of the study visit.Timepoint: At Screening / Baseline Visit, <br/ ><br>Day 90 & Day 180.;Mean changes in vital parameters (blood pressure & heart rate) from baseline to end of the study visit.Timepoint: At Screening / Baseline Visit, <br/ ><br>Day 14, Day 45, Day 90, Day 135 & Day 180.;Mean improvement in NYHA functional class from baseline to end of the study visit.Timepoint: At Screening / Baseline Visit, <br/ ><br>Day 90 & Day 180.