A Study to assess the efficacy and safety of Dapagliflozin and Metoprolol Tablets in heart disease patients.

Phase 3

Completed

• Conditions: Health Condition 1: I502- Systolic (congestive) heart failure

• Registration Number: CTRI/2023/11/060062
• Lead Sponsor: Exemed Pharmaceuticals

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Completion: 2024-07-24
• Last Update Posted: 19 August 2024

Recruitment & Eligibility

• Status: Completed
• Sex: Not specified
• Target Recruitment: 267

Inclusion Criteria

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 cardiologist)]. 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 (Metoprolol Succinate Extended Release Tablets 25 mg once daily for first 2 weeks followed by up-titration to Metoprolol Succinate Extended Release Tablets 50 mg once daily for next 2 weeks) in the screening phase (day -28 to day 0).

? The patient’s heart rate should be stable on Metoprolol Succinate Extended Release Tablets 50 mg.

? 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.

Exclusion Criteria

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 <95 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 symptoms recent worsening heart failure or other cardiovascular events or procedures (or planned procedures).

5. Patients with hypoxia, a room air saturation of less than 95%.

6. Patients with ongoing myocardial ischemia requiring revascularization.

7. Patients with present or history of hyperkalemia (serum potassium level of more than 5.5 mEq per litre).

8. Patients with type 2 diabetes mellitus whose diabetes has not been stable and controlled for the previous three months and with HbA1c value = 8%.

9. Patients receiving treatment for type 2 diabetes mellitus with SGLT2 inhibitors within 8 weeks prior to screening visit.

10. Patients with history of angioedema and multi-organ dysfunction.

11. Patients with history of bronchial asthma and/or chronic obstructive pulmonary disease (COPD).

12. Patients with a history of genital mycotic infections.

13. Patients with history or present symptoms of recurrent urinary tract infections.

14. Patients with known case of congenital renal glucosuria, history of unstable or rapidly progressing renal disease.

15. Patients with intolerance, contraindication or potential allergy/hypersensitivity to SGLT-2 inhibitors.

16. Female patients who are pregnant or breast-feeding or expecting to conceive within the projected duration of the study.

17. 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).

18. 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.

19. 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.

20. Patients with current acute decompensated HF or hospitalization due to decompensated HF <4 weeks prior to enrolment.

21. Patients with MI, unstable angina, stroke or transient ischemic attack (TIA) within 12 weeks prior to randomization.

22. 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.

23. Patients with implantation of a cardiac CRT within 12 weeks prior to enrolment or intent to implant a CRT device.

24. Patients with previous cardiac transplantation or implantation of a ventricular assistance device (VAD) or similar device, or implantation expected after randomization.

25. Patients with HF due to restrictive cardiomyopathy, active myocarditis, constrictive pericarditis, hypertrophic (obstructive) cardiomyopathy or uncorrecte

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 (Week 24).Timepoint: At Screening / Baseline Visit (Visit 1), <br/ ><br>Visit 5 - Follow up visit / Week 12 (Day 84±3) and <br/ ><br>Visit 7 - End of the study visit / Week 24 (Day 168±3).