CTRI/2025/02/080247 [Registered on: 10/02/2025] Trial Registered Prospectively
Last Modified On:
18/02/2026
Post Graduate Thesis
No
Type of Trial
Interventional
Type of Study
Drug
Study Design
Randomized, Parallel Group, Active Controlled Trial
Public Title of Study
A clinical study to assess the efficacy and safety of Eplerenone and Torsemide Tablets in heart patients.
Scientific Title of Study
A Phase III, Prospective, Randomized, Double Blind, Active Controlled, Comparative, Parallel Group, Multicenter Clinical Study to Evaluate the Efficacy, Safety and Tolerability of Fixed Dose Combination of Eplerenone plus Torsemide Tablets Versus Fixed Dose Combination of Spironolactone plus Torsemide Tablets in Patients with Congestive Heart Failure.
Trial Acronym
NIL
Secondary IDs if Any
Secondary ID
Identifier
CT/2024/20, Version No.: 01 and Dated Sep 28, 2024
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Institutional Ethics Committee, Motilal Nehru Medical College
Approved
Institutional Ethics Committee, Osmania Medical College
Approved
Institutional Ethics Committee, Visakha Institute of Medical Sciences (VIMS)
Approved
Latha Super Specialities Hospital Ethics Committee, Latha Super Specialities Hospital
Approved
Prakash Medical College Institutional Ethics Committee, Prakash Institute of Medical Sciences & Research (PIMS&R)
Approved
Rajarshee Chhatrapati Shahu Maharaj Govt. Medical College Institutional Ethics Committee 2 (RCSMGMCIEC2), Rajarshee Chhatrapati Shahu Maharaj Govt. Medical College and Chhatrapati Pramila Raje General Hospital
Approved
Shree Institutional Ethics Committee, Dhadiwal Hospital In Coalition with Shreeji Health Care (Swastik Dhadiwal Hospital)
Approved
SMC Heart Institute Institutional Ethics Committee, SMC Heart Institute and IVF Research Centre
Approved
Supe Hospital Ethics Committee, Supe Heart and Diabetes Hospital and Research Centre
Patients will be advised to take one tablet once daily orally, swallowed with water around same time every day for 24 weeks.
Intervention
FDC of Eplerenone 25 mg + Torsemide 20 mg Tablets
Patients will be advised to take one tablet once daily orally, swallowed with water around same time every day for 24 weeks.
Comparator Agent
FDC of Spironolactone 25 mg + Torsemide 20 mg Tablets
Patients will be advised to take one tablet once daily orally, swallowed with water around same time every day for 24 weeks.
Inclusion Criteria
Age From
19.00 Year(s)
Age To
80.00 Year(s)
Gender
Both
Details
1. Male and female patients aged more than 18 years with documented diagnosis of congestive heart failure at the time of screening visit.
2. Patients with New York Heart Association (NYHA) functional class II or III symptoms at the time of screening visit.
3. Patients with ejection fraction (EF) less than 40% at the time of screening visit.
4. Patients with a plasma level of NT-pro BNP (N-terminal pro-B type natriuretic peptide) should be more than 120 pg/mL at the time of screening visit.
5. Patients should receive a background standard of care for congestive heart failure and be treated according to locally recognized guidelines. Guideline recommended pharmacological medications should be used at recommended doses unless contraindicated or not tolerated (“ACE inhibitor†OR “ARB†and a “beta-blockerâ€). Therapy should have been individually optimized and stable for more than or equal to 4 weeks.
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. Patient with ability to understand and provide written informed consent form, which must have been obtained prior to screening.
8. Patients are willing to comply with the protocol requirements throughout the study.
ExclusionCriteria
Details
1. Patients with known hypersensitivity to study medication or related class of drugs.
2. Patients with history or present symptoms of bradycardia (pulse rate less than 60 bpm) and or hypotension (systolic blood pressure less than 95 mmHg and diastolic blood pressure less than 70 mmHg) with or without treatment with beta-blockers at 2 out of 3 measurements either at screening or randomization.
3. Patients with symptoms recent worsening heart failure or other cardiovascular events or procedures (or planned procedures).
4. Patients with hypoxia, a room air saturation of less than 95%.
5. Patients with ongoing myocardial ischemia requiring revascularization.
6. Patients with present or history of hypokalemia (serum potassium level of less than 3.5 mEq per litre) or hyperkalemia (serum potassium level of more than 5.5 mEq per litre) at screening visit.
7. Patients with hyponatremia as per blood biochemistry results at screening visit.
8. Patients with a history of type 1 diabetes mellitus or secondary diabetes mellitus or diabetes insipidus.
9. Patients with type 2 diabetes mellitus whose diabetes has not been stable and controlled for the previous three months and with HbA1c value more than or equal to 8%.
10. Patients with history of angioedema and multi-organ dysfunction.
11. Female patients who are pregnant or breast-feeding or expecting to conceive within the projected duration of the study.
12. 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).
13. 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.
14. Patients with clinically significant renal disorders:
Estimated glomerular filtration rate: less than 30 mL per min per 1.73 m2.
Serum creatinine and blood urea nitrogen (BUN) values more than or equal to 1.5 times the upper limit of normal.
15. Patients with current acute decompensated HF or hospitalization due to decompensated HF less than 4 weeks prior to enrolment.
16. Patients with MI, unstable angina, stroke or transient ischemic attack (TIA) within 12 weeks prior to randomization.
17. Patients with Coronary revascularization (percutaneous coronary intervention [PCI] or coronary artery bypass grafting [CABG]) or valvular repair or replacement within 12 weeks prior to randomization or planned to undergo any of these operations after randomization.
18. Patients with implantation of a cardiac CRT within 12 weeks prior to enrolment or intent to implant a CRT device.
19. Patients with previous cardiac transplantation or implantation of a ventricular assistance device (VAD) or similar device, or implantation expected after randomization.
20. Patients with HF due to restrictive cardiomyopathy, active myocarditis, constrictive pericarditis, hypertrophic (obstructive) cardiomyopathy or uncorrected primary valvular disease.
21. Patients with symptomatic bradycardia or second or third degree heart block without a pacemaker.
22. 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.
23. Patients with an active or history of malignancy requiring treatment.
24. Patients with EF less than 25% as per Simpson’s method on 2D Echo.
25. Patients with known case of infection with hepatitis B, hepatitis C or HIV.
26. Patients with concurrent participation in another clinical trial or any investigational therapy within 90 days prior to signing informed consent.
27. Patients with a history of substance abuse or dependence that in the opinion of the Investigator is considered to interfere with the patient’s participation in the study.
28. Patients currently taking any of the prohibited medications(s) and inability or unwillingness to discontinue them for the entire study period.
29. Patients with suspected inability or unwillingness to comply with the study procedures.
30. Patient with any condition which, in the judgment of the Investigator, may render the patient unable to complete the study or which may pose a significant risk to the patient.
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
Pre-numbered or coded identical Containers
Blinding/Masking
Participant and Investigator Blinded
Primary Outcome
Outcome
TimePoints
At least one class improvement in NYHA functional class from baseline to end of the study visit (Week 24).
At Visit 1 - Screening or Baseline visit,
Visit 3 - Follow up visit or Week 2 (Day 14±3),
Visit 4 - Follow up visit or Week 6 (Day 42±3),
Visit 5 - Follow up visit or Week 12 (Day 84±3),
Visit 6 - Follow up visit or Week 18 (Day 126±3) and
Visit 7 - End of the study visit or Week 24 (Day 168±3).
Secondary Outcome
Outcome
TimePoints
Mean improvement in NYHA functional class from baseline to end of the study visit (Week 24).
At Visit 1 - Screening or Baseline visit,
Visit 3 - Follow up visit or Week 2 (Day 14±3),
Visit 4 - Follow up visit or Week 6 (Day 42±3),
Visit 5 - Follow up visit or Week 12 (Day 84±3),
Visit 6 - Follow up visit or Week 18 (Day 126±3) and
Visit 7 - End of the study visit or Week 24 (Day 168±3).
Mean improvement of ejection fraction (EF) from baseline to end of the study visit (Week 24).
At Visit 1 - Screening or Baseline visit,
Visit 5 - Follow up visit or Week 12 (Day 84±3) and
Visit 7 - End of the study visit or Week 24 (Day 168±3).
Mean change in the potassium levels from baseline to end of the study visit (Week 24).
At Visit 1 - Screening or Baseline visit,
Visit 4 - Follow up visit or Week 6 (Day 42±3),
Visit 5 - Follow up visit or Week 12 (Day 84±3),
Visit 6 - Follow up visit or Week 18 (Day 126±3) and
Visit 7 - End of the study visit or Week 24 (Day 168±3).
Mean change in plasma NT-pro BNP levels from baseline to end of the study visit (Week 24).
At Visit 1 - Screening or Baseline visit,
Visit 5 - Follow up visit or Week 12 (Day 84±3) and
Visit 7 - End of the study visit or Week 24 (Day 168±3).
Mean changes in vital parameters (blood pressure and heart rate) from baseline to end of the study visit (Week 24).
At Visit 1 - Screening or Baseline visit,
Visit 2 - Randomization visit (Day 1),
Visit 3 - Follow up visit or Week 2 (Day 14±3),
Visit 4 - Follow up visit or Week 6 (Day 42±3),
Visit 5 - Follow up visit or Week 12 (Day 84±3),
Visit 6 - Follow up visit or Week 18 (Day 126±3) and
Visit 7 - End of the study visit or Week 24 (Day 168±3).
Worsening heart failure (hospitalization or an urgent visit resulting in intravenous therapy for heart failure) from baseline to end of the study visit (Week 24).
Throughout the study
Adverse events and Serious adverse events reported during the study.
Throughout the study
Changes in clinical laboratory parameters from baseline to end of the study visit (Week 24).
At Visit 1 - Screening or Baseline visit,
Visit 3 - Follow up visit or Week 2 (Day 14±3),
Visit 4 - Follow up visit or Week 6 (Day 42±3),
Visit 5 - Follow up visit or Week 12 (Day 84±3),
Visit 6 - Follow up visit or Week 18 (Day 126±3) and
Visit 7 - End of the study visit or Week 24 (Day 168±3).
Target Sample Size
Total Sample Size="288" Sample Size from India="288" Final Enrollment numbers achieved (Total)= "288" Final Enrollment numbers achieved (India)="288"
Phase of Trial
Phase 3
Date of First Enrollment (India)
10/02/2025
Date of Study Completion (India)
07/01/2026
Date of First Enrollment (Global)
Date Missing
Date of Study Completion (Global)
Date Missing
Estimated Duration of Trial
Years="1" Months="0" Days="0"
Recruitment Status of Trial (Global)
Not Applicable
Recruitment Status of Trial (India)
Completed
Publication Details
N/A
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Patients
who are willing and able to participate in the study will sign and date the
Informed Consent Form on the day of screening visit (Visit 1). During this
screening period, patients who are willing to give consent will be evaluated
for all the eligibility criteria. Eligible patients (male or female) aged
between 18 years and above meeting all the inclusion criteria and none of the
exclusion criteria prior to screening will be considered for the study.
After confirming the inclusion/exclusion criteria the
subject will be randomized and provided with study medication at randomization
visit. Subjects will be provided with patient diary at randomization visit,
which need to be brought along with in each subsequent visit till the last
visit. Follow up visits will be done on week 2/day 14(±3), week 6/day 42(±3), week
12/day 84(±3), week 18/day 126(±3) and week 24/day 168(±3) (final visit) of
treatment to assess efficacy, safety and tolerability.
Patients
will be assigned to either of the three arms i.e., Arm A or Arm B or Arm C consisting
of FDC of Eplerenone 25 mg + Torsemide 10 mg Tablets or FDC of Eplerenone 25 mg
+ Torsemide 20 mg Tablets or FDC of Spironolactone 25 mg + Torsemide 20 mg
Tablets. Patients will be advised to take one tablet once daily orally,
swallowed with water around same time every day for 24 weeks.