CTRI/2024/03/064908 [Registered on: 28/03/2024] Trial Registered Prospectively
Last Modified On:
03/04/2025
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 study to assess the efficacy and safety of Dapagliflozin and Sacubitril/Valsartan Tablets in heart disease patients.
Scientific Title of Study
A Phase III, Randomized, Open Label, Active-Controlled, Prospective, Parallel Group, Comparative, Multicentric Clinical Study to Evaluate the Efficacy, Safety and Tolerability of Fixed Dose Combination of Dapagliflozin and Sacubitril/Valsartan Tablets Versus Concomitant Administration of Dapagliflozin and Sacubitril/Valsartan Tablets in Patients with Heart Failure with Reduced Ejection Fraction (HFrEF).
Trial Acronym
NIL
Secondary IDs if Any
Secondary ID
Identifier
CT/2023/03, Version No.: 00, Dated Jan 16, 2023
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Dr Rajasekhara Reddy Tamma
Designation
Managing Director
Affiliation
CLINWAVE RESEARCH PRIVATE LIMITED
Address
Clinwave Research Pvt. Ltd.,
LIG: B/466, H. No.: 1-16-10/466,
Dr. A.S. Rao Nagar, Kapra,
Medchal-Malkajgiri (Dist.).
Medchal TELANGANA 500062 India
Phone
7989233379
Fax
Email
dr.sekhar@clinwave.co.in
Details of Contact Person Scientific Query
Name
Dr Rajasekhara Reddy Tamma
Designation
Managing Director
Affiliation
CLINWAVE RESEARCH PRIVATE LIMITED
Address
Clinwave Research Pvt. Ltd.,
LIG: B/466, H. No.: 1-16-10/466,
Dr. A.S. Rao Nagar, Kapra,
Medchal-Malkajgiri (Dist.).
Department of Cardiology,
Medical College and Hospital, Kolkata,
MCH Building, 4th Floor,
88 College Street,
Kolkata-700073. Kolkata WEST BENGAL
9433113112
doc.kuntal.227@gmail.com
Dr Swapan Kumar Halder
Nil Ratan Sarkar Medical College and Hospital
Nil Ratan Sarkar Medical College and Hospital,
Kolkata, 138, Acharya Jagadish Chandra Bose Road, Sealdah, Raja Bazar,
Kolkata-700014. Kolkata WEST BENGAL
9433428061
drskh@rediffmail.com
Dr Krishna Mala Konda Reddy P
Osmania Medical College & General Hospital
Department of Cardiology,
Osmania Medical College & General Hospital,
Afzalgunj, Hyderabad. Hyderabad TELANGANA
9848015098
drkmkreddyp@yahoo.com
Dr Sandarbh Patel
Sheth Vadilal Sarabhai General Hospital
Sheth Vadilal Sarabhai General Hospital,
Nr. Ellisbridge, Paldi,
Ahmedabad-380006. Ahmadabad GUJARAT
9909031385
drsandarbh.cardio@gmail.com
Dr Satish Suryavanshi
SMC Heart Institute and IVF Research Centre
Clinical Research Room, Infront of BSNL Office, Vidhan Sabha Road, Khamardih, Raipur-492007.
Raipur CHHATTISGARH
9826334404
drsatish_suryavanshi@yahoo.co.in
Dr Dipak Ranjan Das
Srirama Chandra Bhanja Medical College and Hospital
Department of Cardiology, Srirama Chandra Bhanja Medical College and Hospital,
Cuttack-753007. Cuttack ORISSA
9437165904
maildrdipak@gmail.com
Dr Abhishek Sachdeva
Swaroop Rani Motilal Nehru Medical College
Department of Cardiology,
Swaroop Rani Motilal Nehru Medical College,
Prayagraj-211001. Allahabad UTTAR PRADESH
Concomitant Administration of Dapagliflozin Tablets 5 mg and Sacubitril/Valsartan Tablets 97/103 mg
Patients will be advised to take one tablet of Dapagliflozin Tablets 5 mg and one tablet of Sacubitril/Valsartan Tablets 97/103 mg twice a day orally, swallowed with water in the morning and evening around same time every day for 24 weeks.
Intervention
FDC of Dapagliflozin 5 mg + Sacubitril/Valsartan 97/103 mg Tablets
Patients will be advised to take one tablet twice a day orally, swallowed with water in the morning and evening around same time every day for 24 weeks.
Inclusion Criteria
Age From
18.00 Year(s)
Age To
80.00 Year(s)
Gender
Both
Details
1.Male or female patients aged Greater than 18 years diagnosed with heart failure with reduced ejection fraction (HFrEF) with EF less than or equal to 40%.
2.Patients with established documented diagnosis of symptomatic HFrEF (New York Heart Association (NYHA) functional class II-III).
3.Patients should be on maximum dose of Sacubitril/Valsartan Tablets 97/103 mg twice daily.
4.Patients should receive background standard of care for HFrEF and be treated according to locally recognized guidelines with both drugs and devices, as appropriate. Guideline-recommended medications should be used at recommended doses unless contraindicated or not tolerated.
5.Patients with elevated N-terminal pro-B type natriuretic peptide (NT-proBNP) levels at the time of screening visit.
6.Patients with estimated glomerular filtration rate (eGFR) ≥30 ml/min/1.73 m2 at screening visit.
7.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.
8.Patient with ability to understand and provide written, signed and dated informed consent form, which must have been obtained prior to screening.
9.Patients willing to comply with all the protocol related requirements.
ExclusionCriteria
Details
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 symptoms of hypotension or systolic blood pressure Less than 95 mmHg, 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 hyperkalemia (serum potassium level of more than 5.5 mEq per litre).
7.Patients with type 2 diabetes mellitus whose diabetes has not been stable and controlled for the previous three months and with HbA1c value Greater than or Equal to 8%.
8.Patients receiving treatment for type 2 diabetes mellitus with SGLT2 inhibitors within 8 weeks prior to screening visit.
9.Patients with history of angioedema and multi-organ dysfunction.
10.Patients with a history of genital mycotic infections.
11.Patients with intolerance, contraindication or potential allergy/hypersensitivity to SGLT-2 inhibitors.
12.Female patients who are pregnant or breast-feeding or expecting to conceive within the projected duration of the study.
13.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).
14.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.
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/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 concurrent participation in another clinical trial or any investigational therapy within 90 days prior to signing informed consent.
25.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.
26.Patients currently taking any of the prohibited medications(s) and inability/unwillingness to discontinue them for the entire study period.
27.Patients with suspected inability or unwillingness to comply with the study procedures.
28.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
An Open list of random numbers
Blinding/Masking
Open Label
Primary Outcome
Outcome
TimePoints
Mean improvement of ejection fraction (EF) from baseline to end of the study visit (Week 24).
Visit 1 - Screening or Baseline visit (Day -7),
Visit 5 - Follow up visit / Week 12 (Day 84±3) and
Visit 7 - End of the study visit / 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).
Visit 1 - Screening or Baseline visit (Day -7)
Visit 5 - Follow up visit / Week 12 (Day 84±3)
Visit 7 - End of the study visit / Week 24 (Day 168±3)
Mean change in plasma NT-pro BNP levels from baseline to end of the study visit (Week 24).
Visit 1 - Screening or Baseline visit (Day -7)
Visit 5 - Follow up visit / Week 12 (Day 84±3)
Visit 7 - End of the study visit / 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).
Visit 1 - Screening or Baseline visit (Day -7)
Visit 2 - Randomization visit (Day 1)
Visit 3 - Follow up visit / Week 2 (Day 14±3)
Visit 4 - Follow up visit / Week 6 (Day 42±3)
Visit 5 - Follow up visit / Week 12 (Day 84±3)
Visit 6 - Follow up visit / Week 18 (Day 126±3)
Visit 7 - End of the study visit / Week 24 (Day 168±3)
Mean change in the potassium levels from baseline to end of the study visit (Week 24)
Visit 1 - Screening or Baseline visit (Day -7)
Visit 4 - Follow up visit / Week 6 (Day 42±3)
Visit 5 - Follow up visit / Week 12 (Day 84±3)
Visit 6 - Follow up visit / Week 18 (Day 126±3)
Visit 7 - End of the study visit / 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 & serious adverse events during the Study.
Throughout the Study
Target Sample Size
Total Sample Size="230" Sample Size from India="230" Final Enrollment numbers achieved (Total)= "232" Final Enrollment numbers achieved (India)="232"
Phase of Trial
Phase 3
Date of First Enrollment (India)
08/04/2024
Date of Study Completion (India)
20/03/2025
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)?
Response - NO
Brief Summary
This trial is a Phase III, Randomized, Open Label, Active-Controlled, Prospective, Parallel Group, Comparative, Multicentric Clinical Study to Evaluate the Efficacy, Safety and Tolerability of Fixed Dose Combination of Dapagliflozin and Sacubitril/Valsartan Tablets Versus Concomitant Administration of Dapagliflozin and Sacubitril/Valsartan Tablets in Patients with Heart Failure with Reduced Ejection Fraction (HFrEF).
Patients who are willing and able to participate in the study will sign and date the Informed Consent Form on the day of screening / baseline 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 > 18 years with heart failure with reduced ejection fraction (HFrEF) with EF ≤ 40%, established documented diagnosis of symptomatic HFrEF (New York Heart Association (NYHA) functional class II-III), on maximum dose of Sacubitril/Valsartan Tablets 97/103 mg twice daily, with elevated N-terminal pro b-type natriuretic peptide (NT-proBNP) levels at screening visit 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 two arms i.e., Arm A or Arm B consisting of FDC of Dapagliflozin 5 mg + Sacubitril/Valsartan 97/103 mg Tablets or Concomitant Administration of Dapagliflozin Tablets 5 mg and Sacubitril/Valsartan Tablets 97/103 mg (Arm B).