CTRI/2020/11/029176 [Registered on: 17/11/2020] Trial Registered Prospectively
Last Modified On:
28/01/2022
Post Graduate Thesis
No
Type of Trial
Interventional
Type of Study
Drug
Study Design
Randomized, Parallel Group, Active Controlled Trial
Public Title of Study
Comparative study of effect of Remogliflozin and Empagliflozin on parameters of heart failure.
Scientific Title of Study
A prospective multicenter randomized open label active controlled study to assess effect of Remogliflozin on biomarkers of heart failure compared to Empagliflozin in patients of type 2 diabetes mellitus with chronic heart failure.
Trial Acronym
REMIT-HF
Secondary IDs if Any
Secondary ID
Identifier
IIS/2019/04 Version 2.0 dated 20-Jan-2020
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
No. 17/751, Chittur Road, Durga Nagar, Kenathuparambu, Kunathurmedu, Palakkad,
Kerala 678013, India Palakkad KERALA
9847023777
jaigopallakshmi@gmail.com
Dr Mahesh K Shah
MK Heart Centre
1st floor Vaibhav apartment S V Road, Opp Kotak Bank, near Irla Bus-stop/petrol-pump, Vile Parle (W). Mumbai, Maharashtra- 400056 Mumbai (Suburban) MAHARASHTRA
9820033827
mkheart@hotmail.com
Dr Naveen Jamwal
Ram Manohar Lohia Institute of Medical Science
Department of Cardiology, Dr. Ram Manohar Lohia Institute of Medical Science, Vibhuti Khand, Gomti Nagar, Lucknow Lucknow UTTAR PRADESH
9415112357
drjamwal@yahoo.com
Dr Shantanu Sengupta
Sengupta Hospital and Research Institute
Department of Cardiology, Ravinagar Square, Nagpur – 440033 Nagpur MAHARASHTRA
9923190925
senguptasp@gmail.com
Dr Ashwani Mehta
Sir Gangaram Hospital
Cardiac Research Room,
First floor, Near Male General Ward,
Sir Ganga ram hospital, Rajinder Nagar,
New Delhi -110060 Central DELHI
9811057384
drashwanimehta@gmail.com
Dr JPS Sawhney
Sir Gangaram Hospital
Cardiac Research Room,
First floor, Near Male General Ward,
Sir Ganga ram hospital, Rajinder Nagar,
New Delhi -110060 Central DELHI
9810059773
jpssawhney@yahoo.com
Dr Satish Suryavanshi
SMC Heart Institute
SMC Heart Institute, Vip estate, Vidhan Sabha Rd, near ashoka ratan, Raipur, Chhattisgarh 492001 Raipur CHHATTISGARH
6263014909
drsatish_suryavanshi@yahoo.co.in
Dr Mardikar
Spandan heart institute
Spandan Heart Institute & research Center,
31, Off Chitale Marg,
Dhantoli, Nagpur-440012. Nagpur MAHARASHTRA
1. Adults (≥ 18 years) of either gender diagnosed with Type-2 Diabetes Mellitus more than 6 months back
2. Having uncontrolled glycaemia (HbA1c >6.5 & <9.0%) with no change in anti-diabetic treatment therapy since last 8 weeks
3. With comorbid Chronic heart failure diagnosed at least 3 months prior to screening & in NYHA HF Class I to III during screening) without change in NYHA functional classification prior to randomization
4. Having reported reduced EF (defined as LVEF <40%) as per local reading (obtained under stable condition by echocardiography, radionuclide ventriculography, invasive angiography, MRI or CT) measured within 6 months from the screening visit.
5. Having elevated NT-proBNP levels >600 pg/mL (or >1200 pg/mL in patients with AF) analysed at central Appropriate dose of medical therapy (such as ACEi, ARB, β-blocker, oral diuretics, MRA, ARNI, ivabradine) and/or appropriate device therapy, consistent with prevailing CV guidelines & local practice, stable for at least 3 week prior to Visit 1(screening) and during screening period until Visit 2 (Randomisation) with the exception of diuretics stable for only one week prior to Visit 2 to control symptoms.
6. Patients who understand & willing to comply with study requirements and provide written informed consent for participation
ExclusionCriteria
Details
1. Patients who are being treated or have been treated with SGLT2i in past 12 weeks
2. Patients with evidence of Myocardial infarction, coronary artery bypass graft surgery, or other major cardiovascular surgery, stroke or TIA in past 12 weeks prior
3. Heart transplant recipient, or listed for heart transplant implanted left ventricular assist device (LVAD) at screening
4. Cardiomyopathy based on infiltrative diseases (e.g. amyloidosis), accumulation diseases (e.g. haemochromatosis, Fabry disease), muscular dystrophies, cardiomyopathy with reversible causes (e.g. stress cardiomyopathy), hypertrophic obstructive cardiomyopathy, induced by chemotherapy or peripartum or known pericardial constriction
5. Any severe (obstructive or regurgitant) valvular heart disease, expected to lead to surgery during the trial in the investigator’s opinion
6. Acute decompensated HF (exacerbation of chronic HF) requiring IV diuretics, IV, inotropes, or i.v. vasodilators, or LVAD within 1 week from discharge to Visit 1 (Screening) and during screening period until Visit 2 (Randomisation)
7. Atrial fibrillation or atrial flutter with a resting heart rate >110 bpm documented by ECG at Visit 1(Screening)
8. Untreated ventricular arrhythmia with syncope in patients without ICD documented within the 3 months prior to Visit 1
9. Implanted cardioverter defibrillator (ICD) or a cardiac resynchronization therapy (CRT) within 3 months prior to Visit 1, or if there is an intent to implant ICD or CRT within 6 months of visit 2
10. Symptomatic bradycardia or second or third degree heart block without a pacemaker after adjusting beta-blocker therapy, if appropriate
11. Systolic blood pressure (SBP) ≥ 180 mmHg at Visit 2. If SBP >150mmHg and <180mmHg at Visit 2, the patient should be receiving at least 3 antihypertensive drugs
12. Symptomatic hypotension and/or a SBP < 100 mmHg at Visit 1 or Visit 2
13. Type 1 diabetes mellitus
14. History of diabetic ketoacidosis, diabetic coma, or hypoglycemic attack ≤6 months prior to screening
15. Patients with eGFR <60 ml/min/1.73 m2
16. Patients with severe organ system disorders viz. Hepatic, Renal, Neoplastic, Neurological or Psychiatric disorders.
17. Patients with planned surgery in next 24 weeks or has undergone major operative procedure in past 3 months
18. CHF (NYHA functional classification IV)
19. Patients with pituitary or adrenal dysfunction
20. Patients with malnutrition, starvation, irregular eating pattern, lack of dietary intake, or debilitation or with a gastrointestinal disorder, such as diarrhea or vomiting, or Gastrointestinal surgery that could interfere with trial medication absorption in the investigator’s opinion
21. Patients with low or high body weight (BMI <18.5 kg/m2 or >45 kg/m2)
22. History of hypersensitivity to ingredients of SGLT2 inhibitors
23. Pregnant or suspected pregnancy in females, Lactating females & Patients of child bearing potential not willing to use effective non-hormonal method of contraception
24. Patients with severe infection or trauma at trial screening
25. Considered inappropriate for the study by investigators due to other reasons
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
Not Applicable
Blinding/Masking
Open Label
Primary Outcome
Outcome
TimePoints
Mean percentage change from baseline in NT-proBNP level
After 24 weeks of treatment
Secondary Outcome
Outcome
TimePoints
Mean percentage change from baseline in NT-proBNP level
After 4 and 12 weeks of treatment
Mean change from baseline in ECHO parameters (LV Size and Volume, LA size and Volume, E/e’, LVEF, LV GLS, Grade of Diastolic dysfunction, PA pressure)
After 24 weeks of treatment
Change in proportion of patients in NYHA functional classification
From baseline to 12 weeks and 24 weeks
Proportion of patients with incidence of any major adverse CV events viz. non-fatal MI, non-fatal stroke, hospitalization for HF, CV-related death
24 weeks
Mean change from baseline in HbA1c, FPG levels, PPG levels, Body weight, Waist circumference
Week 12 and 24
Proportion of patients achieving good glycemic control (HbA1c≤7%)
After 24 weeks
Mean change from baseline in Lipid profile, Systolic and diastolic blood pressure
Week 12 and 24
Mean change from baseline renal function parameters (eGFR, UPCR, Sr. Creatinine, Sr. BUN, Sr Uric acid)
24 weeks
Incidence of treatment emergent adverse events (TEAEs) assessed by any abnormal symptom, clinical signs or laboratory value
24 weeks
Target Sample Size
Total Sample Size="250" Sample Size from India="250" 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
This is a prospective, multicenter, randomized open-label, active controlled study. 250 patients of T2DM with CHF will be enrolled in the study. Patients would be randomised under 2 arms- Remogliflozin and Empagliflozin and would be followed for 24 weeks. Mean change in NT proBNP, changes in ECHO parameters, NYHA functional classification will be evaluated from baseline till Week 24