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CTRI Number  CTRI/2023/05/052502 [Registered on: 11/05/2023] Trial Registered Prospectively
Last Modified On: 04/10/2023
Post Graduate Thesis  Yes 
Type of Trial  Interventional 
Type of Study   Drug 
Study Design  Randomized, Parallel Group, Active Controlled Trial 
Public Title of Study   Dapagliflozin (drug) in Non Alcoholic Fatty Liver Disease Associated Cirrhosis (Liver Disease).  
Scientific Title of Study   Dapagliflozin in Non Alcoholic Fatty Liver Disease Associated Cirrhosis and Its Role in Preventing Development of Chronic Kidney Disease. A Randomized Controlled Trial.  
Trial Acronym   
Secondary IDs if Any  
Secondary ID  Identifier 
None  NIL 
 
Details of Principal Investigator or overall Trial Coordinator (multi-center study)  
Name  Dr Ayush Jain 
Designation  Senior Resident,Department of hepatology 
Affiliation  Institute of Liver and Biliary Sciences 
Address  Room No 23328, Department of Hepatology, Phase II, 3rd Floor, Institute of Liver and Biliary Sciences, D-1, Vasant Kunj New Delhi-110070

South West
DELHI
110070
India 
Phone  01146300000  
Fax    
Email  jainayush2206@gmail.com  
 
Details of Contact Person
Scientific Query  
Name  Dr Rakhi Maiwall 
Designation  Additional Professor, Department of Hepatology  
Affiliation  Institute of Liver and Biliary Sciences 
Address  Room No 23328, Department of Hepatology, Phase II, 3rd Floor, Institute of Liver and Biliary Sciences, D-1, Vasant Kunj New Delhi-110070

South West
DELHI
110070
India 
Phone    
Fax    
Email  rakhi_2011@yahoo.co.in  
 
Details of Contact Person
Public Query  
Name  Dr Rakhi Maiwall 
Designation  Additional Professor, Department of Hepatology  
Affiliation  Institute of Liver and Biliary Sciences 
Address  Room No 23328, Department of Hepatology, Phase II, 3rd Floor, Institute of Liver and Biliary Sciences, D-1, Vasant Kunj New Delhi-110070

South West
DELHI
110070
India 
Phone    
Fax    
Email  rakhi_2011@yahoo.co.in  
 
Source of Monetary or Material Support  
ILBS,D-1,Vasant Kunj,New Delhi-110070. 
 
Primary Sponsor  
Name  Institute of Liver and Biliary Sciences 
Address  Institute of Liver and Biliary Sciences, D-1, Vasant Kunj New Delhi-110070 
Type of Sponsor  Research institution and hospital 
 
Details of Secondary Sponsor  
Name  Address 
NIL  NIL 
 
Countries of Recruitment     India  
Sites of Study  
No of Sites = 1  
Name of Principal Investigator  Name of Site  Site Address  Phone/Fax/Email 
Dr Ayush Jain  Institute of Liver and Biliary Sciences  Room No 23328, Department of Hepatology, Phase II, 3rd Floor.
South West
DELHI 		 01146300000

jainayush2206@gmail.com 
 
Details of Ethics Committee  
No of Ethics Committees= 1  
Name of Committee  Approval Status 
Institutional Ethics Committee, ILBS  Approved 
 
Regulatory Clearance Status from DCGI  
Status 
Not Applicable 
 
Health Condition / Problems Studied  
Health Type  Condition 
Patients  (1) ICD-10 Condition: K746||Other and unspecified cirrhosis ofliver,  
 
Intervention / Comparator Agent  
Type  Name  Details 
Intervention  Dapagliflozin with Standard Medical treatment  Name:Dapagliflozin Dose: 5mg followed by 10 mg, frequency: Once daily route of administration: Oral total duration: 1 year 
Comparator Agent  Standard Medical treatment  Standard Medical treatment 
 
Inclusion Criteria  
Age From  18.00 Year(s)
Age To  70.00 Year(s)
Gender  Both 
Details  1. Age > 18 years <70years
2. Patient with NAFLD associated cirrhosis and moderate ascites
3. Stable eGFR-( more than 60 ml per min per 1.73m2) calculated using MDRD-6 equation:
4. Valid Informed written consent

 
 
ExclusionCriteria 
Details  1. Hospitalized patients
2. CTP-C patients
3. Intrinsic/structural kidney disease, obstructive uropathy, ADPKD, Anatomic urologic defects that predispose to urinary tract infection
4. History of organ transplantation
5. Refractory Ascites
6. Type 1 DM
7. History of hypoglycemic symptoms in the last 2 months
8. Recurrent UTI
9. Patient with HCC or portal vein thrombosis
10. Receiving therapy with an SGLT2 inhibitor within 8 weeks prior to enrolment or previous intolerance of an SGLT2 inhibitor
11. History of fracture in the preceding year
12. Severe Hyponatremia (Na <125 MEq/L)
13. Pregnancy or Lactating mother
14. Receiving cytotoxic therapy, immunosuppressive therapy or other immunotherapy for primary or secondary renal disease within 6 months prior to enrolment
15. MI, unstable angina, stroke or transient ischemic attack (TIA) within 12 weeks prior to enrolment
16. Coronary revascularization (percutaneous coronary intervention [PCI] or coronary artery bypass grafting [CABG]) or valvular repair/replacement within 12 weeks prior to enrolment or is planned to undergo any of these procedures after randomization
17. Mixed ascites (additional etiology of ascites apart from portal hypertension)
18. Any severe extra hepatic condition including respiratory and cardiac failure
19. Acute-on-chronic liver failure as per the APASL criteria
20. Refusal to give consent 
 
Method of Generating Random Sequence   Permuted block randomization, fixed 
Method of Concealment   Centralized 
Blinding/Masking   Open Label 
Primary Outcome  
Outcome  TimePoints 
Development of CKD at 1 yr defined as per KDIGO guidelines.  1 year 
 
Secondary Outcome  
Outcome  TimePoints 
Development of Chronic Kidney Disase  3,6,12 months 
Improvement in eGFR at 3 months.  3,6 and 12 months 
Development of acute kidney disease.  3,6 and 12 months 
Discontinuation of the drug due to adverse effects  1 year 
Resolution of ascites - partial or complete   3,6 and 12 months 
 
Target Sample Size   Total Sample Size="144"
Sample Size from India="144" 
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" 
Phase of Trial   N/A 
Date of First Enrollment (India)   17/05/2023 
Date of Study Completion (India) Applicable only for Completed/Terminated trials 
Date of First Enrollment (Global)  Date Missing 
Date of Study Completion (Global) Applicable only for Completed/Terminated trials 
Estimated Duration of Trial   Years="1"
Months="0"
Days="0" 
Recruitment Status of Trial (Global)
Modification(s)  		 Not Applicable 
Recruitment Status of Trial (India)  Open to Recruitment 
Publication Details   None Yet 
Individual Participant Data (IPD) Sharing Statement

Will individual participant data (IPD) be shared publicly (including data dictionaries)?  

Response - NO
Brief Summary  
BACKGROUND: Dapagliflozin is a highly potent (inhibitory constant 0.55 nmol/L) and reversible SGLT2 inhibitor that is &gt; 1400 times more selective for SGLT2 than SGLT1, the main transporter responsible for glucose absorption in the gut 1-2 . Dapagliflozin-induced glucuresis in patients with T2D was associated with caloric loss and a modest reduction in bodyweight, as well as mild osmotic diuresis and transient natriuresis 3-5 SGLT2is reduce body weight by about 1 to 3 kg by loss of fat (50%–75%), body water (15%–35%), and protein and minerals (10%). Glycosuria causes a negative calorie balance. SGLT2is switch some glucose metabolism to fatty acids and ketones and increase the glucagon/insulin ratio and fat utilization.
A study published in NEJM, revealed that among patients with heart failure and a reduced ejection fraction, the risk of worsening heart failure or death from cardiovascular causes was lower among those who received dapagliflozin than among those who received placebo, regardless of the presence or absence of diabetes 6 . Dapagliflozin has also been found to be useful in patients of CKD in reduction in the risk of ≥50% decline in eGFR, ESKD, or death from renal or cardiovascular causes (DAPA CKD). A study published in translational physiology journal confirmed that SGLT2 inhibition with dapagliflozin decreases blood glucose levels and is therapeutic in slowing the progression of diabetes-associated glomerulosclerosis and liver fibrosis in type 2 diabetic db/db mice via reduced tissue inflammation and oxidative stress.
BRIEF SUMMARY: The role of Dapagliflozin in the improvement in CKD in both diabetic and non-diabetic patients has been evaluated in the past. SGLT2i have also been found to be beneficial in NAFLD patients in improving the liver function parameters. It is also known that cirrhotic patients are at a higher risk of developing CKD at 1 year when compared to non cirrhotics.
With this study we aim to study the role Dapagliflozin in cirrhotic patients in reducing thedevelopment of CKD, its impact on cirrhotic cardiomyopathy and its role in improvement of metabolic profile and liver related outcomes.
PURPOSE: Till now no study has evaluated the role of dapagliflozin in Cirrhotic patients and its role in preventing development of CKD, cirrhotic cardiomyopathy and in improvement of liver related outcomes.
 
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