Dapagliflozin in Non Alcoholic Fatty Liver Disease Associated Cirrhosis and Its Role in Preventing Development of Chronic Kidney Disease. A Randomized Controlled Trial.
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 144
- 试验地点
- 1
- 主要终点
- Development of CKD at 1 yr defined as per KDIGO guidelines.
研究概览
简要总结
BACKGROUND: Dapagliflozin is a highly potent (inhibitory constant 0.55 nmol/L) and reversible SGLT2 inhibitor that is > 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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Permuted block randomization, fixed
- 盲法
- Open Label
入排标准
- 年龄范围
- 18.00 Year(s) 至 70.00 Year(s)（—）
- 性别
- All
入选标准
- •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.
排除标准
- •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.
结局指标
主要结局
Development of CKD at 1 yr defined as per KDIGO guidelines.
时间窗: 1 year
次要结局
- Improvement in eGFR at 3 months.(3,6 and 12 months)
- Development of acute kidney disease.(3,6 and 12 months)
- Development of Chronic Kidney Disase(3,6,12 months)
- Discontinuation of the drug due to adverse effects(1 year)
- Resolution of ascites - partial or complete(3,6 and 12 months)