Potential Role of Sodium Glucose Cotransporter 2 Inhibitors in the Treatment of Ascites in Cirrhotic Patients
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 入组人数
- 40
- 试验地点
- 4
- 主要终点
- Glycemic control
研究概览
简要总结
The goal of this observational study is to test the efficacy of glyphozines (SGLT-2 inhibitors) in the control of ascites in patients with liver cirrhosis in class A6-B9, according to the Child-Pugh classification, and type 2 diabetes mellitus. The investigators will compare patients belonging to the intervention group (A), who will be given SGLT-2 inhibitors according to diabetology indications in addition to standard medical therapy for 6, with patients of the control group (B), who will, instead, continue with the standard medical therapy for 6 months. Standard medical therapy will include dietary sodium restriction, treatment with diuretics (furosemide and spironolactone), hypoglycemic therapy (metformin, insulin, or both) and other supportive care.
The main questions aims of this study are:
- Compare the efficacy and safety of a therapeutic approach based on the administration of SGLT-2 inhibitors in addition to optimal medical therapy (MRA and loop diuretic) compared to traditional diuretic therapy only, in cirrhotic patients with saline retention and diabetes.
- Demonstrate better control of the glycemic profile in cirrhotic diabetic patients using SGLT-2 inhibitors.
详细描述
Background The occurrence of ascites and saline retention is the most common complication in patients affected by liver cirrhosis and it is associated with poor prognosis.
It is well-known that in liver cirrhosis the underlying pathogenetic events responsible of ascites are portal hypertension and splanchnic vasodilation. These mechanisms reduce the effective circulating blood volume, triggering counter-regulatory systems such as the sympathetic nervous system (SNS) and the renin-angiotensin-aldosterone system (RAAS), that leading to renal sodium and water retention.
Therefore, considering pathogenetic knowledge, the cornerstones of ascites treatment are sodium restriction and drugs such as mineralocorticoid receptor antagonists (MRA) and loop diuretics, reserving more invasive techniques, like paracentesis with administration of human albumin, for more severe patients with grade 3 ascites unresponsive to diuretics. However, even though diuretics have proven to be among the most efficient drugs in controlling ascites, patients with liver cirrhosis and ascites treated with diuretics develop adverse drug reactions in 20-40% of cases.
One of the most common comorbidities of liver cirrhosis is type-2 diabetes mellitus (DM2), which affects approximately one-third of cirrhotic patients. The connection between liver cirrhosis and DM2 is complex. DM2 can be a secondary effect or, conversely, a casual factor of liver dysfunction.
Sodium glucose cotransporter 2 inhibitors (SGLT-2i) are a relatively new class of drugs for the management of type-2 diabetes mellitus. They inhibit the reabsorption of sodium and glucose in the proximal convoluted tubule of the nephron, leading to a significant natriuresis and have proven to be effective and safe drugs for the control of the glycemic profile in patients with liver dysfunction.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age between 18 and 80 years
- •Patients diagnosed with Child-Turcotte-Pugh A6-B class Hepatic Cirrhosis (moderately impaired liver function)
- •Patients diagnosed with Hepatic Cirrhosis of viral etiology (if previous hepatitis C virus (HCV) infection they must be in Sustained Virological Response (SVR); if previous hepatitis B virus (HBV) infection they must have undetectable viral genome)
- •Patients diagnosed with hepatic cirrhosis of metabolic etiology
- •Patients diagnosed with liver cirrhosis of alcoholic etiology (non active potus)
- •Patients with grade 1 ascites: ascites detectable only ultrasound that can be fully mobilized or controlled with diuretic therapy associated with or without moderate dietary sodium restriction
- •Grade 2 ascites: ascites that leads to a moderate abdominal distension and that recurs on at least 3 occasions within a 12-month period despite sodium restriction and adequate diuretic therapy (23)
- •Patients diagnosed with type II diabetes mellitus defined according to 2022 American Diabetes Association (ADA) guidelines.
排除标准
- •Inability to obtain informed consent
- •Ascites of non-cirrhotic origin
- •Patients diagnosed with heart failure Heart (NYHA) class => 2
- •Patients diagnosed with acute renal failure
- •Patients diagnosed with chronic renal failure and glomerular filtration rate (eGFR) below 25ml/min
- •Patients with hepatocellular carcinoma (diagnosed according to the Barcelona criteria) or other active tumors (25)
- •Grade 3 ascites: ascites that causes marked distention of the abdomen and that cannot be mobilized or whose early recurrence (i.e. after large volume paracentesis) cannot be satisfactorily prevented by medical therapy
- •Patients diagnosed with acute Spontaneous Bacterial Peritonitis (26)
- •Patients diagnosed with severe hepatic encephalopathy
- •Patients diagnosed with autoimmune diseases on active steroid treatment
- •Patients diagnosed with liver cirrhosis due to storage diseases
- •Patients diagnosed with cirrhosis of the liver due to enzyme deficiency
- •Patients diagnosed with complete portal thrombosis
- •Patients with active sepsis
- •Pregnant or breastfeeding women
- •Patients who use drugs
- •Patients with active alcohol consumption
研究组 & 干预措施
SGLT-2i Group
Patients diagnosed with Child-Turcotte-Pugh A6-B9 class Hepatic Cirrhosis (moderately impaired liver function) and type 2 Diabetes Mellitus assigned to start SGLT-2 inhibitors intake, according diabetology indications, in addition to standard medical therapy for 6 months.
干预措施: SGLT2 inhibitor (Drug)
Standard Therapy Group
Patients diagnosed with Child-Turcotte-Pugh A6-B9 class Hepatic Cirrhosis (moderately impaired liver function) and type 2 Diabetes Mellitus assigned to continue standard medical therapy, according diabetology indications, for 6 months.
结局指标
主要结局
Glycemic control
时间窗: Day 0, 4 weeks, 3 months, 6 months
Reduction of glycosylated hemoglobin (HbA1C) levels from baseline to the end of the study, defined as: * Optimal control: HbA1C below 6.5% * Good control: HbA1C between 6.5% and 6.9% * Inadequate control: HbA1C between 7.0% and 8% * Poor control: HbA1C above 8.0%
Ascites control
时间窗: Day 0, 4 weeks, 3 months, 6 months
Ascites control, defined in terms of: * Optimal control, in case of total disappearance of the ascites * Reduction of the grade of ascites from grade 2 to grade 1 (i.e. ascites that is clinically undetectable, which does not determine abdominal distension and detectable only by ultrasound). * Absence of response, in case of persistence of ascites of the same degree.
SGLT-2 inhibitors related adverse events
时间窗: Day 0, 4 weeks, 3 months, 6 months
Appearance of any adverse effect related to the intake of an SGLT-2 inhibitor, classified as follows: * None: no adverse effects * Minimal: adverse effect which does not significantly compromise the patient's state of health and which allows the continuation of the therapy * Moderate: adverse effect which significantly compromises the patient's state of health and which does not allow the continuation of the therapy, managed in an outpatient setting. * Severe: adverse effect which significantly compromises the patient's state of health and which does not allow the continuation of the therapy, managed in an inpatient setting. * Life-threatening: adverse effect that puts the patient's life in danger and which requires the immediate interruption of therapy and hospitalization.
次要结局
- Weight loss(Day 0, 4 weeks, 3 months, 6 months)
- 24-hour diuresis(Day 0, 4 weeks, 3 months, 6 months)
- Sodium excretion in the urine(From day 0 to day 180)
- Natremia(Day 0, 4 weeks, 3 months, 6 months)
- Mean arterial pressure(Day 0, 4 weeks, 3 months, 6 months)
- Glomerular filtration rate(Day 0, 4 weeks, 3 months, 6 months)
- Child-Turcotte-Pugh (CTP) score(Day 0, 4 weeks, 3 months, 6 months)
- Survival(6 months)
- Loop diuretics posology(Day 0, 4 weeks, 3 months, 6 months)
- Mineralocorticoid receptor antagonists posology(Day 0, 4 weeks, 3 months, 6 months)
- Metformin posology(Day 0, 4 weeks, 3 months, 6 months)
- Insulin bolus posology(Day 0, 4 weeks, 3 months, 6 months)
- Insulin basal posology(Day 0, 4 weeks, 3 months, 6 months)
- Adverse events classification(4 weeks, 3 months, 6 months)
- Fasting glucose control(Day 0, 4 weeks, 3 months, 6 months)
研究者
Aurelio Seidita
Medical Doctor
University of Palermo