SGLT-2 Inhibitors in the Treatment of Ascites

NCT05999773 | Active Not Recruiting

• 1 other identifier: ASLG01
• Study Type: observational
• Target: 40
• Locations: 1 country
• Sites: 2

Brief Summary

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:

1. 1.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.
2. 2.Demonstrate better control of the glycemic profile in cirrhotic diabetic patients using SGLT-2 inhibitors.

Conditions

Ascites Hepatic; Cirrhosis, Liver; Diabete Type 2

Keywords

Ascites; Liver Cirrhosis; Diabete Type 2; Sodium Glucose Cotransporter 2 (SGLT-2) Inhibitors; Glyphozines

Outcome Measures

Primary Outcomes (3)

• Ascites control

  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.

  Day 0, 4 weeks, 3 months, 6 months

• Glycemic control

  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%

  Day 0, 4 weeks, 3 months, 6 months

• SGLT-2 inhibitors related adverse events

  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.

  Day 0, 4 weeks, 3 months, 6 months

Secondary Outcomes (15)

• Fasting glucose control

  Day 0, 4 weeks, 3 months, 6 months

• 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

Study Arms (2)

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.

Drug: SGLT2 inhibitor

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.

Interventions

SGLT2 inhibitor DRUG

Start of SGLT-2 inhibitors to treat diabetes according diabetology indications.

SGLT-2i Group

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

We will enroll subjects with complicated liver cirrhosis and type II diabetes mellitus consecutively, in two centers: Internal Medicine Unit of the "Policlinico Paolo Giaccone", University Hospital of Palermo, Italy and Internal Medicine Unit of the "Ospedali Riuniti Villa Sofia- Cervello" Hospital of Palermo, Italy. Patients will be assigned to intervention or control group according diabetology indications to start SGLT-2 inhibitors. Patients included in the two study groups will be sex, age and race matched.

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Palermo: lead
• Azienda Ospedaliera Ospedali Riuniti Villa Sofia Cervello: collaborator

Study Sites (2)

Internal Medicine Unit, V. Cervello Hospital

Palermo, Italy, 90100, Italy

Location

Department of Internal Medicine, University Hospital of Palermo

Palermo, Palermo, 90127, Italy

Location

Related Publications (9)

• Bernardi M, Moreau R, Angeli P, Schnabl B, Arroyo V. Mechanisms of decompensation and organ failure in cirrhosis: From peripheral arterial vasodilation to systemic inflammation hypothesis. J Hepatol. 2015 Nov;63(5):1272-84. doi: 10.1016/j.jhep.2015.07.004. Epub 2015 Jul 17.

  PMID: 26192220 BACKGROUND

• Angeli P, Gatta A, Caregaro L, Menon F, Sacerdoti D, Merkel C, Rondana M, de Toni R, Ruol A. Tubular site of renal sodium retention in ascitic liver cirrhosis evaluated by lithium clearance. Eur J Clin Invest. 1990 Feb;20(1):111-7. doi: 10.1111/j.1365-2362.1990.tb01800.x.

  PMID: 2108033 BACKGROUND

• Santos J, Planas R, Pardo A, Durandez R, Cabre E, Morillas RM, Granada ML, Jimenez JA, Quintero E, Gassull MA. Spironolactone alone or in combination with furosemide in the treatment of moderate ascites in nonazotemic cirrhosis. A randomized comparative study of efficacy and safety. J Hepatol. 2003 Aug;39(2):187-92. doi: 10.1016/s0168-8278(03)00188-0.

  PMID: 12873814 BACKGROUND

• Garcia-Compean D, Gonzalez-Gonzalez JA, Lavalle-Gonzalez FJ, Gonzalez-Moreno EI, Maldonado-Garza HJ, Villarreal-Perez JZ. The treatment of diabetes mellitus of patients with chronic liver disease. Ann Hepatol. 2015 Nov-Dec;14(6):780-8. doi: 10.5604/16652681.1171746.

  PMID: 26436350 BACKGROUND

• Kasichayanula S, Liu X, Zhang W, Pfister M, LaCreta FP, Boulton DW. Influence of hepatic impairment on the pharmacokinetics and safety profile of dapagliflozin: an open-label, parallel-group, single-dose study. Clin Ther. 2011 Nov;33(11):1798-808. doi: 10.1016/j.clinthera.2011.09.011. Epub 2011 Oct 26.

  PMID: 22030444 RESULT

• Montalvo-Gordon I, Chi-Cervera LA, Garcia-Tsao G. Sodium-Glucose Cotransporter 2 Inhibitors Ameliorate Ascites and Peripheral Edema in Patients With Cirrhosis and Diabetes. Hepatology. 2020 Nov;72(5):1880-1882. doi: 10.1002/hep.31270. No abstract available.

  PMID: 32294260 RESULT

• Kalambokis GN, Tsiakas I, Filippas-Ntekuan S, Christaki M, Despotis G, Milionis H. Empagliflozin Eliminates Refractory Ascites and Hepatic Hydrothorax in a Patient With Primary Biliary Cirrhosis. Am J Gastroenterol. 2021 Mar 1;116(3):618-619. doi: 10.14309/ajg.0000000000000995. No abstract available.

  PMID: 33027081 RESULT

• Saffo S, Taddei T. SGLT2 inhibitors and cirrhosis: A unique perspective on the comanagement of diabetes mellitus and ascites. Clin Liver Dis (Hoboken). 2018 Jul 26;11(6):141-144. doi: 10.1002/cld.714. eCollection 2018 Jun. No abstract available.

  PMID: 30992805 RESULT

• Gao Y, Wei L, Zhang DD, Chen Y, Hou B. SGLT2 Inhibitors: A New Dawn for Recurrent/Refractory Cirrhotic Ascites. J Clin Transl Hepatol. 2021 Dec 28;9(6):795-797. doi: 10.14218/JCTH.2021.00418. Epub 2021 Nov 26. No abstract available.

  PMID: 34966642 RESULT

MeSH Terms

Conditions

Liver Cirrhosis; Diabetes Mellitus, Type 2; Ascites

Interventions

Sodium-Glucose Transporter 2 Inhibitors

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Hypoglycemic Agents; Physiological Effects of Drugs

Study Officials

• Lydia Giannitrapani, MD

  University of Palermo

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Medical Doctor

Study Record Dates

• First Submitted: August 11, 2023
• First Posted: August 21, 2023
• Study Start: July 15, 2023
• Primary Completion: July 15, 2025
• Study Completion (Estimated): December 31, 2026
• Last Updated: May 1, 2026

Record last verified: 2026-04

Locations

IT (2)