xml: <clinical_study>
    <!-- This xml conforms to an XML Schema at:
      https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
    <required_header>
      <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
      <link_text>Link to the current ClinicalTrials.gov record.</link_text>
      <url>https://clinicaltrials.gov/ct2/show/NCT05999773</url>
    </required_header>
    <id_info>
      <org_study_id>ASLG01</org_study_id>
      <nct_id>NCT05999773</nct_id>
    </id_info>
    <brief_title>SGLT-2 Inhibitors in the Treatment of Ascites</brief_title>
    <official_title>Potential Role of Sodium Glucose Cotransporter 2 Inhibitors in the Treatment of Ascites in Cirrhotic Patients</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>University of Palermo</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>Azienda Ospedaliera Ospedali Riuniti Villa Sofia Cervello</agency>
        <agency_class>Other</agency_class>
      </collaborator>
    </sponsors>
    <source>University of Palermo</source>
    <oversight_info>
      <has_dmc>No</has_dmc>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        The goal of this observational study is to test the efficacy of glyphozines (SGLT-2&#xD;
        inhibitors) in the control of ascites in patients with liver cirrhosis in class A6-B9,&#xD;
        according to the Child-Pugh classification, and type 2 diabetes mellitus. The investigators&#xD;
        will compare patients belonging to the intervention group (A), who will be given SGLT-2&#xD;
        inhibitors according to diabetology indications in addition to standard medical therapy for&#xD;
        6, with patients of the control group (B), who will, instead, continue with the standard&#xD;
        medical therapy for 6 months. Standard medical therapy will include dietary sodium&#xD;
        restriction, treatment with diuretics (furosemide and spironolactone), hypoglycemic therapy&#xD;
        (metformin, insulin, or both) and other supportive care.&#xD;
  &#xD;
        The main questions aims of this study are:&#xD;
  &#xD;
          1. Compare the efficacy and safety of a therapeutic approach based on the administration of&#xD;
             SGLT-2 inhibitors in addition to optimal medical therapy (MRA and loop diuretic)&#xD;
             compared to traditional diuretic therapy only, in cirrhotic patients with saline&#xD;
             retention and diabetes.&#xD;
  &#xD;
          2. Demonstrate better control of the glycemic profile in cirrhotic diabetic patients using&#xD;
             SGLT-2 inhibitors.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Background The occurrence of ascites and saline retention is the most common complication in&#xD;
        patients affected by liver cirrhosis and it is associated with poor prognosis.&#xD;
  &#xD;
        It is well-known that in liver cirrhosis the underlying pathogenetic events responsible of&#xD;
        ascites are portal hypertension and splanchnic vasodilation. These mechanisms reduce the&#xD;
        effective circulating blood volume, triggering counter-regulatory systems such as the&#xD;
        sympathetic nervous system (SNS) and the renin-angiotensin-aldosterone system (RAAS), that&#xD;
        leading to renal sodium and water retention.&#xD;
  &#xD;
        Therefore, considering pathogenetic knowledge, the cornerstones of ascites treatment are&#xD;
        sodium restriction and drugs such as mineralocorticoid receptor antagonists (MRA) and loop&#xD;
        diuretics, reserving more invasive techniques, like paracentesis with administration of human&#xD;
        albumin, for more severe patients with grade 3 ascites unresponsive to diuretics. However,&#xD;
        even though diuretics have proven to be among the most efficient drugs in controlling&#xD;
        ascites, patients with liver cirrhosis and ascites treated with diuretics develop adverse&#xD;
        drug reactions in 20-40% of cases.&#xD;
  &#xD;
        One of the most common comorbidities of liver cirrhosis is type-2 diabetes mellitus (DM2),&#xD;
        which affects approximately one-third of cirrhotic patients. The connection between liver&#xD;
        cirrhosis and DM2 is complex. DM2 can be a secondary effect or, conversely, a casual factor&#xD;
        of liver dysfunction.&#xD;
  &#xD;
        Sodium glucose cotransporter 2 inhibitors (SGLT-2i) are a relatively new class of drugs for&#xD;
        the management of type-2 diabetes mellitus. They inhibit the reabsorption of sodium and&#xD;
        glucose in the proximal convoluted tubule of the nephron, leading to a significant&#xD;
        natriuresis and have proven to be effective and safe drugs for the control of the glycemic&#xD;
        profile in patients with liver dysfunction.&#xD;
  &#xD;
        In recently published case reports, SGLT-2i have also proven to be safe and effective in&#xD;
        controlling the glycemic profile in patients with liver dysfunction. In these patients, in&#xD;
        addition to better control the glycemic profile, they led to saline retention improvement and&#xD;
        to weight loss, without inducing encephalopathy or acute kidney injury. Other studies have&#xD;
        hypothesized that, similarly to the previously demonstrated beneficial effect of glyphozines&#xD;
        in patients with acute heart failure, SGLT-2i may also lead to the improvement of complicated&#xD;
        liver cirrhosis acting as &quot;neuromodulators&quot;, suppressing the RAAS axis and inducing better&#xD;
        mobilization of ascites and reduction of saline retention.&#xD;
  &#xD;
        Currently, there are no randomized controlled trials supporting these evidences.&#xD;
  &#xD;
        In this observational study the investigators intend to evaluate the efficacy and safety of&#xD;
        SGLT-2i in cirrhotic and diabetic patients with saline retention.&#xD;
  &#xD;
        Aims&#xD;
  &#xD;
          -  Comparing the efficacy and safety of a therapeutic approach based on the administration&#xD;
             of SGLT-2i in addition to optimal medical therapy (MRA and loop diuretic) compared to&#xD;
             traditional diuretic therapy only, in cirrhotic patients with saline retention and&#xD;
             diabetes.&#xD;
  &#xD;
          -  Demonstrating better control of the glycemic profile in cirrhotic diabetic patients&#xD;
             using SGLT-2i.&#xD;
  &#xD;
        Sample and study design Our study will be a clinical, prospective, observational multicenter&#xD;
        study. The investigators will enroll subjects with complicated liver cirrhosis and type II&#xD;
        diabetes mellitus consecutively, in two centers: Internal Medicine Unit of the &quot;Policlinico&#xD;
        Paolo Giaccone&quot;, University Hospital of Palermo, Italy and Internal Medicine Unit of the&#xD;
        &quot;Ospedali Riuniti Villa Sofia- Cervello&quot; Hospital of Palermo, Italy.&#xD;
  &#xD;
        Sample size The sample size is difficult to determine as there are no studies that have&#xD;
        evaluated the efficacy of SGLT-2i treatment in addition to diuretic therapy in the patient&#xD;
        with liver cirrhosis and saline retention. To date, there are only a few case reports in the&#xD;
        literature that have demonstrated its effectiveness. Considering the prospective and pilot&#xD;
        nature of this study the investigators decided to enroll at least 40 patients.&#xD;
  &#xD;
        Study design and outcome evaluation Our project has been approved by the ethics committee of&#xD;
        the University Hospital of Palermo.&#xD;
  &#xD;
        Patients enrolled on the basis of the inclusion and exclusion criteria and who agreed to&#xD;
        enter the study, after signing the informed consent, will be assigned to intervention group&#xD;
        (group A) or control group (group B).&#xD;
  &#xD;
        Patients belonging to the intervention group (A) will be given SGLT-2 inhibitors, according&#xD;
        diabetology indications, in addition to standard medical therapy for 6 months; the patients&#xD;
        of the control group (B) will instead continue with the only standard medical therapy for 6&#xD;
        months, according diabetology indications.&#xD;
  &#xD;
        Standard medical therapy will include dietary sodium restriction, treatment with diuretics&#xD;
        (furosemide and spironolactone), hypoglycemic therapy (metformin, insulin, or both) and other&#xD;
        supportive care. Patients taking non-selective beta-blockers will continue to do.&#xD;
  &#xD;
        Patients in group A and group B will be evaluated for specific clinical and laboratory&#xD;
        parameters before the start of the study (T0) and they will subsequently be evaluated again&#xD;
        at 4 weeks, 3 months and 6 months (T1, T2, T3).&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">July 15, 2023</start_date>
    <completion_date type="Anticipated">December 31, 2024</completion_date>
    <primary_completion_date type="Anticipated">July 15, 2024</primary_completion_date>
    <study_type>Observational</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <observational_model>Case-Control</observational_model>
      <time_perspective>Prospective</time_perspective>
    </study_design_info>
    <primary_outcome>
      <measure>Ascites control</measure>
      <time_frame>Day 0, 4 weeks, 3 months, 6 months</time_frame>
      <description>Ascites control, defined in terms of:&#xD;
  Optimal control, in case of total disappearance of the ascites&#xD;
  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).&#xD;
  Absence of response, in case of persistence of ascites of the same degree.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Glycemic control</measure>
      <time_frame>Day 0, 4 weeks, 3 months, 6 months</time_frame>
      <description>Reduction of glycosylated hemoglobin (HbA1C) levels from baseline to the end of the study, defined as:&#xD;
  Optimal control: HbA1C below 6.5%&#xD;
  Good control: HbA1C between 6.5% and 6.9%&#xD;
  Inadequate control: HbA1C between 7.0% and 8%&#xD;
  Poor control: HbA1C above 8.0%</description>
    </primary_outcome>
    <primary_outcome>
      <measure>SGLT-2 inhibitors related adverse events</measure>
      <time_frame>Day 0, 4 weeks, 3 months, 6 months</time_frame>
      <description>Appearance of any adverse effect related to the intake of an SGLT-2 inhibitor, classified as follows:&#xD;
  None: no adverse effects&#xD;
  Minimal: adverse effect which does not significantly compromise the patient's state of health and which allows the continuation of the therapy&#xD;
  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.&#xD;
  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.&#xD;
  Life-threatening: adverse effect that puts the patient's life in danger and which requires the immediate interruption of therapy and hospitalization.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Fasting glucose control</measure>
      <time_frame>Day 0, 4 weeks, 3 months, 6 months</time_frame>
      <description>Fasting blood glucose will be evaluated by finger stick glucose auto measurement after overnight fasting in the 5 days preceding the outpatient visit, and will be classified as:&#xD;
  - Good fasting glucose control: average of three consecutive fasting blood glucose measurement between 80-130 mg/dl.&#xD;
  Poor glycemic control: average blood glucose measurements of three consecutive fasting blood glucose measurement &gt;130 or &lt;70 mg/dl</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Weight loss</measure>
      <time_frame>Day 0, 4 weeks, 3 months, 6 months</time_frame>
      <description>Weight reduction will be assessed by weight measurements at day 0, at 4 weeks, 3 months and 6 months, and will be classified as:&#xD;
  Optimal: weight loss &gt;= 5 kg&#xD;
  Good: 5 Kg&lt; weight loss =&lt; 2.5 Kg&#xD;
  Poor: 2.5 Kg&lt; weight loss &lt; 0 Kg&#xD;
  Gain: any value of weight gain</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>24-hour diuresis</measure>
      <time_frame>Day 0, 4 weeks, 3 months, 6 months</time_frame>
      <description>24-hours diuresis will be assessed at day 0, at 4 weeks, 3 months and 6 months and will be classified as:&#xD;
  None: no change in 24- hours urinary volume&#xD;
  Decrease: significant (p&lt;0.05) reduction of 24- hours urinary volume&#xD;
  Increase: significant (p&lt;0.05) increase of 24- hours urinary volume</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Sodium excretion in the urine</measure>
      <time_frame>From day 0 to day 180</time_frame>
      <description>Fraction of sodium excretion will be evaluated on 24-hours diuresis at day 0, at 4 weeks, 3 months and 6 months and will be classified as:&#xD;
  None: no change in 24- hours sodium excretion&#xD;
  Decrease: significant (p&lt;0.05) reduction of 24- hours sodium excretion&#xD;
  Increase: significant (p&lt;0.05) increase of 24- hours sodium excretion</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Natremia</measure>
      <time_frame>Day 0, 4 weeks, 3 months, 6 months</time_frame>
      <description>Natremia will be evaluated on plasma samples at day 0, at 4 weeks, 3 months and 6 months and will be classified as:&#xD;
  None: no change in natremia&#xD;
  Decrease: significant (p&lt;0.05) reduction of natremia&#xD;
  Increase: significant (p&lt;0.05) increase of natremia</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Mean arterial pressure</measure>
      <time_frame>Day 0, 4 weeks, 3 months, 6 months</time_frame>
      <description>Mean arterial pressure will be evaluated according international guidelines of blood pressure assessment at day 0, at 4 weeks, 3 months and 6 months and will be classified as:&#xD;
  None: no change in mean arterial pressure&#xD;
  Decrease: significant (p&lt;0.05) reduction of mean arterial pressure&#xD;
  Increase: significant (p&lt;0.05) increase of mean arterial pressure</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Glomerular filtration rate</measure>
      <time_frame>Day 0, 4 weeks, 3 months, 6 months</time_frame>
      <description>Glomerular filtration rate will be evaluated according to Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) measurement at day 0, at 4 weeks, 3 months and 6 months and will be classified as:&#xD;
  None: no change in glomerular filtration rate&#xD;
  Decrease: significant (p&lt;0.05) reduction of glomerular filtration rate&#xD;
  Increase: significant (p&lt;0.05) increase of glomerular filtration rate</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Child-Turcotte-Pugh (CTP) score</measure>
      <time_frame>Day 0, 4 weeks, 3 months, 6 months</time_frame>
      <description>CTP score will be evaluated at day 0, at 4 weeks, 3 months and 6 months and will be classified as:&#xD;
  None: no change in glomerular filtration rate&#xD;
  Reduction: decrease of at least 1 point in the CTP score&#xD;
  Increase: increase of at least 1 point in the CTP score</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Survival</measure>
      <time_frame>6 months</time_frame>
      <description>Overall patient's survival will be evaluated after 6 months from the study enrollment</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Loop diuretics posology</measure>
      <time_frame>Day 0, 4 weeks, 3 months, 6 months</time_frame>
      <description>Loop diuretics posology (mg/die) will be evaluated at day 0, at 4 weeks, 3 months and 6 months and will be classified as:&#xD;
  None: no change in loop diuretics posology to control ascites&#xD;
  Reduction: decrease of loop diuretics posology to control ascites&#xD;
  Increase: increase of loop diuretics posology to control ascites</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Mineralocorticoid receptor antagonists posology</measure>
      <time_frame>Day 0, 4 weeks, 3 months, 6 months</time_frame>
      <description>Mineralocorticoid receptor antagonists diuretics posology (mg/die) will be evaluated at day 0, at 4 weeks, 3 months and 6 months and will be classified as:&#xD;
  None: no change in mineralocorticoid receptor antagonists posology to control ascites&#xD;
  Reduction: decrease of mineralocorticoid receptor antagonists posology to control ascites&#xD;
  Increase: increase of mineralocorticoid receptor antagonists posology to control ascites</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Metformin posology</measure>
      <time_frame>Day 0, 4 weeks, 3 months, 6 months</time_frame>
      <description>Metformin (only in patients taking metformin) posology (mg/die) will be evaluated at day 0, at 4 weeks, 3 months and 6 months and will be classified as:&#xD;
  None: no change in metformin posology to control ascites&#xD;
  Reduction: decrease of metformin posology to control ascites&#xD;
  Increase: increase of metformin posology to control ascites</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Insulin bolus posology</measure>
      <time_frame>Day 0, 4 weeks, 3 months, 6 months</time_frame>
      <description>Insulin bolus (only in patients taking insulin) posology (mg/die) will be evaluated at day 0, at 4 weeks, 3 months and 6 months and will be classified as:&#xD;
  None: no change in insulin bolus posology to control ascites&#xD;
  Reduction: decrease of insulin bolus posology to control ascites&#xD;
  Increase: increase of insulin bolus posology to control ascites</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Insulin basal posology</measure>
      <time_frame>Day 0, 4 weeks, 3 months, 6 months</time_frame>
      <description>Insulin basal (only in patients taking insulin) posology (mg/die) will be evaluated at day 0, at 4 weeks, 3 months and 6 months and will be classified as:&#xD;
  None: no change in insulin basal posology to control ascites&#xD;
  Reduction: decrease of insulin basal posology to control ascites&#xD;
  Increase: increase of insulin basal posology to control ascites</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Adverse events classification</measure>
      <time_frame>4 weeks, 3 months, 6 months</time_frame>
      <description>Putative adverse events related to SGLT-2 inhibitors intake will be classified as:&#xD;
  Allergy: appearance of any allergic manifestation including: skin rash, itching, erythema, urticaria, angioedema, anaphylaxis, anaphylactic shock&#xD;
  Infectious diseases: Occurrence of any of the following conditions: Vulvovaginal candidiasis, balanitis or balanoposthitisb, urinary tract infection (including pyelonephritis and urosepsis)&#xD;
  Metabolism disorders: hypoglycemia, dehydration, diabetic ketoacidosis, dyslipidemia, hyperkalaemia, hyperphosphoraemia&#xD;
  Nervous system disorders: postural dizziness, syncope&#xD;
  Vascular disorders: hypotension, orthostatic hypotension&#xD;
  Gastrointestinal disorders: constipation, thirst, nausea&#xD;
  Musculoskeletal system disorders: bone fracture&#xD;
  Renal and urinary disorders: polyuria, pollakiuria, renal insufficiency (mainly in the context of hypovolemia)</description>
    </secondary_outcome>
    <number_of_groups>2</number_of_groups>
    <enrollment type="Anticipated">40</enrollment>
    <condition>Ascites Hepatic</condition>
    <condition>Cirrhosis, Liver</condition>
    <condition>Diabete Type 2</condition>
    <arm_group>
      <arm_group_label>SGLT-2i Group</arm_group_label>
      <description>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.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Standard Therapy Group</arm_group_label>
      <description>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.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>SGLT2 inhibitor</intervention_name>
      <description>Start of SGLT-2 inhibitors to treat diabetes according diabetology indications.</description>
      <arm_group_label>SGLT-2i Group</arm_group_label>
    </intervention>
    <eligibility>
      <study_pop>
        <textblock>
          We will enroll subjects with complicated liver cirrhosis and type II diabetes mellitus&#xD;
          consecutively, in two centers: Internal Medicine Unit of the &quot;Policlinico Paolo Giaccone&quot;,&#xD;
          University Hospital of Palermo, Italy and Internal Medicine Unit of the &quot;Ospedali Riuniti&#xD;
          Villa Sofia- Cervello&quot; Hospital of Palermo, Italy.&#xD;
  &#xD;
          Patients will be assigned to intervention or control group according diabetology&#xD;
          indications to start SGLT-2 inhibitors.&#xD;
  &#xD;
          Patients included in the two study groups will be sex, age and race matched.&#xD;
        </textblock>
      </study_pop>
      <sampling_method>Non-Probability Sample</sampling_method>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Age between 18 and 80 years&#xD;
  &#xD;
            -  Patients diagnosed with Child-Turcotte-Pugh A6-B class Hepatic Cirrhosis (moderately&#xD;
               impaired liver function)&#xD;
  &#xD;
            -  Patients diagnosed with Hepatic Cirrhosis of viral etiology (if previous hepatitis C&#xD;
               virus (HCV) infection they must be in Sustained Virological Response (SVR); if&#xD;
               previous hepatitis B virus (HBV) infection they must have undetectable viral genome)&#xD;
  &#xD;
            -  Patients diagnosed with hepatic cirrhosis of metabolic etiology&#xD;
  &#xD;
            -  Patients diagnosed with liver cirrhosis of alcoholic etiology (non active potus)&#xD;
  &#xD;
            -  Patients with grade 1 ascites: ascites detectable only ultrasound that can be fully&#xD;
               mobilized or controlled with diuretic therapy associated with or without moderate&#xD;
               dietary sodium restriction&#xD;
  &#xD;
            -  Grade 2 ascites: ascites that leads to a moderate abdominal distension and that recurs&#xD;
               on at least 3 occasions within a 12-month period despite sodium restriction and&#xD;
               adequate diuretic therapy (23)&#xD;
  &#xD;
            -  Patients diagnosed with type II diabetes mellitus defined according to 2022 American&#xD;
               Diabetes Association (ADA) guidelines.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Inability to obtain informed consent&#xD;
  &#xD;
            -  Ascites of non-cirrhotic origin&#xD;
  &#xD;
            -  Patients diagnosed with heart failure Heart (NYHA) class =&gt; 2&#xD;
  &#xD;
            -  Patients diagnosed with acute renal failure&#xD;
  &#xD;
            -  Patients diagnosed with chronic renal failure and glomerular filtration rate (eGFR)&#xD;
               below 25ml/min&#xD;
  &#xD;
            -  Patients with hepatocellular carcinoma (diagnosed according to the Barcelona criteria)&#xD;
               or other active tumors (25)&#xD;
  &#xD;
            -  Grade 3 ascites: ascites that causes marked distention of the abdomen and that cannot&#xD;
               be mobilized or whose early recurrence (i.e. after large volume paracentesis) cannot&#xD;
               be satisfactorily prevented by medical therapy&#xD;
  &#xD;
            -  Patients diagnosed with acute Spontaneous Bacterial Peritonitis (26)&#xD;
  &#xD;
            -  Patients diagnosed with severe hepatic encephalopathy&#xD;
  &#xD;
            -  Patients diagnosed with autoimmune diseases on active steroid treatment&#xD;
  &#xD;
            -  Patients diagnosed with liver cirrhosis due to storage diseases&#xD;
  &#xD;
            -  Patients diagnosed with cirrhosis of the liver due to enzyme deficiency&#xD;
  &#xD;
            -  Patients diagnosed with complete portal thrombosis&#xD;
  &#xD;
            -  Patients with active sepsis&#xD;
  &#xD;
            -  Pregnant or breastfeeding women&#xD;
  &#xD;
            -  Patients who use drugs&#xD;
  &#xD;
            -  Patients with active alcohol consumption&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>80 Years</maximum_age>
    </eligibility>
    <overall_official>
      <last_name>Lydia Giannitrapani, MD</last_name>
      <role>Principal Investigator</role>
      <affiliation>University of Palermo</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Lydia Giannitrapani, MD</last_name>
      <phone>00390916554710</phone>
      <email>lydia.giannitrapani@unipa.it</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Aurelio Seidita, MD</last_name>
      <phone>00390916554710</phone>
      <email>aurelio.seidita@unipa.it</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>Internal Medicine Unit, V. Cervello Hospital</name>
        <address>
          <city>Palermo</city>
          <zip>90100</zip>
          <country>Italy</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Aurelio Seidita, MD</last_name>
        <phone>00390916802742</phone>
        <email>aurelio.seidita@unipa.it</email>
      </contact>
      <contact_backup>
        <last_name>Francesca Mandreucci, MD</last_name>
        <phone>00390916802742</phone>
        <email>francesca.mandreucci@gmail.com</email>
      </contact_backup>
      <investigator>
        <last_name>Aurelio Seidita, MD</last_name>
        <role>Principal Investigator</role>
      </investigator>
      <investigator>
        <last_name>Antonio Carroccio, MD</last_name>
        <role>Sub-Investigator</role>
      </investigator>
      <investigator>
        <last_name>Salvatore Madonia, MD</last_name>
        <role>Sub-Investigator</role>
      </investigator>
      <investigator>
        <last_name>Francesca Mandreucci, MD</last_name>
        <role>Sub-Investigator</role>
      </investigator>
      <investigator>
        <last_name>Giuseppe Malizia, MD</last_name>
        <role>Sub-Investigator</role>
      </investigator>
      <investigator>
        <last_name>Andrea Affronti, MD</last_name>
        <role>Sub-Investigator</role>
      </investigator>
      <investigator>
        <last_name>Fabrizio Bronte, MD</last_name>
        <role>Sub-Investigator</role>
      </investigator>
    </location>
    <location>
      <facility>
        <name>Department of Internal Medicine, University Hospital of Palermo</name>
        <address>
          <city>Palermo</city>
          <zip>90127</zip>
          <country>Italy</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Lydia Giannitrapani, MD</last_name>
        <phone>+390916554710</phone>
        <email>lydia.giannitrapani@unipa.it</email>
      </contact>
      <contact_backup>
        <last_name>Maurizio Soresi, MD</last_name>
        <phone>+390916554710</phone>
        <email>maurizio.soresi@unipa.it</email>
      </contact_backup>
      <investigator>
        <last_name>Lydia Giannitrapani, MD</last_name>
        <role>Principal Investigator</role>
      </investigator>
      <investigator>
        <last_name>Maurizio Soresi, MD</last_name>
        <role>Sub-Investigator</role>
      </investigator>
      <investigator>
        <last_name>Anna Licata, MD</last_name>
        <role>Sub-Investigator</role>
      </investigator>
      <investigator>
        <last_name>Roberto Citarrella, MD</last_name>
        <role>Sub-Investigator</role>
      </investigator>
      <investigator>
        <last_name>Mario Barbagallo, MD</last_name>
        <role>Sub-Investigator</role>
      </investigator>
      <investigator>
        <last_name>Eleonora Santangelo, MD</last_name>
        <role>Sub-Investigator</role>
      </investigator>
      <investigator>
        <last_name>Roberta Chianetta, MD</last_name>
        <role>Sub-Investigator</role>
      </investigator>
    </location>
    <location_countries>
      <country>Italy</country>
    </location_countries>
    <reference>
      <citation>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.</citation>
      <PMID>26192220</PMID>
    </reference>
    <reference>
      <citation>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.</citation>
      <PMID>2108033</PMID>
    </reference>
    <reference>
      <citation>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.</citation>
      <PMID>12873814</PMID>
    </reference>
    <reference>
      <citation>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.</citation>
      <PMID>26436350</PMID>
    </reference>
    <results_reference>
      <citation>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.</citation>
      <PMID>22030444</PMID>
    </results_reference>
    <results_reference>
      <citation>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.</citation>
      <PMID>32294260</PMID>
    </results_reference>
    <results_reference>
      <citation>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.</citation>
      <PMID>33027081</PMID>
    </results_reference>
    <results_reference>
      <citation>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.</citation>
      <PMID>30992805</PMID>
    </results_reference>
    <results_reference>
      <citation>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.</citation>
      <PMID>34966642</PMID>
    </results_reference>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 11, 2023</study_first_submitted>
    <study_first_submitted_qc>August 11, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 21, 2023</study_first_posted>
    <last_update_submitted>August 25, 2023</last_update_submitted>
    <last_update_submitted_qc>August 25, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 29, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>University of Palermo</investigator_affiliation>
      <investigator_full_name>Aurelio Seidita</investigator_full_name>
      <investigator_title>Medical Doctor</investigator_title>
    </responsible_party>
    <keyword>Ascites</keyword>
    <keyword>Liver Cirrhosis</keyword>
    <keyword>Diabete Type 2</keyword>
    <keyword>Sodium Glucose Cotransporter 2 (SGLT-2) Inhibitors</keyword>
    <keyword>Glyphozines</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Liver Cirrhosis</mesh_term>
      <mesh_term>Diabetes Mellitus, Type 2</mesh_term>
      <mesh_term>Fibrosis</mesh_term>
      <mesh_term>Ascites</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Sodium-Glucose Transporter 2 Inhibitors</mesh_term>
    </intervention_browse>
    <patient_data>
      <sharing_ipd>Undecided</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: download date: ClinicalTrials.gov processed this data on September 20, 2023
  link text: Link to the current ClinicalTrials.gov record.
  url: https://clinicaltrials.gov/ct2/show/NCT05999773
  org study id: ASLG01
  nct id: NCT05999773
  lead sponsor: 
  collaborator: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  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. 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. Demonstrate better control of the glycemic profile in cirrhotic diabetic patients using
             SGLT-2 inhibitors.
  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.
  
        In recently published case reports, SGLT-2i have also proven to be safe and effective in
        controlling the glycemic profile in patients with liver dysfunction. In these patients, in
        addition to better control the glycemic profile, they led to saline retention improvement and
        to weight loss, without inducing encephalopathy or acute kidney injury. Other studies have
        hypothesized that, similarly to the previously demonstrated beneficial effect of glyphozines
        in patients with acute heart failure, SGLT-2i may also lead to the improvement of complicated
        liver cirrhosis acting as "neuromodulators", suppressing the RAAS axis and inducing better
        mobilization of ascites and reduction of saline retention.
  
        Currently, there are no randomized controlled trials supporting these evidences.
  
        In this observational study the investigators intend to evaluate the efficacy and safety of
        SGLT-2i in cirrhotic and diabetic patients with saline retention.
  
        Aims
  
          -  Comparing the efficacy and safety of a therapeutic approach based on the administration
             of SGLT-2i in addition to optimal medical therapy (MRA and loop diuretic) compared to
             traditional diuretic therapy only, in cirrhotic patients with saline retention and
             diabetes.
  
          -  Demonstrating better control of the glycemic profile in cirrhotic diabetic patients
             using SGLT-2i.
  
        Sample and study design Our study will be a clinical, prospective, observational multicenter
        study. The investigators 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.
  
        Sample size The sample size is difficult to determine as there are no studies that have
        evaluated the efficacy of SGLT-2i treatment in addition to diuretic therapy in the patient
        with liver cirrhosis and saline retention. To date, there are only a few case reports in the
        literature that have demonstrated its effectiveness. Considering the prospective and pilot
        nature of this study the investigators decided to enroll at least 40 patients.
  
        Study design and outcome evaluation Our project has been approved by the ethics committee of
        the University Hospital of Palermo.
  
        Patients enrolled on the basis of the inclusion and exclusion criteria and who agreed to
        enter the study, after signing the informed consent, will be assigned to intervention group
        (group A) or control group (group B).
  
        Patients belonging to the intervention group (A) will be given SGLT-2 inhibitors, according
        diabetology indications, in addition to standard medical therapy for 6 months; the patients
        of the control group (B) will instead continue with the only standard medical therapy for 6
        months, according diabetology indications.
  
        Standard medical therapy will include dietary sodium restriction, treatment with diuretics
        (furosemide and spironolactone), hypoglycemic therapy (metformin, insulin, or both) and other
        supportive care. Patients taking non-selective beta-blockers will continue to do.
  
        Patients in group A and group B will be evaluated for specific clinical and laboratory
        parameters before the start of the study (T0) and they will subsequently be evaluated again
        at 4 weeks, 3 months and 6 months (T1, T2, T3).
  observational model: Case-Control
  time perspective: Prospective
  measure: Ascites control
  time frame: Day 0, 4 weeks, 3 months, 6 months
  description: 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.
  measure: Glycemic control
  time frame: Day 0, 4 weeks, 3 months, 6 months
  description: 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%
  measure: SGLT-2 inhibitors related adverse events
  time frame: Day 0, 4 weeks, 3 months, 6 months
  description: 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.
  measure: Fasting glucose control
  time frame: Day 0, 4 weeks, 3 months, 6 months
  description: Fasting blood glucose will be evaluated by finger stick glucose auto measurement after overnight fasting in the 5 days preceding the outpatient visit, and will be classified as:
  - Good fasting glucose control: average of three consecutive fasting blood glucose measurement between 80-130 mg/dl.
  Poor glycemic control: average blood glucose measurements of three consecutive fasting blood glucose measurement >130 or <70 mg/dl
  measure: Weight loss
  time frame: Day 0, 4 weeks, 3 months, 6 months
  description: Weight reduction will be assessed by weight measurements at day 0, at 4 weeks, 3 months and 6 months, and will be classified as:
  Optimal: weight loss >= 5 kg
  Good: 5 Kg< weight loss =< 2.5 Kg
  Poor: 2.5 Kg< weight loss < 0 Kg
  Gain: any value of weight gain
  measure: 24-hour diuresis
  time frame: Day 0, 4 weeks, 3 months, 6 months
  description: 24-hours diuresis will be assessed at day 0, at 4 weeks, 3 months and 6 months and will be classified as:
  None: no change in 24- hours urinary volume
  Decrease: significant (p<0.05) reduction of 24- hours urinary volume
  Increase: significant (p<0.05) increase of 24- hours urinary volume
  measure: Sodium excretion in the urine
  time frame: From day 0 to day 180
  description: Fraction of sodium excretion will be evaluated on 24-hours diuresis at day 0, at 4 weeks, 3 months and 6 months and will be classified as:
  None: no change in 24- hours sodium excretion
  Decrease: significant (p<0.05) reduction of 24- hours sodium excretion
  Increase: significant (p<0.05) increase of 24- hours sodium excretion
  measure: Natremia
  time frame: Day 0, 4 weeks, 3 months, 6 months
  description: Natremia will be evaluated on plasma samples at day 0, at 4 weeks, 3 months and 6 months and will be classified as:
  None: no change in natremia
  Decrease: significant (p<0.05) reduction of natremia
  Increase: significant (p<0.05) increase of natremia
  measure: Mean arterial pressure
  time frame: Day 0, 4 weeks, 3 months, 6 months
  description: Mean arterial pressure will be evaluated according international guidelines of blood pressure assessment at day 0, at 4 weeks, 3 months and 6 months and will be classified as:
  None: no change in mean arterial pressure
  Decrease: significant (p<0.05) reduction of mean arterial pressure
  Increase: significant (p<0.05) increase of mean arterial pressure
  measure: Glomerular filtration rate
  time frame: Day 0, 4 weeks, 3 months, 6 months
  description: Glomerular filtration rate will be evaluated according to Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) measurement at day 0, at 4 weeks, 3 months and 6 months and will be classified as:
  None: no change in glomerular filtration rate
  Decrease: significant (p<0.05) reduction of glomerular filtration rate
  Increase: significant (p<0.05) increase of glomerular filtration rate
  measure: Child-Turcotte-Pugh (CTP) score
  time frame: Day 0, 4 weeks, 3 months, 6 months
  description: CTP score will be evaluated at day 0, at 4 weeks, 3 months and 6 months and will be classified as:
  None: no change in glomerular filtration rate
  Reduction: decrease of at least 1 point in the CTP score
  Increase: increase of at least 1 point in the CTP score
  measure: Survival
  time frame: 6 months
  description: Overall patient's survival will be evaluated after 6 months from the study enrollment
  measure: Loop diuretics posology
  time frame: Day 0, 4 weeks, 3 months, 6 months
  description: Loop diuretics posology (mg/die) will be evaluated at day 0, at 4 weeks, 3 months and 6 months and will be classified as:
  None: no change in loop diuretics posology to control ascites
  Reduction: decrease of loop diuretics posology to control ascites
  Increase: increase of loop diuretics posology to control ascites
  measure: Mineralocorticoid receptor antagonists posology
  time frame: Day 0, 4 weeks, 3 months, 6 months
  description: Mineralocorticoid receptor antagonists diuretics posology (mg/die) will be evaluated at day 0, at 4 weeks, 3 months and 6 months and will be classified as:
  None: no change in mineralocorticoid receptor antagonists posology to control ascites
  Reduction: decrease of mineralocorticoid receptor antagonists posology to control ascites
  Increase: increase of mineralocorticoid receptor antagonists posology to control ascites
  measure: Metformin posology
  time frame: Day 0, 4 weeks, 3 months, 6 months
  description: Metformin (only in patients taking metformin) posology (mg/die) will be evaluated at day 0, at 4 weeks, 3 months and 6 months and will be classified as:
  None: no change in metformin posology to control ascites
  Reduction: decrease of metformin posology to control ascites
  Increase: increase of metformin posology to control ascites
  measure: Insulin bolus posology
  time frame: Day 0, 4 weeks, 3 months, 6 months
  description: Insulin bolus (only in patients taking insulin) posology (mg/die) will be evaluated at day 0, at 4 weeks, 3 months and 6 months and will be classified as:
  None: no change in insulin bolus posology to control ascites
  Reduction: decrease of insulin bolus posology to control ascites
  Increase: increase of insulin bolus posology to control ascites
  measure: Insulin basal posology
  time frame: Day 0, 4 weeks, 3 months, 6 months
  description: Insulin basal (only in patients taking insulin) posology (mg/die) will be evaluated at day 0, at 4 weeks, 3 months and 6 months and will be classified as:
  None: no change in insulin basal posology to control ascites
  Reduction: decrease of insulin basal posology to control ascites
  Increase: increase of insulin basal posology to control ascites
  measure: Adverse events classification
  time frame: 4 weeks, 3 months, 6 months
  description: Putative adverse events related to SGLT-2 inhibitors intake will be classified as:
  Allergy: appearance of any allergic manifestation including: skin rash, itching, erythema, urticaria, angioedema, anaphylaxis, anaphylactic shock
  Infectious diseases: Occurrence of any of the following conditions: Vulvovaginal candidiasis, balanitis or balanoposthitisb, urinary tract infection (including pyelonephritis and urosepsis)
  Metabolism disorders: hypoglycemia, dehydration, diabetic ketoacidosis, dyslipidemia, hyperkalaemia, hyperphosphoraemia
  Nervous system disorders: postural dizziness, syncope
  Vascular disorders: hypotension, orthostatic hypotension
  Gastrointestinal disorders: constipation, thirst, nausea
  Musculoskeletal system disorders: bone fracture
  Renal and urinary disorders: polyuria, pollakiuria, renal insufficiency (mainly in the context of hypovolemia)
  arm group label: SGLT-2i Group
  description: 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.
  arm group label: Standard Therapy Group
  description: 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.
  intervention type: Drug
  intervention name: SGLT2 inhibitor
  description: Start of SGLT-2 inhibitors to treat diabetes according diabetology indications.
  arm group label: SGLT-2i Group
  study pop: 
  sampling method: Non-Probability Sample
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 80 Years
  last name: Lydia Giannitrapani, MD
  role: Principal Investigator
  affiliation: University of Palermo
  last name: Lydia Giannitrapani, MD
  phone: 00390916554710
  email: lydia.giannitrapani@unipa.it
  last name: Aurelio Seidita, MD
  phone: 00390916554710
  email: aurelio.seidita@unipa.it
  facility: 
  status: Recruiting
  contact: 
  contact backup: 
  investigator: 
  investigator: 
  investigator: 
  investigator: 
  investigator: 
  investigator: 
  investigator: 
  facility: 
  status: Recruiting
  contact: 
  contact backup: 
  investigator: 
  investigator: 
  investigator: 
  investigator: 
  investigator: 
  investigator: 
  investigator: 
  country: Italy
  citation: 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
  citation: 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
  citation: 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
  citation: 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
  citation: 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
  citation: 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
  citation: 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
  citation: 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
  citation: 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
  responsible party type: Principal Investigator
  investigator affiliation: University of Palermo
  investigator full name: Aurelio Seidita
  investigator title: Medical Doctor
  mesh term: Liver Cirrhosis
  mesh term: Diabetes Mellitus, Type 2
  mesh term: Fibrosis
  mesh term: Ascites
  mesh term: Sodium-Glucose Transporter 2 Inhibitors
  sharing ipd: Undecided