DAPAGLIFLOZIN for Decompensated liver cirrhosis | Liver cirrhosis

Inclusion criteria

• {"criterion_text":"- Age between 18 and 85 years\n- Diagnosis of liver cirrhosis, documented on the basis of histological examination and/or clinical and/or instrumental examinations (ultrasonography, CT scan or liver elastography > 15 kPa)\n- Liver cirrhosis decompensation (overt hepatic encephalopathy, clinically significant ascites, hemorrhage from esophageal varices) developed within the past 12 months"}

Exclusion criteria

• {"criterion_text":"- Established hypersensitivity to Dapaglifozin\n- Patient who is a carrier of TIPS\n- Active therapy for HCV eradication with Direct Antiviral Agents or terminated < 6 months before\n- Therapy for HBV suppression with nucleoside/nucleotide analogs started < 6 months before\n- Active alcohol consumption greater than 21 weekly alcohol units\n- Presence of at least one episode of acute kidney injury (AKI) in the 4 weeks prior to enrollment\n- Presence of two or more episodes of urinary tract infection in the 12 months prior to enrollment\n- Presence of >2 episodes of \"overt\" hepatic encephalopathy in the 12 months prior to enrollment\n- Body mass index (BMI) < 20 kg/m^2\n- History of prior solid organ transplantation\n- Inclusion in other clinical trials in the month prior to study initiation\n- Ongoing therapy with SGLT2 inhibitors (Dapagliflozin, Empagliflozin, Canagliflozin, Ertugliflozin etc)\n- Presence of mental incapacity, complete language barrier, poor social support, or other reasons that, in the opinion of the investigator, may preclude the proper conduct of the study\n- Refusal or inability to sign informed consent and absence of a legal guardian capable of signing consent.\n- Pregnancy or breastfeeding (in the case of women of childbearing age, they will be asked to maintain effective contraception or, alternatively, abstention from sexual intercourse during the observation period)\n- Hepatocarcinoma outside the Milan criteria (a single nodule<5 cm or multiple nodules [maximum 3], the largest of which ≤3 cm)\n- Active extrahepatic malignancy\n- Chronic kidney disease with estimated VFG < 30 ml/min/1.73m2\n- Other known extrahepatic diseases of severe grade (e.g., heart failure NYHA class ≥ 3; COPD GOLD class ≥ 3; psychiatric disorders);\n- Diagnosis oftype 1 Diabetes Mellitus and/or previous history of diabetic ketoacidosis\n- Ascites refractory to diuretic therapy according to International Club of Ascites criteria"}

Primary endpoints

• {"endpoint_text":"- Incidence of global adverse events and incidence of serious adverse events.","definition_or_measurement_approach":""}

Secondary endpoints

• {"endpoint_text":"- Composite endpoints of further decompensation of cirrhosis (occurrence of variceal bleeding, hepatic encephalopathy, new-onset ascites or recurrent ascites, hepatorenal syndrome, spontaneous bacterial peritonitis) and death assessed at day 28 (± 7), 56 (± 7), 84 (± 7), 112 (± 7), 140 (± 7), and 168 (± 7)","definition_or_measurement_approach":"Assessed at day 28 (±7), 56 (±7), 84 (±7), 112 (±7), 140 (±7), and 168 (±7). Composite of listed clinical events and death."}
• {"endpoint_text":"- Incidence of new onset ascites","definition_or_measurement_approach":""}
• {"endpoint_text":"- Incidence of recurrent ascites","definition_or_measurement_approach":""}
• {"endpoint_text":"- Incidence of hepatic encephalopathy","definition_or_measurement_approach":""}
• {"endpoint_text":"- Incidence of variceal bleeding","definition_or_measurement_approach":""}
• {"endpoint_text":"- Incidence of hepatorenal syndrome","definition_or_measurement_approach":""}
• {"endpoint_text":"- Incdencde of spontaneous bacterial peritonitis","definition_or_measurement_approach":""}
• {"endpoint_text":"- Change from baseline in MELD score, MELD-Na score, and Child-Pugh score at day 28 (± 7), 56 (± 7), 84 (± 7), 112 (± 7), 140 (± 7), and 168 (± 7)","definition_or_measurement_approach":"Change from baseline; assessed at day 28 (±7), 56 (±7), 84 (±7), 112 (±7), 140 (±7), and 168 (±7)."}
• {"endpoint_text":"- Change in EQ-5D quality of life questionnaire score at day 84 (± 7) and 168 (± 7)","definition_or_measurement_approach":"Change from baseline in EQ-5D score; assessed at day 84 (±7) and day 168 (±7)."}
• {"endpoint_text":"- Change in Liver Frailty index at day 28 (± 7), 56 (± 7), 84 (± 7), 112 (± 7), 140 (± 7) and 168 (± 7)","definition_or_measurement_approach":"Change from baseline in Liver Frailty index; assessed at days 28, 56, 84, 112, 140, and 168 (±7 days)."}
• {"endpoint_text":"- Change from baseline in creatinine and estimated glomerular filtrate values at day 28 (± 7), 56 (± 7), 84 (± 7), 112 (± 7), 140 (± 7) and 168 (± 7)","definition_or_measurement_approach":"Change from baseline in serum creatinine and eGFR; assessed at days 28, 56, 84, 112, 140, and 168 (±7 days)."}
• {"endpoint_text":"- Incidence of acute over chronic liver failure","definition_or_measurement_approach":""}
• {"endpoint_text":"- Change from baseline in 24-hour sodiuria at day 28 (± 7), day 84 (± 7) and 168 (± 7).","definition_or_measurement_approach":"Change from baseline in 24-hour urinary sodium; assessed at day 28 (±7), day 84 (±7) and day 168 (±7)."}
• {"endpoint_text":"- Change from baseline in body weight at day 28 (± 7), 56 (± 7), 84 (± 7), 112 (± 7), 140 (± 7) and 168 (± 7).","definition_or_measurement_approach":"Change from baseline in body weight; assessed at days 28, 56, 84, 112, 140 and 168 (±7 days)."}
• {"endpoint_text":"- Change from baseline in proinflammatory cytokines (IL1beta, IL6, IL8, IL10, TNF-alpha, IL1ra) at day 84 (± 7) and 168 (± 7).","definition_or_measurement_approach":"Change from baseline in listed cytokine levels; assessed at day 84 (±7) and day 168 (±7)."}
• {"endpoint_text":"- Change from baseline in markers of circulatory dysfunction (renin, aldosterone, copeptin) at day 84 (± 7) and 168 (± 7).","definition_or_measurement_approach":"Change from baseline in renin, aldosterone, copeptin; assessed at day 84 (±7) and day 168 (±7)."}
• {"endpoint_text":"- Change from baseline in markers of oxidative stress (oxidized albumin isoforms HNA1 and HNA2, thiobarbituric acid reactive substance assay) at day 84 (± 7) and 168 (± 7).","definition_or_measurement_approach":"Change from baseline in listed oxidative stress markers; assessed at day 84 (±7) and day 168 (±7)."}
• {"endpoint_text":"- Change from baseline in markers of endothelial dysfunction (von Willebrand factor) at day 84 (± 7) and 168 (± 7).","definition_or_measurement_approach":"Change from baseline in von Willebrand factor; assessed at day 84 (±7) and day 168 (±7)."}
• {"endpoint_text":"- Change from baseline in markers of liver fibrosis (PRO-C3, PRO-C6) at day 84 (± 7) and 168 (± 7),","definition_or_measurement_approach":"Change from baseline in PRO-C3 and PRO-C6; assessed at day 84 (±7) and day 168 (±7)."}
• {"endpoint_text":"- Change from baseline in biomarkers of bacterial translocation (lipopolysaccharide binding protein, LBP) at day 84 (± 7) and 168 (± 7)","definition_or_measurement_approach":"Change from baseline in LBP; assessed at day 84 (±7) and day 168 (±7)."}
• {"endpoint_text":"- Change from baseline of \"DAMPs\" biomarkers (mitochondrial DNA, HMGB1) at day 84 (± 7) and 168 (± 7)","definition_or_measurement_approach":"Change from baseline in mitochondrial DNA and HMGB1; assessed at day 84 (±7) and day 168 (±7)."}
• {"endpoint_text":"- Change from baseline in metabolites measured by untargeted metabolomics at day 84 (± 7) and 168 (± 7)","definition_or_measurement_approach":"Change from baseline in untargeted metabolomics profiles; assessed at day 84 (±7) and day 168 (±7)."}

Italy

Earliest CTIS Part Ii Submission Date

24-05-2024

Latest Decision Or Authorization Date

05-05-2025

Processing Time Days

346

Number Of Sites

3

Number Of Participants

110

Primary sponsor

Full Name

Azienda Ospedale-Universita Padova

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Italy