2024-511964-95-00招募中2 期
Dapagliflozin in the treatment of decompensated liver cirrhosis: phase IIb randomised, controlled clinical trial
Azienda Ospedale-Universita Padova3 个研究点 分布在 1 个国家目标入组 110 人开始时间: 2024年6月27日最近更新:
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 110
- 试验地点
- 3
- 主要终点
- Incidence of global adverse events and incidence of serious adverse events.
研究概览
简要总结
The primary objective of the study will be to evaluate the safety of dapagliflozin versus standard medical therapy in patients with decompensated liver cirrhosis.
入排标准
- 年龄范围
- 18 years 至 65+ years（65+ Years, 18-64 Years）
- 接受健康志愿者
- 否
入选标准
- •Age between 18 and 85 years
- •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)
- •Liver cirrhosis decompensation (overt hepatic encephalopathy, clinically significant ascites, hemorrhage from esophageal varices) developed within the past 12 months
排除标准
- •Established hypersensitivity to Dapaglifozin
- •Patient who is a carrier of TIPS
- •Active therapy for HCV eradication with Direct Antiviral Agents or terminated < 6 months before
- •Therapy for HBV suppression with nucleoside/nucleotide analogs started < 6 months before
- •Active alcohol consumption greater than 21 weekly alcohol units
- •Presence of at least one episode of acute kidney injury (AKI) in the 4 weeks prior to enrollment
- •Presence of two or more episodes of urinary tract infection in the 12 months prior to enrollment
- •Presence of >2 episodes of "overt" hepatic encephalopathy in the 12 months prior to enrollment
- •Body mass index (BMI) < 20 kg/m^2
- •History of prior solid organ transplantation
- •Inclusion in other clinical trials in the month prior to study initiation
- •Ongoing therapy with SGLT2 inhibitors (Dapagliflozin, Empagliflozin, Canagliflozin, Ertugliflozin etc)
- •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
- •Refusal or inability to sign informed consent and absence of a legal guardian capable of signing consent.
- •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)
- •Hepatocarcinoma outside the Milan criteria (a single nodule<5 cm or multiple nodules [maximum 3], the largest of which ≤3 cm)
- •Active extrahepatic malignancy
- •Chronic kidney disease with estimated VFG < 30 ml/min/1.73m2
- •Other known extrahepatic diseases of severe grade (e.g., heart failure NYHA class ≥ 3; COPD GOLD class ≥ 3; psychiatric disorders);
- •Diagnosis oftype 1 Diabetes Mellitus and/or previous history of diabetic ketoacidosis
- •Ascites refractory to diuretic therapy according to International Club of Ascites criteria
结局指标
主要结局
Incidence of global adverse events and incidence of serious adverse events.
Incidence of global adverse events and incidence of serious adverse events.
次要结局
- 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)
- Incidence of new onset ascites
- Incidence of recurrent ascites
- Incidence of hepatic encephalopathy
- Incidence of variceal bleeding
- Incidence of hepatorenal syndrome
- Incdencde of spontaneous bacterial peritonitis
- 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)
- Change in EQ-5D quality of life questionnaire score at day 84 (± 7) and 168 (± 7)
- Change in Liver Frailty index at day 28 (± 7), 56 (± 7), 84 (± 7), 112 (± 7), 140 (± 7) and 168 (± 7)
- 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)
- Incidence of acute over chronic liver failure
- Change from baseline in 24-hour sodiuria at day 28 (± 7), day 84 (± 7) and 168 (± 7).
- Change from baseline in body weight at day 28 (± 7), 56 (± 7), 84 (± 7), 112 (± 7), 140 (± 7) and 168 (± 7).
- Change from baseline in proinflammatory cytokines (IL1beta, IL6, IL8, IL10, TNF-alpha, IL1ra) at day 84 (± 7) and 168 (± 7).
- Change from baseline in markers of circulatory dysfunction (renin, aldosterone, copeptin) at day 84 (± 7) and 168 (± 7).
- 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).
- Change from baseline in markers of endothelial dysfunction (von Willebrand factor) at day 84 (± 7) and 168 (± 7).
- Change from baseline in markers of liver fibrosis (PRO-C3, PRO-C6) at day 84 (± 7) and 168 (± 7),
- Change from baseline in biomarkers of bacterial translocation (lipopolysaccharide binding protein, LBP) at day 84 (± 7) and 168 (± 7)
- Change from baseline of "DAMPs" biomarkers (mitochondrial DNA, HMGB1) at day 84 (± 7) and 168 (± 7)
- Change from baseline in metabolites measured by untargeted metabolomics at day 84 (± 7) and 168 (± 7)
研究者
Salvatore Silvio Piano
Scientific
Azienda Ospedale-Universita Padova
研究点 (3)
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