EUCTR2021-002617-33-DE进行中（未招募）1 期
A Phase 2a, open-label, randomized, controlled, multi-center, proof of concept study, to assess the efficacy, safety and tolerability of VS-01 on top of standard of care, compared to standard of care alone, in adult patients with acute-on-chronic liver failure (ACLF) grades 1 and 2 and ascites - UNVEIL-IT
适应症
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- Versantis AG
- 入组人数
- 60
研究概览
简要总结
暂无简介。
研究设计
- 研究类型
- Interventional
入排标准
- 性别
- All
入选标准
- •1. Patients with liver cirrhosis, diagnosed by standard clinical criteria, imaging findings and/or histology with any underlying etiology;
- •2. Patients with liver cirrhosis and ACLF grade 1 or 2 (according to EASL-CLIF criteria as described in the EASL-Clinical Practice Guideline on decompensated liver cirrhosis (EASL Clinical Practice Guidelines, 2018); organ failures will be calculated based on the CLIF-C OF score) triggered by any acute insult other than those listed in the exclusion criteria:
- •ACLF grade 1 patients meeting one of the following:
- •a. Single kidney failure (serum creatinine = 2 mg/dL) without RRT +/- liver, cerebral, coagulation, circulation or respiratory dysfunction;
- •b. Liver failure (serum bilirubin = 12.0 mg/dL) with either kidney dysfunction (serum creatinine = 1.5 – < 2.0 mg/dL) and/or HE grade 1 or 2;
- •c. Coagulation failure (International Normalized Ratio [INR] = 2.5 - = 3.0) with either kidney dysfunction (serum creatinine = 1.5 - < 2.0 mg/dL) and/or HE grade 1 or 2;
- •d. Circulatory failure (dopamine =15 µg/kg/min, or epinephrine = 0.1 µg/kg/min, or norepinephrine = 0.1 µg/kg/min) with either kidney dysfunction (serum creatinine = 1.5 - < 2.0 mg/dL) and/or HE grade 1 or 2;
- •e. Brain failure (HE West Haven grade 3) + kidney dysfunction (serum creatinine = 1.5 - < 2.0 mg/dL).
- •ACLF grade 2 patients meeting one of the following:
- •f. Kidney failure (serum creatinine = 2 mg/dL) without RRT + brain failure (HE West Haven grade 3);
- •g. Liver failure (serum bilirubin = 12.0 mg/dL) + brain failure (HE West Haven grade 3);
- •h. Kidney failure (serum creatinine = 2 mg/dL) without RRT + liver failure (serum bilirubin = 12.0 mg/dL);
- •i. Coagulation failure (INR = 2.5 - =3.0) with either brain failure (HE West Haven grade 3), kidney failure without RRT, liver failure (serum bilirubin = 12.0 mg/dL) or circulatory failure (dopamine <15 µg/kg/min, or epinephrine = 0.1 µg/kg/min, or norepinephrine = 0.1 µg/kg/min);
- •j. Circulatory failure (dopamine =15 µg/kg/min, or epinephrine = 0.1 µg/kg/min, or norepinephrine = 0.1 µg/kg/min) with either kidney failure without RRT, liver failure (serum bilirubin = 12.0 mg/dL), or brain failure (HE West Haven grade 3).
- •3. Onset of ACLF not more than 96 h before SCR;
- •4. Presence of ascites requiring paracentesis;
- •5. Patients with body mass index (BMI) < 35 kg/m² (calculated on dry body weight);
- •6. Men and women = 18 and = 69 years of age on the day of signing Patient Informed Consent Document (PICD);
- •7. Informed consent:
- •a. Ability to understand the PICD and comply with the protocol and sign the PICD or a legal representative can sign the PICD on behalf of the patient in accordance with local law and institutional policy
- •b. Signed and dated PICD obtained prior to performing any study-related procedure, including SCR.
- •Are the trial subjects under 18? no
- •Number of subjects for this age range:
- •F.1.2 Adults (18-64 years) yes
- •F.1.2.1 Number of subjects for this age range 50
- •F.1.3 Elderly (>=65 years) yes
- •F.1.3.1 Number of subjects for this age range 10
排除标准
- •1. Patients with acute or sub-acute liver failure without underlying cirrhosis;
- •2. Presence of the following organ failure(s) as per the EASL-CLIF criteria and/or adapted from CLIF-C OF/CLIF-SOFA scores:
- •a. Respiratory failure as defined by Partial pressure of oxygen (PaO2)/Fraction of inspired oxygen (FiO2) = 200, or oxygen saturation (SpO2)/FiO2 = 214 or mechanical ventilation;
- •b. Coagulation failure with an INR > 3.0 or platelet count = 20 x 109/L;
- •c. Severe cardiovascular failure requiring the use of vasopressors (dopamine >15 µg/kg/min, or epinephrine > 0.1 µg/kg/min, or norepinephrine > 0.1 µg/kg/min). It should be clarified that the use of terlipressin or low-dose norepinephrine in case of hepatorenal syndrome (HRS) is not an exclusion criterion;
- •d. HE West Haven grade 4
- •3. ACLF grade 3: Presence of three or more organ failures as per EASLCLIF criteria as described in the EASL-Clinical Practice Guideline on decompensated liver cirrhosis; organ failures will be calculated based on CLIF-C OF score);
- •4. Presence of spontaneous or secondary bacterial peritonitis:
- •a. presence of neutrophils in a normally sterile body fluid (i.e., neutrophil counts > 250/mm3 in ascitic fluid);
- •5. Presence of spontaneous bacterial pleural empyema:
- •a. In case of pleural effusion, positive pleural fluid culture and increased neutrophil count of > 250/mm3 or negative pleural fluid culture and a neutrophil count of 3 > 500/mm in the absence of pneumonia;
- •6. Patients with medical history of spontaneous bacterial peritonitis over the past 4 weeks;
- •7. Known active tuberculosis, or latent tuberculosis requiring treatment;
- •8. Presence of uncontrolled severe infection at SCR or BL (patients may be enrolled provided anti-infectives have been administered for at least 24 h before SCR or 48 h before BL with an appropriate response prior to randomization):
- •a. Infections with hemodynamic instability or septic shock, such as but not limited to UTI, pneumonia, and skin/soft tissue infection;
- •b. Acute obstructive cholangitis in the presence of cholestasis, compatible symptoms (right upper quadrant pain and jaundice) and radiological data of biliary obstruction with hemodynamic instability or septic shock;
- •c. Patients with sepsis or septic shock of unknown source;
- •9. Patients with known seizure disorder;
- •10. Patients with medical history of gastro-intestinal bleeding over the past 2 weeks, acute bleeding or bleeding upon paracentesis at SCR or BL;
- •11. Contraindication for paracentesis according to the EASL Clinical Practice Guidelines 2018, and AASLD guideline on the treatment of ascites, spontaneous bacterial peritonitis and HRS-AKI for the management of patients with decompensated cirrhosis;
- •12. Coagulation disorders such as disseminated intravascular coagulation (DIC) or hemophilia;
- •13. TIPS procedure or any major abdominal surgery having occurred in the past 4 weeks prior to SCR;
- •14. Potential or known hypersensitivity to liposomes;
- •15. Potential or known risk factors for allergic/anaphylactoid like reactions (e.g., mastocytosis/elevated basal tryptase) or multiple hypersensitivities;
- •16. Patients with known porto-pulmonary hypertension (PPHT) and hepato-pulmonary syndrome;
- •17. Patients after organ transplantation receiving immunosuppressive medication;
- •18. Any severe disease considered to be potentially detrimental at the discretion of the PI. This includes but is not limited to hepatocellular carcinoma (HCC) outside Milan criteria, cholangiocarcinoma, extrahe
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