Cirrhosis of the liver MedDRA version: 20.0 Level: LLT Classification code 10024667 Term: Liver cirrhosis System Organ Class: 100000004871
Conditions
Interventions
Trade Name: Lipistad, filmovertrukne tabletter
Product Name: Lipistad
Product Code: 54885
Pharmaceutical Form: Tablet
INN or Proposed INN: ATORVASTATIN
CAS Number: 134523-00-5
Concentration unit: mg
Sponsors
Afsnit 360, Gastroenheden
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Patients in the age of 18 to 80 years are eligible for inclusion. - Patients with liver cirrhosis, diagnosed by liver biopsy, ultrasound or CT scan of the liver and / or clinical biochemistry compatible with cirrhosis are eligible for inclusion. - Both patients with compensated and decompensated liver disease are eligible for inclusion - In women, documented absence of pregnancy and unless in menopause commitment to use adequate contraception. - Clinically significant portal hypertension with a hepatic venous pressure gradient measured by liver vein catheterization >10 mmHg. - Ability to read and understand project information and give written, informed consent. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range 150 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 32
Exclusion criteria
Exclusion criteria: - People treated with statins within the last year. - People with liver cirrhosis, with a clinically verified infection (standard biochemistry, culture) within the last four weeks. - Pregnancy or lactation. - Hepatocellular carcinoma - HIV infection and treatment with protease inhibitors - People in whom the clinician and investigators may have reason to doubt compliance to trial medication - Clinical and biochemical signs of hepato-renal syndrome defined by current guidelines within the last 14 days - A MELD score above 23, or Child-Pugh score higher than 13. - Hepatic encephalopathy grade 2 or higher
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Add on treatment with atorvastatin 10-20 mg to standard treatment improves survival in patients with cirrhosis of any etiology. ;Secondary Objective: Add on treatment with atorvastatin 10-20 mg to standard treatment delays onset of systemic inflammation and decompensation in cirrhosis of any etiology. Atorvastatin alters macrophage activation and immune response to inflammation in the hepatic stellate cell, by altered expression in the inflammation cascade. Atorvastatin alters protein expression in the hepatic stellate cell and in Kupffer cells. Atorvastatin prevents micro-thrombosis in the small vasculature of the liver. ;Primary end point(s): - Composite endpoint of death or liver transplantation after 1.5 and 5 years. - Hospitalization with liver related complications after 1.5 and 5 years. ;Timepoint(s) of evaluation of this end point: 1.5 and 5 years | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Survival within 1.5 years. - Survival within five years. - Decompensation of liver cirrhosis - Adverse events - Time to first hospital admission due to decompensation or complications of liver cirrhosis - Numbers of episodes of decompensation - Inflammation and macrophage activation (biomarkers specified in appendix 4) - Decrease in MELD score after one year - Decrease in Child-Pugh score after one year - Frailty Index evaluated by the Life Space Assessment questionnaire (validated in Danish) and the Short Physical Performance Battery (SPPB) - Degree of inflammation by: immunohistochemistry of the stellate cell in combination with PCR analysis for specific markers of inflammation in blood serum. - Degree of inflammation in the hepatic stellate cell by: gene activation by transcriptomics of mRNA in the hepatic stellate cell, combined with protein activity by mass spectrometry proteomics - Effect of atorvastatin of hepatic stellate cell and hepatocyte liver proteome will be investigated by mass spectrometry-based proteomics. - By high-sensitivity Mass spectrometry-based proteomics, we will perform proteomics analysis of hepatic stellate cells and Kupffer cells under atorvastatin influence. - By host genetics and metagenomics assess disease progression under atorvastatin influence. - The impact of atorvastatin on the human microbiome in combination with systemic inflammation. ;Timepoint(s) of evaluation of this end point: 1.5 and 5 years | — |
Countries
Denmark
Contacts
Public ContactNina Kimer
Afsnit 360, Gastroenheden
Outcome results
None listed