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Statins for Prevention of Disease Progression and Hospitalization in Liver Cirrhosis (STATLiver)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04072601
Recruitment Status : Recruiting
First Posted : August 28, 2019
Last Update Posted : December 2, 2019
Sponsor:
Collaborators:
University of Copenhagen
Aarhus University Hospital
Rigshospitalet, Denmark
Information provided by (Responsible Party):
Nina Kimer, Copenhagen University Hospital, Hvidovre

Brief Summary:

In a randomized, doubleblind and placebo-controlled trial we assess both clinical and cellular effects of atorvastatin in patients with liver cirrhosis.

162 participants will be allocated to atorvastatin 10-20 mg or placebo for 18 months. Clinical outcomes of survival, hospitalizations and safety will be evaluated. Also, the trial will investigate cellular functions in the liver by mass spectrometry proteomics, and single cell transcriptomics as well as exploring atorvastatin effects on different fenotypes by metagenomics.


Condition or disease Intervention/treatment Phase
Liver Cirrhoses Drug: Placebo oral tablet Drug: Atorvastatin 10mg Phase 4

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 162 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: Allocation and randomisation is blinded. Participants are only identified by randomisation number (no group names) Allocation ratio is 1:1 All personnel and participants are blinded through the study period. All outcome assessors are blinded to treatment.
Primary Purpose: Treatment
Official Title: Statins for Prevention of Disease Progression and Hospitalization in Liver Cirrhosis: A Multi-center, Randomized, Double Blind, Placebo-controlled Trial. The STATLiver Trial
Actual Study Start Date : November 8, 2019
Estimated Primary Completion Date : December 2022
Estimated Study Completion Date : December 2028

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Cirrhosis

Arm Intervention/treatment
Experimental: Atorvastatin
Atorvastatin 10-20 mg for 18 months of treatment. Start dose is 10 mg, adjusted to 20 mg after 15-30 days if no sideeffects occurs.
Drug: Atorvastatin 10mg
Tablet, can be adjusted to 2 tablets if tolerated

Placebo Comparator: Control
Placebo of atorvastatin 10 mg, 1-2 tablets for 18 months of treatment. Start dose is 1 tablet (10 mg placebo), adjusted to 2 tablets (20 mg placebo) after 15-30 days if no side effects occurs.
Drug: Placebo oral tablet
Lactose monohydrate 50 mg, potato starch 45 mg, Gelatine 1,2 mg, Magnesium stearate 0,5, Talc 4,5 mg




Primary Outcome Measures :
  1. Composite endpoint of numbers of death or liver transplantation [ Time Frame: 1.5 years ]
  2. Number of hospitalizations with liver related complications [ Time Frame: 1.5 years ]

Secondary Outcome Measures :
  1. Patient survival [ Time Frame: 1.5 and 5 years ]
  2. Number of adverse events [ Time Frame: 1.5 years (18 months) ]
  3. Number of Patients developing decompensation of liver cirrhosis [ Time Frame: 1.5 and 5 years ]
  4. Time to first hospital admission due to decompensation or complications of liver cirrhosis [ Time Frame: 1.5 and 5 years ]
  5. Numbers of episodes of decompensation [ Time Frame: 1.5 and 5 years ]
  6. Inflammation and macrophage activation [ Time Frame: 0.5 and 1.5 years ]
    Markers of systemic inflammation (TNF-alfa, IL4, IL10, IL 18, hsCRP) and macrophage activation (CD163, surface Mannose receptor) is measured before and after intervention

  7. Change in clinical score Child-Turcotte-Pugh [ Time Frame: 0.5 and 1.5 years ]
    Child score, a sum of point given on five parameters: P-albumin, P-bilirubin, Coagulation factor II,VII,X; presence of ascites and presence of hepatic encephalopathy. Score range: 5-15 with high score predicting af worse outcome

  8. Change in clinical score [ Time Frame: 0.5, 1.5 years ]
    MELD score a calculated score including parameters of bilirubin, INR, and creatinin levels. The score is calculated using log values. Range 5->30, with a higher score indicating worse outcome for patients.

  9. Change in clinical score, Frailty Index [ Time Frame: 0.5, 1.5 years ]
    Frailty Index, a questionnaire based on patients selfperceived health and performance. This score is under development and validation during this and other trials.

  10. Change in clinical score [ Time Frame: 0.5, 1.5 years ]
    Short Physical performance battery, a combined score of three physical tests, chair.-stand, gait speed and balance. Range 0-12 points, a high score indicates better physical performance.

  11. Cell activation [ Time Frame: 0.5 years ]
    Gene activation by transcriptomics of mRNA in the hepatic stellate cell, combined with protein activity by mass spectrometry proteomics

  12. Protein activity in the hepatic stellate cell [ Time Frame: 0.5 years ]
    By high-sensitivity Mass spectrometry-based proteomics, we will perform proteomics analysis of hepatic stellate cells and Kupffer cells under atorvastatin influence

  13. Composite endpoint of numbers of death or liver transplantation [ Time Frame: 5 years ]
  14. Number of hospitalization with liver related complications [ Time Frame: 5 years ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients in the age of 18 to 80 years
  • Patients with liver cirrhosis, diagnosed by liver biopsy or ultrasound or CT scan of the liver and clinical biochemistry compatible with cirrhosis within the past 3 months.
  • 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 in Danish and give written, informed consent.

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 (EASL) within the last 14 days
  • A MELD score above 23, or Child-Pugh score higher than 13.
  • Hepatic encephalopathy grade 2 or higher

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04072601


Contacts
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Contact: Nina Kimer, PhD 45 38621968 nina.kimer@regionh.dk
Contact: Søren Møller, DmSci 45 38623568 soeren.moeller@regionh.dk

Locations
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Denmark
Gastro Unit, medical Division, University Hospital Hvidovre Recruiting
Hvidovre, Danmark, Denmark, 2650
Contact: Nina Kimer, PhD       nina.kimer@regionh.dk   
Sponsors and Collaborators
Copenhagen University Hospital, Hvidovre
University of Copenhagen
Aarhus University Hospital
Rigshospitalet, Denmark

Publications of Results:
Other Publications:

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Responsible Party: Nina Kimer, MD, PhD, Clinician Researcher, Copenhagen University Hospital, Hvidovre
ClinicalTrials.gov Identifier: NCT04072601    
Other Study ID Numbers: STATLiver2019
First Posted: August 28, 2019    Key Record Dates
Last Update Posted: December 2, 2019
Last Verified: November 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Liver Cirrhosis
Fibrosis
Disease Progression
Pathologic Processes
Liver Diseases
Digestive System Diseases
Disease Attributes
Atorvastatin
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Enzyme Inhibitors