Predictive Utility of DASIMAR as a Prognostic Biomarker in Acute-on-chronic Liver Failure (ACLF)

Liver Cirrhosis Clinical Trial

— DASIMAR  

Official title:

The Predictive Utility of the Dimethylarginines and Ischemia Modified Albumin as Prognostic Biomarkers in Patients With Acute-on-chronic Liver Failure

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01071746
• Other study ID #: 08/HO714/8
• Status: Recruiting
• Phase: N/A
• First received: February 18, 2010
• Last updated: February 18, 2010
• Start date: September 2008
• Est. completion date: November 2010

Study information

• Verified date: April 2008
• Source: University College London Hospitals
• Contact: Rajeshwar P Mookerjee, BScMRCPPhD
• Phone: 02076796516
• Email: r.mookerjee[@]ucl.ac.uk
• Is FDA regulated: No
• Health authority: United Kingdom: Research Ethics Committee
• Study type: Observational

Clinical Trial Summary

Patients with acute on chronic liver failure have a risk of developing multiorgan failure and a high mortality. The current scoring systems defining the outcome of patients with acute decompensation of cirrhosis fail to identify patients that progress to Acute-on-chronic liver failure (ACLF).

The aim of the study is to evaluate if one can identify these patients early on with the proposed biomarkers: dimethylarginines and ischemia modified albumin.

Description:

Patients with acute-on-chronic liver failure (ACLF) are at risk of multiorgan failure and high mortality. Recent data suggest that patients with decompensated liver cirrhosis have higher ADMA (asymmetrical dimethylarginine) levels compared to compensated cirrhosis and plasma ADMA levels correlate with severity of liver dysfunction and inflammation. There is also an increase in symmetric dimethylarginine (SDMA), a stereo-isomer of ADMA, which is largely excreted by the kidney. Plasma SDMA levels have been shown to be associated with patients

progressing to renal failure. In a pilot study by our group involving 52 patients with acute decompensation of chronic liver disease, we showed an increase in the summed product of ADMA and SDMA, which we termed dimethylarginine score ('DAS'): This was shown to have a good predictive utility for outcome in this small group of patients (AUROC=0.89).

Furthermore, we and others have shown that albumin of patients with advanced liver disease has widespread abnormalities. The amount of albumin that is found to have reduced metal binding capacity as a consequence of oxidative damage is termed Ischemia Modified Albumin (IMA).

Our data shows that patients with ACLF who die have a significantly increased IMA/serum albumin ratio (IMAR). The summation of these two pathologically relevant biomarkers (DAS+IMAR) we termed DASIMAR and found this score to have a better predictive utility than DAS alone (AUROC:0.91).

Primary objective : To identify the patients early on that progress to ACLF which would facilitate a goal directed therapeutic approach.

Secondary objective : Generation of this dataset will further define and enable prognostication of ACLF. If this study reveals a role for these biomarkers in patients with ACLF, commercial development of simple kits may be possible.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 700
• Est. completion date: November 2010
• Est. primary completion date: November 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• All patients with an acute clinical decompensation of presumed cirrhosis (elevated bilirubin >85 µmol/L, or/and increasing ascites or/and hepatic encephalopathy < grade 2) related to a clear precipitating event (e.g. infection, bleeding, alcoholic hepatitis, exposure to hepatotoxin)

Exclusion Criteria:

• Admission for reasons other than decompensation of cirrhosis (other co-morbid diseases, especially established cardiovascular or renal disease (U/S).

• Malignancy (extra-hepatic or a hepatocellular carcinoma).

• Patients who have undergone major surgery or have unsolved surgical problems.

• Pregnancy

Study Design

Observational Model: Cohort, Time Perspective: Prospective

Related Conditions & MeSH terms

• End Stage Liver Disease
• Liver Cirrhosis
• Liver Failure

Locations

Country	Name	City	State
United Kingdom	University College London Hospital	London

Sponsors (2)

Lead Sponsor	Collaborator
University College London Hospitals	Medical Research Council

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progress to ACLF		hours, days	No
Secondary	Prognosticate ACLF		Days	No