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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified April 2008 by University College London Hospitals.
Recruitment status was  Recruiting
Sponsor:
Collaborator:
Medical Research Council
Information provided by:
University College London Hospitals
ClinicalTrials.gov Identifier:
NCT01071746
First received: February 18, 2010
Last updated: NA
Last verified: April 2008
History: No changes posted

February 18, 2010
February 18, 2010
September 2008
November 2010   (final data collection date for primary outcome measure)
Progress to ACLF [ Time Frame: hours, days ] [ Designated as safety issue: No ]
Same as current
No Changes Posted
Prognosticate ACLF [ Time Frame: Days ] [ Designated as safety issue: No ]
Same as current
Not Provided
Not Provided
 
Predictive Utility of DASIMAR as a Prognostic Biomarker in Acute-on-chronic Liver Failure (ACLF)
The Predictive Utility of the Dimethylarginines and Ischemia Modified Albumin as Prognostic Biomarkers in Patients With Acute-on-chronic Liver Failure

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.

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.

Observational
Observational Model: Cohort
Time Perspective: Prospective
Not Provided
Retention:   Samples With DNA
Description:

RNA

Probability Sample

Inpatients with acute clinical deterioration of cirrhosis.

Liver Cirrhosis
Not Provided
Acute decompensation of cirrhosis
acute decompensation of liver function occuring secondary to precipitating events such as sepsis, GI bleed.
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
700
November 2010
November 2010   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact: Rajeshwar P Mookerjee, BScMRCPPhD 02076796516 r.mookerjee@ucl.ac.uk
Contact: Naina Shah, MBBSMRCP 02076796516 naina.shah@ucl.ac.uk
United Kingdom
 
NCT01071746
08/HO714/8
No
Dr Rajeshwar P Mookerjee, University College London Hospitals
University College London Hospitals
Medical Research Council
Principal Investigator: Rajeshwar P Mookerjee, BScMRCPPhD University College London Hospital
University College London Hospitals
April 2008

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP