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
  Purpose

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.


Condition
Liver Cirrhosis

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: The Predictive Utility of the Dimethylarginines and Ischemia Modified Albumin as Prognostic Biomarkers in Patients With Acute-on-chronic Liver Failure

Resource links provided by NLM:


Further study details as provided by University College London Hospitals:

Primary Outcome Measures:
  • Progress to ACLF [ Time Frame: hours, days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Prognosticate ACLF [ Time Frame: Days ] [ Designated as safety issue: No ]

Biospecimen Retention:   Samples With DNA

RNA


Estimated Enrollment: 700
Study Start Date: September 2008
Estimated Study Completion Date: November 2010
Estimated Primary Completion Date: November 2010 (Final data collection date for primary outcome measure)
Groups/Cohorts
Acute decompensation of cirrhosis
acute decompensation of liver function occuring secondary to precipitating events such as sepsis, GI bleed.

Detailed 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population

Inpatients with acute clinical deterioration of cirrhosis.

Criteria

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
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01071746

Contacts
Contact: Rajeshwar P Mookerjee, BScMRCPPhD 02076796516 r.mookerjee@ucl.ac.uk
Contact: Naina Shah, MBBSMRCP 02076796516 naina.shah@ucl.ac.uk

Locations
United Kingdom
University College London Hospital Recruiting
London, United Kingdom, WC1E 6HX
Contact: Rajeshwar P Mookerjee, BScMRCPPhD    02076796516      
Contact: Naina Shah, MBBSMRCP    02076796516      
Sponsors and Collaborators
University College London Hospitals
Medical Research Council
Investigators
Principal Investigator: Rajeshwar P Mookerjee, BScMRCPPhD University College London Hospital
  More Information

No publications provided

Responsible Party: Dr Rajeshwar P Mookerjee, University College London Hospitals
ClinicalTrials.gov Identifier: NCT01071746     History of Changes
Other Study ID Numbers: 08/HO714/8
Study First Received: February 18, 2010
Last Updated: February 18, 2010
Health Authority: United Kingdom: Research Ethics Committee

Additional relevant MeSH terms:
Liver Cirrhosis
Liver Failure
End Stage Liver Disease
Liver Diseases
Digestive System Diseases
Hepatic Insufficiency

ClinicalTrials.gov processed this record on September 16, 2014