Liver CirrhosisDASIMARNCT01071746
Predictive Utility of DASIMAR as a Prognostic Biomarker in Acute-on-chronic Liver Failure (ACLF)
An observational study of Liver Cirrhosis, run by University College London Hospitals at 1 site in United Kingdom.
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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Liver Cirrhosis
- How many people
- 700 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Sep 2008to Nov 2010
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Inpatients with acute clinical deterioration of cirrhosis.
Who may be able to join
- 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)
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site, 1 recruiting
- Recruiting
University College London Hospital
London, WC1E 6HX
Rajeshwar P Mookerjee, BScMRCPPhD, 02076796516
Naina Shah, MBBSMRCP, 02076796516
About this study
Official title: 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.
Read the 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.
- Conditions
- Liver Cirrhosis
- Medical subject headings
- Liver Cirrhosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Acute decompensation of cirrhosis | acute decompensation of liver function occuring secondary to precipitating events such as sepsis, GI bleed. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progress to ACLF
Measured: hours, days
Secondary outcomes (1)
Prognosticate ACLF
Measured: Days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Feb 2010 (estimated)
- Study startSep 2008
- Primary completionNov 2010 (estimated)
- Study completionNov 2010 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Liver CirrhosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 700 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University College London Hospitals
- Sponsor type
- University, hospital or other
- Collaborators
- Medical Research Council
- Investigators
- Rajeshwar P Mookerjee, BScMRCPPhD, Principal investigator, University College London Hospitals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01071746
- Sponsor's protocol ID
- 08/HO714/8
- Acronym
- DASIMAR
- Status last verified
- Apr 2008
- First submitted
- 18 Feb 2010
- Last updated
- 19 Feb 2010
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Feb 2010. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Predictive Utility of the Dimethylarginines and Ischemia Modified Albumin as Prognostic Biomarkers in Patients With Acute-on-chronic Liver Failure
- ClinicalTrials.gov ID
- NCT01071746
- Acronym / sponsor ID
- DASIMAR / 08/HO714/8
- Conditions
- Liver Cirrhosis
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 700 participants (estimated)
- Lead sponsor
- University College London HospitalsUniversity, hospital or other
- Collaborators
- Medical Research Council
- Study start
- Sep 2008
- Primary completion
- Nov 2010 (estimated)
- Study completion
- Nov 2010 (estimated)
- First posted
- 19 Feb 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Acute decompensation of cirrhosis | – | –acute decompensation of liver function occuring secondary to precipitating events such as sepsis, GI bleed. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Inpatients with acute clinical deterioration of cirrhosis.
Key inclusion criteria (1 listed)
- 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)
Key exclusion criteria (4 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Progress to ACLF
Time frame: hours, days
1 secondary outcome
Prognosticate ACLF
Time frame: Days
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Feb 2010.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Rajeshwar P Mookerjee, BScMRCPPhD principal investigator
University College London Hospitals
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Liver Cirrhosis, run by University College London Hospitals at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 19 Feb 2010. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Rajeshwar P Mookerjee, BScMRCPPhD (02076796516, r.mookerjee@ucl.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progress to ACLF (time frame: hours, days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Feb 2010.