Assessing Antibiotic Induced Liver Injury for Stratification of Tuberculosis Patients

A panel of highly sensitive circulating biomarkers for acute liver injury have been identified and demonstrated to identify liver injury on first presentation to hospital before standard tests are elevated in patients with paracetamol overdose. The investigators wish to test these biomarkers in patients with active and latent tuberculosis to see if they can be used to stratify patients undertaking anti-tuberculosis drug therapy. Anti-tuberculosis drug induced liver injury is the most frequent side-effect of anti-tuberculosis therapy, affecting 2-5% of tuberculosis patients seen at the Royal Infirmary Edinburgh and hindering their effective treatment. Patients will be recruited from the TB out-patient clinic at the Royal Infirmary Edinburgh. Blood samples will be taken every time the patient visits the clinic and also retrieved from the biochemistry lab. The biomarkers in the blood samples will be analysed to determine if they rise in patients who develop liver injury.

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Key information

Conditions

Drug-Induced Liver Injury Actinomycetales Infections Anti-Tuberculous Drug Reaction Bacterial Infections Bacterial Infections and Mycoses Chemical and Drug Induced Liver Injury Chemically-Induced Disorders Digestive System Diseases Drug-Related Side Effects and Adverse Reactions Gram-Positive Bacterial Infections Infections Liver Diseases Mycobacterium Infections Poisoning Tuberculosis

Age range

16 year–85 year

Sex eligibility

All sexes

Study type

Observational

Primary location

Royal Infirmary Edinburgh

Edinburgh, EH16 4SA, United Kingdom

About this study

To improve patient stratification, the investigators have developed a panel of novel circulating liver specific and mechanistic biomarkers that report early acute liver injury. Such biomarkers are needed as current early biomarkers of liver injury lack sensitivity and specificity. The panel of biomarkers either have enhanced liver specificity or provide mechanistic insights. Currently, antituberculosis drug-induced liver injury (ATDILI) is the most frequent side-effect of anti-tuberculosis therapy and this hinders the effective treatment of TB, as it means that treatment regimens are not completed. At present, the risk of ATDILI means that monitoring of liver function is required, with levels of ALT measured monthly. If levels of ALT rise to 2-5x the upper limit of normal levels (ULN) and the patient is unwell the frequency of monitoring is increased to biweekly monitoring. Antibiotic therapy is only changed if levels of ALT remain greater than 3xULN, the patient continues to display symptoms and there is a positive causality assessment that the anti-tuberculosis drugs are causing ATDILI. This project will recruit patients taking antituberculosis drugs and determine the diagnostic and prognostic value of the biomarker panel, in relation to liver injury as a result of anti-tuberculosis therapy.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

Patients undergoing treatment for tuberculosis
Patients with the capacity to give consent

Exclusion criteria

Patients unable to give informed consent
Patients who refuse to take part
HIV positive patients

Treatment and study plan

Primary outcomes

Anti-tuberculosis drug-induced liver injury

Time frame: Upto 3 years, or until the end of TB treatment

Anti-tuberculosis drug-induced liver injury defined as ALT elevation more than three times the ULN in the presence of hepatitis symptoms and/or jaundice, or five times the ULN in the absence of symptoms.

This is a 'proof of concept' study to determine whether a panel of biomarkers are elevated in tuberculosis patients who develop anti-tuberculosis drug-induced liver injury.

Sponsors and collaborators

Lead sponsor

University of Edinburgh

Other

Collaborators

NHS Lothian

Registry information

Acronym: ALISTER

Important dates

Study start: 2017
Primary completion: 2020
Study completion: 2020
First posted: Jul 7, 2017
Registry last updated: May 21, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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Completed