Assessing Antibiotic Induced Liver Injury for Stratification of Tuberculosis Patients

Tuberculosis Clinical Trial

— ALISTER  

Official title:

Assessing Antibiotic Induced Liver Injury for Stratification of Tuberculosis Patients

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03211208
• Other study ID #: AC16145
• Status: Recruiting
• Start date: May 22, 2017
• Est. completion date: April 2020

Study information

• Verified date: October 2018
• Source: University of Edinburgh
• Contact: James Dear, Dr
• Phone: +44(0) 131 242 9214
• Email: james.dear[@]ed.ac.uk
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 540
• Est. completion date: April 2020
• Est. primary completion date: April 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 16 Years to 85 Years

Eligibility

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

Related Conditions & MeSH terms

• Anti-Tuberculous Drug Reaction
• Chemical and Drug Induced Liver Injury
• Drug-Induced Liver Injury
• Drug-Related Side Effects and Adverse Reactions
• Tuberculosis
• Wounds and Injuries

Locations

Country	Name	City	State
United Kingdom	Royal Infirmary Edinburgh	Edinburgh

Sponsors (2)

Lead Sponsor	Collaborator
University of Edinburgh	NHS Lothian

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Anti-tuberculosis drug-induced liver injury	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.	Upto 3 years, or until the end of TB treatment