Drug-Induced Liver InjuryALISTERNCT03211208
Assessing Antibiotic Induced Liver Injury for Stratification of Tuberculosis Patients
An observational study of Drug-Induced Liver Injury and Anti-Tuberculous Drug Reaction, run by University of Edinburgh at 1 site in United Kingdom.
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. Read more about this study
- Who is it for?
- Ages 16 to 85 years
- Conditions the study is for
- Drug-Induced Liver Injury, Anti-Tuberculous Drug Reaction, Tuberculosis
- How many people
- 194 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 22 May 2017to 22 Mar 2020
- 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 16 to 85 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: Tuberculosis patients being treated at the outpatient clinic at the Royal Infirmary Edinburgh
Who may be able to join
- Patients undergoing treatment for tuberculosis
- Patients with the capacity to give consent
Who cannot join
- Patients unable to give informed consent
- Patients who refuse to take part
- HIV positive patients
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the detailed 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.
- Medical subject headings
- Chemical and Drug Induced Liver Injury, Tuberculosis
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Upto 3 years, or until the end of TB treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jul 2017
- Study start22 May 2017
- Primary completion22 Mar 2020
- Study completion22 Mar 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Drug-Induced Liver InjuryStudies of the same condition, open and under way.
- More trials run by University of EdinburghThe sponsor's other registered studies.
- 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
- Case-control
- Time perspective
- Prospective
- Enrolment
- 194 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Edinburgh
- Sponsor type
- University, hospital or other
- Collaborators
- NHS Lothian
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03211208
- Sponsor's protocol ID
- AC16145
- Acronym
- ALISTER
- Status last verified
- May 2024
- First submitted
- 26 May 2017
- Last updated
- 21 May 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Rupprechter SAE, Sloan DJ, Oosthuyzen W, Bachmann TT, Hill AT, Dhaliwal K, Templeton K, Matovu J, Sekaggya-Wiltshire C, Dear JW. MicroRNA-122 and cytokeratin-18 have potential as a biomarkers of drug-induced liver injury in European and African patients on treatment for mycobacterial infection. Br J Clin Pharmacol. 2021 Aug;87(8):3206-3217. doi: 10.1111/bcp.14736. Epub 2021 Jan 26.
PubMed 33432705
Study at a glance
From the registry record, last updated by the sponsor on 21 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Assessing Antibiotic Induced Liver Injury for Stratification of Tuberculosis Patients
- ClinicalTrials.gov ID
- NCT03211208
- Acronym / sponsor ID
- ALISTER / AC16145
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 194 participants (actual)
- Lead sponsor
- University of EdinburghUniversity, hospital or other
- Collaborators
- NHS Lothian
- Study start
- 22 May 2017 (actual)
- Primary completion
- 22 Mar 2020 (actual)
- Study completion
- 22 Mar 2020 (actual)
- First posted
- 7 Jul 2017 (actual)
- 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.
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.
Detailed 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.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
Who may qualify
- Ages
- 16 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Tuberculosis patients being treated at the outpatient clinic at the Royal Infirmary Edinburgh
Key inclusion criteria (2 listed)
- Patients undergoing treatment for tuberculosis
- Patients with the capacity to give consent
Key exclusion criteria (3 listed)
- Patients unable to give informed consent
- Patients who refuse to take part
- HIV positive patients
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
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.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 May 2024.
- Derived from this study: PubMed 33432705Rupprechter SAE, Sloan DJ, Oosthuyzen W, Bachmann TT, Hill AT, Dhaliwal K, Templeton K, Matovu J, Sekaggya-Wiltshire C, Dear JW. MicroRNA-122 and cytokeratin-18 have potential as a biomarkers of drug-induced liver injury in European and African patients on treatment for mycobacterial infection. Br J Clin Pharmacol. 2021 Aug;87(8):3206-3217. doi: 10.1111/bcp.14736. Epub 2021 Jan 26.
- Individual participant dataSharing planned: No
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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.
The record lists no contact. Use the official record to reach the sponsor.
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 Drug-Induced Liver Injury and Anti-Tuberculous Drug Reaction, run by University of Edinburgh 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 2 inclusion and 3 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: finished, as of the sponsor's last update on 21 May 2024. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Anti-tuberculosis drug-induced liver injury (time frame: Upto 3 years, or until the end of TB treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03211208, which also lists 1 linked publication.
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 21 May 2024.