Anti-TB therapy following drug-induced liver injury (TB-DILI)
| ISRCTN | ISRCTN92067975 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN92067975 |
| ClinicalTrials.gov (NCT) | Nil known |
| Clinical Trials Information System (CTIS) | 2020-004193-21 |
| Integrated Research Application System (IRAS) | 1005097 |
| Protocol serial number | 20RM006, IRAS 1005097 |
| Sponsor | Nottingham Clinical Trials Unit |
| Funder | National Institute for Health Research |
- Submission date
- 08/06/2022
- Registration date
- 25/08/2022
- Last edited
- 23/10/2025
- Recruitment status
- No longer recruiting
- Overall study status
- Ongoing
- Condition category
- Respiratory
Plain English summary of protocol
Background and study aims
The standard 4 drug treatment for active tuberculosis (TB) is very effective if the full 6-month course is completed. However, there can be side effects. An important side effect is drug-induced liver injury (DILI). Around 1 in 14 patients may be affected. For patients experiencing these complications, treatment is usually stopped for a time to allow their liver to recover. Once their liver has recovered treatment will need to be started again - ‘reintroduced’.
NICE TB guidelines recommend that all 4 drugs are reintroduced. The American Thoracic Society guidelines differ. These recommend that the drug pyrazinamide (Z) is left out, as it is thought to make DILI more likely. Although this three-drug treatment is still effective, it needs to be taken over nine months. This is more difficult for patients & more costly to the NHS. Currently, clinicians in the UK & globally choose between the two guidelines; some reintroduce Z whilst others do not.
This research will answer which of the 2 treatment options
a) leads to fewer patients experiencing DILI?
b) results in a better quality of life for patients?
c) offers better use of limited NHS resources?
Who can participate?
Adults who experience DILI whilst on standard TB treatment
What does the study involve?
The research will be conducted over 4 years across a number of hospital clinics in the UK and India. The research will include 350 adults who experience DILI whilst on standard TB treatment, with 90 enrolled for each year of the study. Patients will be selected at random to be in either one of two groups for the study. One group will have 4 drugs reintroduced (i.e. including Z). The other group will have only 3 drugs reintroduced, (i.e. excluding Z). Patients and clinicians will know which treatment they are getting. The trial primary outcome will be a laboratory-based measure of the number of patients that experience the return of DILI.
Patients medical records are checked for DILI recurrence and their quality of life will be measured using the EQ5D.
What are the possible benefits and risks of participating?
Benefits:
Not provided at time of registration
Risks:
The TB-DILI Trial is comparing two standards of care that are already widely in use across the UK, because of this we do not expect there to be any additional risks or disadvantages to taking part in the trial.
Where is the study run from?
Nottingham Clinical Trials Unit (UK)
When is the study starting and how long is it expected to run for?
June 2022 to May 2026
Who is funding the study?
National Institute for Health and Care Research (NIHR) (UK).
Who is the main contact?
Dr Wei Shen Lim, weishen.lim@nhs.net
Contact information
Scientific
Derby Road
Nottingham
NG7 2RD
United Kingdom
| Phone | +44 115 8231609 |
|---|---|
| TB-DILI@nottingham.ac.uk |
Principal investigator
Nottingham Clinical Trials Unit
Nottingham
NG5 1PB
United Kingdom
| Phone | +44 1159691169 |
|---|---|
| weishen.lim@nhs.net |
Study information
| Primary study design | Interventional |
|---|---|
| Study design | Interventional randomized controlled trial |
| Secondary study design | Randomised controlled trial |
| Study type | Participant information sheet |
| Scientific title | Reintroduction of anti-tuberculosis therapy following drug-induced liver injury: a randomised controlled trial (TB-DILI) |
| Study acronym | TB-DILI |
| Study objectives | The main purpose of the TB-DILI trial is to determine whether restarting TB treatment with only 3 drugs is safer for patients than restarting with 4 drugs. We will determine this by looking at how many patients on each treatment (restarted with 3 or 4 drugs) go on to experience a reoccurrence of DILI. The trial will also look at which of the treatment options is more cost-effective for the NHS. At the end of this trial, we hope to be able to advise the NHS on the best way that doctors should treat future TB-DILI patients. Patients will be asked to complete quality of life questionnaires to look at the impact quality of life in the different treatment options. |
| Ethics approval(s) |
Approved 03/08/2023, Tyne and Wear South REC (HRA Jarrow Room 001 Jarrow Business Centre Rolling Mill Road, Jarrow, NE32 3DT, United Kingdom; +44 207 1048282; tyneandwearsouth.rec@hra.nhs.uk), ref: 22/NE/0111 |
| Health condition(s) or problem(s) studied | Drug induced liver injury in patients receiving tuberculosis treatment. |
| Intervention | Eligible patients will be individually randomised on a 1:1 ratio to one of the treatment groups using an online randomisation system developed and maintained by the NCTU. Intervention Sequential full-dose reintroduction of a non-Z-containing 3-drug ATT regimen comprising ethambutol, isoniazid and rifampicin (EHR), as recommended by the American Thoracic Society (ATS) TB guideline. Treatment duration is 9 months, patients are followed up post 12 months randomisation. Control Sequential full-dose reintroduction of a Z-containing 4-drug ATT regimen comprising ethambutol, isoniazid, rifampicin and pyrazinamide (EHRZ), as recommended by the National Institute for Health and Care Excellence (NICE) TB guideline. Treatment duration is 6 months, patients are followed up post 12 months randomisation. Patients will have a telephone follow-up at 9 months. |
| Intervention type | Drug |
| Phase | Phase IV |
| Drug / device / biological / vaccine name(s) | Ethambutol, isoniazid, rifampicin, zinamide |
| Primary outcome measure(s) |
DILI recurrence within 12 months following randomisation. DILI recurrence could occur at any timepoint during the treatment period. Sites will perform routine clinical assessments to determine a DILI this data will then be submitted for adjudication. |
| Key secondary outcome measure(s) |
1. Severity of DILI recurrence measured using routine clinical assessments at 12 months |
| Completion date | 13/05/2026 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | All |
| Target sample size at registration | 350 |
| Key inclusion criteria | 1. Aged ≥18 years 2. Experienced DILI with standard 4-drug ATT for active pulmonary or extra-pulmonary TB 3. Medically suitable 4. for re-introduction of standard 4-drug ATT |
| Key exclusion criteria | 1. Requirement for alternative ATT 2. Unable to provide written informed consent |
| Date of first enrolment | 01/08/2022 |
| Date of final enrolment | 13/05/2025 |
Locations
Countries of recruitment
- United Kingdom
- India
Study participating centre
-
India
Results and Publications
| Individual participant data (IPD) Intention to share | No |
|---|---|
| IPD sharing plan summary | Data sharing statement to be made available at a later date |
| IPD sharing plan | The current data sharing plans for this study are unknown and will be available at a later date |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| HRA research summary | 28/06/2023 | No | No | ||
| Participant information sheet | Participant information sheet | 11/11/2025 | 11/11/2025 | No | Yes |
| Study website | Study website | 11/11/2025 | 11/11/2025 | No | Yes |
Editorial Notes
23/10/2025: The following changes were made to the trial record:
1. Contact details updated.
2. India was added to countries of recruitment.
3. The plain English summary was updated to reflect these changes.
03/09/2025: The following changes were made to the trial record:
1. The date of final enrolment was changed from 30/06/2026 to 13/05/2025.
2. The completion date was changed from 31/12/2026 to 13/05/2026.
20/01/2025: The contact email was updated.
03/11/2023: The following changes were made to the trial record:
1. The ethics approval was added.
2. The study website was added.
3. The participant information sheet was added.
4. The recruitment start date was changed from 31/05/2022 to 01/08/2022.
08/06/2022: Trial's existence confirmed by NHS HRA.
