• In the UK, TB (tuberculosis) is routinely treated with a combination of four medicines, this is referred to as 4-drug treatment. Most patients can successfully complete their treatment course without any problems. Unfortunately, in some cases, the treatment can begin to cause damage to the liver, this is called drug-induced liver injury (DILI). To protect the liver and encourage it to recover the TB treatment is stopped.

• Once the liver has recovered doctors must decide how to restart TB treatment. There are two options that are used in the NHS. One is to re-introduce all 4 drugs again and complete 6 months of treatment, the other option is to re-introduce only 3 drugs, leaving out the drug pyrazinamide (Z), and complete 9 months of treatment. 

• Some research suggests that leaving out Z lowers the chance that a patient will experience another episode of DILI and might be safer for the patient and less disruptive to their TB treatment. The main aim of the study is to find out the safest and most effective way to treat the patient; the study information will also be used to see how benefits to the NHS can possibly be implemented.

• The main purpose of the TB-DILI study is to determine whether restarting TB treatment with only 3 drugs is safer for patients than 4 drug. We will determine this by looking at how many patients on each treatment strategy experience another bout of DILI.
• Participants on the study will be randomly assigned one of the two treatment options. We will also perform an investigation to see which strategy is more cost-effective for the NHS. At the end of this study, we hope to be able to advise the NHS on which strategy doctors should use for future TB-DILI patients.

• If you decide to help with this research, you will be asked to sign a consent form. Once that form is completed the medical information relating to your liver injury and TB treatment will be sent to one of the research team liver specialists to confirm the diagnosis of DILI, they will have a maximum of 5 days to confirm that the DILI is related to your TB treatment.

• After the DILI is confirmed as being related to your TB treatment you will be asked to fill in a short questionnaire about your health and wellbeing that takes a few minutes to complete.  

• If the liver specialists do not find that your DILI is related to your TB treatment based on a specified criteria for the TB-DILI study, then you will not be eligible to participate in the trial. Your care will not be affected, and you doctor will manage your care as they see clinically appropriate.

• You will be asked to complete this questionnaire at several points over the next year. These timepoints are shown in the flow chart at the end of this section. You might be asked to fill in this questionnaire in person where you are receiving your TB treatment, over the phone with a member of the study team, or online/via post by yourself.

• Your doctor will manage your care as usual as you recover from the DILI. Once your liver has recovered and you have completed the questionnaire again the treatment you will receive will be decided by a process called randomisation. Neither you, nor your doctor or nurse will be able to choose: a computer programme will allocate you to the 3-drug group or the 4-drug group. This may sound strange, but randomisation ensures a fair comparison. The computer programme puts equal numbers of patients of different ages and states of health in each group so that at the end of the study we are sure that any differences between people in the two groups are due to whether had the 3-drug or 4-drug treatment, rather than anything else.

• Your doctor will continue to manage your care as usual in the NHS and provide information on your health to the study team. This study does not require you to attend any additional visits than you would normally attend for TB treatment.

• The study team will monitor your treatment and recovery for 12 months after you have been assigned to a treatment. During that time, we may contact you by phone, e-mail or post to update you on the study, remind you to complete the questionnaires or to collect data about how you have been feeling since your last contact with them.

•  With your permission, we will inform your GP about your participation in this trial.

• Taking part in the trial may not directly benefit you, but the information we collect from this trial will help the NHS to determine which treatment is less likely to cause drug related liver injury (DILI) recurring in TB patient groups. It will inform national and international clinical guidelines and as a result, influence clinical practice.

• 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 you taking part in the trial.

• Researchers at the Nottingham Clinical Trials Unit (part of the University of Nottingham) will need to use information from you, your medical records, and your TB care team for this research project. All information about you will be kept safe and secure. 

• This information will include your initials, NHS number, name and contact details.  The researchers will use this information to do the research or to check your records to make sure that the research is being done properly. People who do not need to know who you are will not be able to see your name or contact details, your data will have a unique code number instead. 

• Once the trial has finished, some of the data will be kept so the results can be checked and you can be told what happened in the study. Reports will be written in a way so that no-one can work out that you took part in the trial.  

• You can stop being part of the trial at any time, without giving a reason, but we will keep information about you that we already have. If you choose to stop taking part in the trial, we would like to continue collecting information about your health from central NHS records. If you do not want this to happen, tell us and we will stop.
• We need to manage your records in specific ways for the research to be reliable. This means that we won’t be able to let you see or change the data we hold about you. 
• After 15 years your data collected during the study will be disposed of securely. If you give us your permission, we may keep your contact details so we can get in touch if there is any relevant future research that you may be interested in taking part in. You will also have the option to take part in future research using your data saved from this study. If you do not wish for your contact details to be kept to be contacted about future research, these will also be disposed of securely at the end of the trial.

You can find out more about how we use your information:

• at www.hra.nhs.uk/information-about-patients/ and www.hra.nhs.uk/patientdataandresearch
• at <sponsor privacy notice website address>
• by asking one of the research team
• by sending an email to TB-DILI@nottingham.ac.uk

• This trial should conclude 12 months after your randomisation when you have completed the final questionnaire. If this is not the case your treatment will continue as decided by your usual care team. If you withdraw from the trial, we will need to keep and use the data collected up to your withdrawal. At the end of the trial the results will be published in scientific medical journals and presented at conferences. You will not be identified in any publication. We will send you a newsletter with a summary of the trial findings.