Improving the Management of Drug Resistant Tuberculosis in the UK

Study Overview
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Brief Summary
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The 'rising tide' of antimicrobial resistance is a source of concern across most infectious diseases. In the UK, for example, 6.8% of the  8,500 tuberculosis patients seen in 2012 were resistant to the cheap and effective first-line drug isoniazid. It is of great importance to prevent the loss of current anti-tuberculosis drugs and preventing the spread of resistance by treating such patients as well as possible. Currently, guidance on the best treatments for isoniazid resistant tuberculosis is inconsistent globally. Data from randomised controlled trials, the peak quality of evidence, is sparse. It is thus important that studies using pre-existing observational data are undertaken. The investigators aim to use data and samples collected from Public Health England and National Health Service hospitals to determine a) the best treatments for patients with isoniazid resistant tuberculosis disease (cohort study) and b) how different causes of drug resistance in the infecting bacteria influence a) (nested case-control study). Eligible participants will have had isoniazid resistant tuberculosis (without associated rifampicin resistance) in England between 2009 and 2013 and will have been notified to Public Health England. The study will be conducted at University College London, National Health Service hospitals and Public Health England and will last until December 2017. Patient hospital records and disease surveillance records will be accessed and cultured bacteria from previously stored samples sequenced.

Official Title
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Improving the Management of Drug Resistant Tuberculosis in the UK

Conditions
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Tuberculosis

Intervention / Treatment
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* Drug: Any treatment regimen
* Other: Bacterial mutation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Isoniazid resistant non-multidrug resistant tuberculosis patients. Notified to Public Health England's Enhanced Tuberculosis Surveillance System between 2009-2013. Adults aged 18 years and over. Patients not treated at private hospitals. Exclusion Criteria: Non-notified patients. Individuals where the site of disease required more than 12 months of treatment. Individuals diagnosed post-mortem.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| All participants<br> | Drug: Any treatment regimen<br>* Treatment regimen used to treat patient once isoniazid resistance known (exposure of interest for cohort study)<br>Other: Bacterial mutation<br>* Resistance, compensatory or other mutation in the infecting strain of Mycobacterium tuberculosis (exposure of interest for nested case-control study)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment outcome | Negative versus positive treatment outcomes attributable to the treatment regimen commenced once isoniazid resistance known. Taken from clinical records. Also used to define cases and controls for nested case-control study. | Up to 12 months after the start of treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Isoniazid, Drug Resistance