Completion and Acceptability of Treatment Across Primary Care and the commUnity for Latent Tuberculosis

Study Overview
=================
Brief Summary
-----------------
This study investigates whether recent migrants to the United Kingdom are more likely to complete treatment for Latent Tuberculosis Infection (LTBI) if they are treated in the community (by General Practitioners/Family Doctors and pharmacists) than in a hospital TB clinic.

Detailed Description
-----------------
People with dormant/latent TB (LTBI) have TB bacteria in their bodies, but do not have any symptoms because the bacteria are not active. The investigators know that recent migrants with LTBI from countries where TB is very common (incidence greater than 150 per 100 000) are at risk of developing active TB (their dormant bacteria become active) after they arrive in the UK. Active TB can be both infectious and deadly. The treatment for LTBI is three-month course of antibiotics. This significantly reduces the risk of developing active TB. This treatment is currently arranged and supervised by hospital clinics, however, many migrants do not attend and numbers of people completing antibiotics is low. This leaves many at risk of developing active TB. This study investigates whether a community (primary care) based approach to the treatment of LTBI, coordinated by general practices and local pharmacists, will achieve higher rates of antibiotic completion. The London Borough of Newham, in the UK, has amongst the highest rates of active TB in Western Europe. As part of a strategy to tackle this disease burden, an innovative model of care has been implemented in the borough in which GPs and pharmacists screen and treat migrants with LTBI. Our trial will evaluate whether primary care based management of LTBI leads to higher rates of treatment completion amongst recent migrants when compared to hospital based care. This approach would save money (both for the health service and for patients in terms of travels costs) and reduce numbers of new cases of active TB. The treatment for Latent Tuberculosis Infection will be 3 months of combined oral Rifampicin and Isoniazid with Pyridoxine. The dosage is weight dependent.

Official Title
-----------------
Can Latent Tuberculosis Infection (LTBI) in Recent Migrants be Treated Effectively and Safely in Primary Care? A Cluster Randomised Controlled Trial.

Conditions
-----------------
Latent Tuberculosis

Intervention / Treatment
-----------------
* Other: Community/Primary Care
* Other: Hospital/TB Clinic


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients with LTBI aged 16-35 and who have entered the UK less than 5 years ago from a country with a TB incidence of greater than 150/100,000. Latent Tuberculosis is defined as a positive IGRA test without any symptoms or physical signs of active Tuberculosis and no evidence of active Tuberculosis on Chest X-ray. Exclusion Criteria: Pregnant or breastfeeding women Patients requiring medications that cannot be safely taken with Rifinah HIV infection. Individuals with known liver disease, or abnormal liver function tests (LFTs) Diagnosis of cirrhosis (jaundice, haematemesis, ascites or previous episodes of liver encephalopathy) Chronic or active hepatitis B or hepatitis C virus infection Previous treatment for TB or LTBI. Individuals who are unable to consent or who would usually be offered LTBI treatment under DOT because of their mental or social disabilities or those with drug or alcohol abuse Evidence of active TB

Ages Eligible for Study
-----------------
Minimum Age: 16 Years
Maximum Age: 35 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Health Services Research
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Cluster-randomised trial evaluating treatment completion (the primary outcome), uptake, acceptability, safety and cost-effectiveness of treating latent tuberculosis infection (LTBI) in migrants in primary care, compared with secondary care.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention<br>Participants with LTBI will be treated in the Community/Primary Care. | Other: Community/Primary Care<br>* The treatment of Latent Tuberculosis Infection (LTBI) in the community by General Practitioners (Family Doctors) and Pharmacists<br>|
| Active Comparator: Control<br>Participants with LTBI will be treated in the Hospital/TB Clinic | Other: Hospital/TB Clinic<br>* The treatment of Latent Tuberculosis Infection (LTBI) in the Hospital TB Clinic by specialist doctors and nurses<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Completion of Latent Tuberculosis Treatment | Based on patients taking at least 90 percent of doses of Rifinah during 3 months of treatment. | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete of Latent Tuberculosis Treatment | Based on patients taking at least 80 or 85 percent of doses during 3 months of treatment. | 3 months | 
| Adherence to Treatment | To describe the proportion of individuals in the two treatment arms who adhere to LTBI treatment based on the five-point MARS5 (Medication Adherence Report Scale) questionairre, collection of prescriptions and a point of care urine testing for metabolites of isoniazid (Iso-screen) performed at monthly intervals. | 3 months | 
| Acceptability of Treatment | To describe the proportion of individuals in the two treatment arms who accept LTBI treatment. This is defined as those initiating treatment and attending TB clinics and community pharmacies on at least one occasion. | 3 months | 
| Adverse Effects of Treatment | To assess the incidence of adverse effects of treatment for LTBI, including adverse liver function tests or any other effects leading to cessation of treatment. This will be assessed using liver function test results, and a monthly questionnaire. | 3 months | 
| Active Tuberculosis | The incidence of active TB occurring within 2 years after enrolment. TB incidence in the intervention and control group will be compared and there will be a sub-analysis of examining those who did or did not accept or complete treatment. This will be performed through matching the study population with the national Enhanced TB Surveillance System, where information on all reported TB cases nationally are recorded. | 2 years | 
| Patient Satisfaction | Assessed using a standardised non-validated questionnaire (Likert scale) | 3 months | 
| Cost-effectiveness of Treatment | Assessed using a health economic model that includes locally and nationally agreed tariffs for latent tuberculosis treatment. | 2 years | 
| Patient Knowledge | The impact of patients knowledge about Latent Tuberculosis on treatment acceptance and completion will be assessed at baseline using a standardised non-validated questionnaire. | 3 months |