Research to improve the detection and treatment of latent tuberculosis infection: Treatment

Recruitment & Eligibility

Status: Ongoing

Sex: All

Target Recruitment: 920

Inclusion Criteria

1. Aged > = 16 years to < = 65 at screening
2. LTBI diagnosis is defined on the basis of all of the following:
2.1. A positive result on an Interferon Gamma Release Assay (IGRA), Tuberculin Skin Test (TST) or C-Tb skin test and
2.2. Negative TB symptoms at screening and
2.3. No signs of active TB on a Chest X-ray
3. Eligible for LTBI treatment at TB clinics and national LTBI screening services based on NICE guidelines, which means having one or more of the following :
3.1. Recent infection (contact tracing);
3.2. New entrants at risk (i.e., those that immigrated < 5 years from countries with a high incidence of TB, which is defined as > = 40 cases/100,000 population); or
3.3. Individuals who are assessed in the TB clinic for latent TB testing, or have been referred for treatment following testing by specialities or departments within primary or secondary care settings
4. Agree to LTBI treatment
5. Willing and able to provide written informed consent

Exclusion Criteria

1. Patients weighing < 30 kg.
2. Need for medications that cannot be safely taken together with study drugs
3. Any medical condition deserving priority of treatment (such as: porphyria, malabsorption syndromes, Clostridium difficile-associated diarrhoea and other conditions)
4. History of sensitivity/intolerance to isoniazid or rifamycins
5. Individuals with documented liver disease, defined as:
5.1. LFT (ALT/AST/bilirubin) over three times upper limit of normal (ULN) at baseline. This reflects normal clinical practice. For patient participant safety, liver function tests are carried on a regular basis. One abnormal value prevents the patient from participating on the study.
5.2. Clinical diagnosis of cirrhosis (jaundice, hematemesis, ascites or previous episodes of liver encephalopathy),
5.3. HbsAg positive or HCV antibody positive and deemed ineligible for LTBI treatment by the clinician
6. Intending to move outside of the treatment locality within 20 weeks of starting treatment
7. Individuals who would usually be offered LTBI treatment under Directly Observed Therapy (DOT) as part of enhanced case management in complex cases such as those from under-served groups (such as people who are homeless, misuse substances, have been in prison or who are vulnerable migrants).
8. Use of another experimental investigational medicinal product that is likely to interfere with the study medication within 3 months of study enrolment.
9. Women who are breastfeeding, pregnant, or of childbearing potential* who do not agree to use an effective method of contraception from the time consent is signed until 4 weeks after treatment discontinuation or completion.
10. Women of childbearing potential without a negative urine pregnancy test within 7 days prior to being registered for trial treatment.

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Adequate treatment adherence is defined as taking =90% of allotted doses within the allowable time frame specified by the treatment plan. Time-frames differ depending on the treatment arm that a participant is randomized to. 3HR and 3HP arms (i.e. arms 1, 2, 3, 4) have 16 weeks to complete, and the 1HP arm (i.e. arm 5) has 8 weeks to complete. Adherence data is checked at all follow-up visits.

Secondary Outcome Measures

Name	Time	Method

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