Treatment of Latent Tuberculosis in Socially Marginalised Citizens

Study Overview
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Brief Summary
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An open-label, randomised controlled trial comparing compliance to treatment for latent tuberculosis infection in socially marginalised citizens. Participants will be randomized to either daily isoniazid for 6 months or weekly rifapentine and isoniazid as directly observed therapy for twelve weeks.

Detailed Description
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Eligible participants will be randomised to receive either daily isoniazid for 6 months with monthly visits for pill count, evaluation of adverse events and dispensing of isoniazid for the next month, or weekly doses of rifapentine and isoniazid for twelve weeks as direct observed therapy where the drugs are administered in the presence of a study nurse or doctor. Control bloodsamples (ALAT, alkaline phosphatase, bilirubin, INR, haemoglobin, trombocytes and leukocyte differential count) will be taken at baseline and at least once during treatment in the rifapentine and isoniazid group and at least twice in the isoniazid-only group. One year after treatment completion participants will be called in for evaluation for active tuberculosis.

Official Title
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A Randomised Controlled Trial of a 12-dose Rifapentine and Isoniazid (RPT+INH) Regimen Using Direct Observed Therapy (DOT) Versus 6 Months of Daily Isoniazid for Latent Tuberculosis Infection (LTBI) in Socially Marginalised People

Conditions
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Compliance, Patient

Intervention / Treatment
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* Drug: Rifapentine
* Drug: Isoniazid


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Reporting to be homeless (independent of whether the person has an official address) or regularly seeking homeless shelters or public institutions to supply basic needs LTBI defined by positive IGRA test Found plausible by study doctor that the person has been exposed to tuberculosis within 2 years Aged 18 years or older Exclusion Criteria: Previously treated for tuberculosis Pregnant or breastfeeding Active tuberculosis (evaluated by chest x-ray and examination by a trained doctor) Unable to give informed consent Tested positive for LTBI as part of contact investigation where the index case has or is suspected to have INH of RIF resistant TB Known HIV on antiretroviral treatment Porphyria Known allergy to rifamycins or isoniazid Known epilepsy Known liver disease causing affected liver parameters (ALAT, alkaline phosphatase, bilirubin, INR) Any lab abnormality, disease, concomitant medication or condition that, in the opinion of the investigator, excludes a person from participating

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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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: RPT-INH<br>Participants treated with weekly rifapentine and isoniazid for twelve weeks. | Drug: Rifapentine<br>* Treatment with weekly rifapentine and isoniazid as Directly Observed Therapy in 12 weeks<br>* Other names: isoniazid;Drug: Isoniazid<br>* Treatment with daily isoniazid in 6 months<br>|
| Active Comparator: control<br>Participants treated with daily isoniazid for six months | Drug: Isoniazid<br>* Treatment with daily isoniazid in 6 months<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| adherence | adherence to treatment in the two groups measured by counting number of pills taken in each group. | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| active tuberculosis | active tuberculosis within the study period. In case of suspected tuberculosis during the study the participant will be refered for examination by specialists. At 1 year follow-up participants will have a chest x-ray and physical examination by study doctor to screen for signs of active tuberculosis. If active tuberculosis is suspected further examinations will be performed by specialists. | 5 years | 
| adverse events | for both groups all adverse events will be recorded | 2 years |