Saliva and Dried Blood Spot Therapeutic Drug Monitoring for MDR-TB in Tanzania

Study Overview
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Brief Summary
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Dried blood spot and saliva samples are collected during multidrug resistant tuberculosis (MDR-TB) treatment to measure the drug concentration of levofloxacin. Feasibility of both analytical procedures in a high burdened setting is explored.

Detailed Description
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Background: Measuring pharmacokinetic variability of anti-tuberculosis (TB) drugs and responding by dose correction will allow individualized treatment to improve microbiological response, curb acquired drug-resistance, protect and extend the efficacy of novel drugs rolled-out to endemic areas (pharmacovigilance), reduce toxicity to patients and lead to treatment duration shortening. Aims and Objectives: Implement Dried Blood Spot (DBS) collection for performance of high-performance liquid chromatography (HPLC) to optimize multidrug resistant TB (MDR-TB) treatment in Tanzania. Simultaneously, provide a proof-of-principle-demonstration that the developed saliva point of care drug assay for measurement of fluoroquinolone concentration works in a field setting. Methods: This will be a phase II prospective diagnostic study among patients from a national referral of MDR-TB in Tanzania. The investigators anticipate recruiting a minimum of 50 study participants to power for the primary aim. Subjects will have a minimum amount of blood and saliva collected for therapeutic drug monitoring and the investigational drug assays respectively. Expected results include agreement of saliva point-of-care and DBS for measurement of fluoroquinolone concentrations in HPLC. Other important findings related to field-testing include the best time for sample collection within the dosing interval and the algorithmic use of DBS and saliva, and clinical - demographic factors such as HIV coinfection, concomitant drugs, and diabetes mellitus that may influence the saliva drug assay results. Performance characteristics (sensitivity, specificity, negative and positive predictive values) of the saliva point-of care (PoC) and DBS will be calculated as a measurement of accuracy with reference to the gold standard.

Official Title
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Saliva and Dried Blood Spot Therapeutic Drug Monitoring for MDR-TB in Tanzania

Conditions
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MDR-TB

Intervention / Treatment
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* Diagnostic Test: Therapeutic drug monitoring (TDM)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participant is receiving care at Kibong'oto hospital Age of 18 years or above Exclusion Criteria: Pregnancy at any gestation Co-morbid conditions such as generalized severe ulcers, Kaposi sarcoma, Hemophilia Participants with medical conditions like malignancy, dementia or those who will be critically ill and unable to consent and provide DBS and Saliva. Patients with Karnofsky score less than 40% or moribund

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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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Therapeutic drug monitoring (TDM)<br>Therapeutic drug monitoring (TDM) based on Saliva and Dried blood spot samples | Diagnostic Test: Therapeutic drug monitoring (TDM)<br>* Saliva and dried blood spot samples are collected. Based on the measured drug concentration the dose can be adjusted<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Drug exposure | Drug concentration (mgL) | >2 weeks on treatment |