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

Not Applicable

Completed

• Conditions: MDR-TB
• Interventions: Diagnostic Test: Therapeutic drug monitoring (TDM)

• Registration Number: NCT04124055
• Lead Sponsor: Jan-Willem C Alffenaar

Brief Summary

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

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.

Study Timeline

• Study Start: 2019-09-24
• Study First Submitted: 2019-10-09
• Study First Submitted QC: 2019-10-10
• Study First Posted: 2019-10-11
• Primary Completion: 2019-12-15
• Study Completion: 2019-12-31
• Status Verified: 2020-10
• Last Update Submitted: 2020-10-28
• Last Update Posted: 2020-10-30

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 51

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Therapeutic drug monitoring (TDM)	Therapeutic drug monitoring (TDM)	Therapeutic drug monitoring (TDM) based on Saliva and Dried blood spot samples

Primary Outcome Measures

Name	Time	Method
Drug exposure	>2 weeks on treatment	Drug concentration (mgL)

Trial Locations

Locations (1)

Kibong'oto infectious diseases hospital; 🇹🇿 Kibong'oto, Tanzania