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

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.

Study Overview

• Status: Completed
• Conditions: MDR-TB
• Intervention / Treatment: Diagnostic test: Therapeutic drug monitoring (TDM)

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 Type: Interventional
• Enrollment (Actual): 51
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Tanzania
  • Kibong'oto, Tanzania
    • Kibong'oto Infectious Diseases Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Therapeutic drug monitoring (TDM); Therapeutic drug monitoring (TDM) based on Saliva and Dried blood spot samples	Diagnostic test: Therapeutic drug monitoring (TDM); Saliva and dried blood spot samples are collected. Based on the measured drug concentration the dose can be adjusted

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Jan-Willem C Alffenaar
• Collaborators: University of Virginia; Kibong'oto Infectious Diseases Hospital
• Investigators: Principal Investigator: Stellah Mpagama, PhD, Kibong'oto ID hospital

Publications and helpful links

General Publications

• Mohamed S, Mvungi HC, Sariko M, Rao P, Mbelele P, Jongedijk EM, van Winkel CAJ, Touw DJ, Stroup S, Alffenaar JC, Mpagama S, Heysell SK. Levofloxacin pharmacokinetics in saliva as measured by a mobile microvolume UV spectrophotometer among people treated for rifampicin-resistant TB in Tanzania. J Antimicrob Chemother. 2021 May 12;76(6):1547-1552. doi: 10.1093/jac/dkab057.

Study record dates

Study Major Dates

• Study Start (Actual): September 24, 2019
• Primary Completion (Actual): December 15, 2019
• Study Completion (Actual): December 31, 2019

Study Registration Dates

• First Submitted: October 9, 2019
• First Submitted That Met QC Criteria: October 10, 2019
• First Posted (Actual): October 11, 2019

Study Record Updates

• Last Update Posted (Actual): October 30, 2020
• Last Update Submitted That Met QC Criteria: October 28, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Actinomycetales Infections; Mycobacterium Infections; Tuberculosis; Tuberculosis, Multidrug-Resistant
• Other Study ID Numbers: S-DBS-TDM-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No