Clinical trial NCT04124055: Saliva and Dried Blood Spot Therapeutic Drug Monitoring for MDR-TB in Tanzania
Official title: Saliva and Dried Blood Spot Therapeutic Drug Monitoring for MDR-TB in Tanzania
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: MDR-TB
Lead sponsor: University Medical Center Groningen
Sponsor class: OTHER
Collaborators: name: Kibong'oto Infectious Diseases Hospital
name: University of Virginia
First posted: 2019-10-11
Enrollment: 51
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Drug exposure
timeFrame: >2 weeks on treatment
Secondary outcomes:
Other outcomes:
Locations:
city: Kibong'oto
country: Tanzania
facility: Kibong'oto infectious diseases hospital
Study officials:
affiliation: Kibong'oto ID hospital
name: Stellah Mpagama, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.