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

Sponsor

Jan-Willem C Alffenaar (Other)

Overall Status

Completed

CT.gov ID

NCT04124055

Collaborator

kibong'oto Infectious diseases hospital (Other), University of Virginia (Other)

Enrollment

Location

Arm

3.2

Actual Duration (Months)

15.8

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
MDR-TB	Diagnostic Test: Therapeutic drug monitoring (TDM)	N/A

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 Design

Study Type:

Interventional

Actual Enrollment :

51 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Sep 24, 2019

Actual Primary Completion Date :

Dec 15, 2019

Actual Study Completion Date :

Dec 31, 2019

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Drug exposure [>2 weeks on treatment]
Drug concentration (mgL)

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Kibong'oto infectious diseases hospital	Kibong'oto		Tanzania

Sponsors and Collaborators

Jan-Willem C Alffenaar
kibong'oto Infectious diseases hospital
University of Virginia

Investigators

Principal Investigator: Stellah Mpagama, PhD, Kibong'oto ID hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Jan-Willem C Alffenaar, prof, University Medical Center Groningen

ClinicalTrials.gov Identifier:

NCT04124055

Other Study ID Numbers:

S-DBS-TDM-001

First Posted:

Oct 11, 2019

Last Update Posted:

Oct 30, 2020

Last Verified:

Oct 1, 2020

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Product Manufactured in and Exported from the U.S.:

Additional relevant MeSH terms:

Tuberculosis, Multidrug-Resistant

Study Results

No Results Posted as of Oct 30, 2020