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Clinical Trial Summary

Recent advances in molecular diagnostics of tuberculosis, especially the GeneXpert Mycobacterium tuberculosis/Rifampicin test have reduced the time to diagnose Rifampicin Resistant Tuberculosis (RR-TB) but only rifampicin resistance is diagnosed, leading to presumptive diagnosis of resistance to isoniazid and maybe other drugs. Thus in low and middle income countries, most drug sensitivity testing relies on phenotypic drug resistance testing, which takes up to 4 months. In addition, currently, culture on monthly sputum samples is recommended by the World Health Organization for follow-up of Rifampicin Resistant Tuberculosis patients under treatment. Unfortunately, culture is often not locally available and samples need to be transported from field to culture laboratories. The associated transport delays lead to high rates of contamination and false negative culture, particularly in laboratories in low resource settings. Many gaps for the diagnosis and management of RR-TB patients still need to be addressed and the DIAMA project (DIAgnostics for Multidrug resistant tuberculosis in Africa) study aims to address some of them.

Clinical Trial Description

The proposed DIAMA (DIAgnostics for Multidrug resistant tuberculosis in Africa) study aims to address current gaps in the diagnosis and management of patients with Multi-Drug-Resistant (MDR) tuberculosis. Building on existing networks and research collaborations previously funded by the European & Developing Countries Clinical Trials Partnership (EDCTP), this project involved partners in West, Central, and East Africa. It aims to evaluate and implement rapid and accurate molecular tests for several anti Tuberculosis drugs, to replace the current dependency on phenotypic drug resistance testing, which takes up to 4 months and is technically so demanding that few laboratories can perform it correctly.

The project builds on the continuous surveillance of Tuberculosis retreatment patients for rifampicin resistance. Two African partners (Benin and Rwanda) with advanced molecular laboratories are establishing reference laboratories for the 'Deeplex' assay, a novel multiplex deep sequencing-based drug resistance diagnostic platform that simultaneously provides sequence information of genes that confer resistance to several key anti tuberculosis drugs. Partners are recruiting all patients with rifampicin resistant Tuberculosis, and a subset of those with rifampicin sensitive Tuberculosis. In a first phase, sputum will be shipped for the Deeplex assay, for comparison against phenotypic Drug Susceptibility Testing (DST), the reference method for detecting resistance to 1st and 2nd line anti-Tuberculosis drugs. In a second phase, InSilixa and Cepheid 2nd line GeneXpert, two 'lower tech' tests at the last stages of laboratory validations, will be implemented in all countries that have established recruitment of retreatment patients. The InSilixa lab-on-chip assay, powered by a smartphone, is able to query 117 drug resistance conferring mutations at around $20 per test. The Cepheid GeneXpert 2nd line cartridge can be implemented in existing GeneXpert machines used for the GeneXpert Mycobacterium tuberculosis/Rifampicin (MTB/Rif) assays. These two tests will be compared versus the Deeplex assay.

Using the latest advances in DataTocare software developed by one of the project partners, molecular results will be communicated in real time to the National Tuberculosis Programmes, so that Multi Drug Resistant Tuberculosis patients can swiftly start appropriate treatment. The added-value of this system will be evaluated as a pilot study in some sites.

Lastly, once patients have initiated MDR treatment, they will be monitored for treatment success by faster alternative approaches to the World Health Organization recommended monthly cultures: serial sputum samples will have Fluorescein DiAcetate vital stain microscopy and measurement of the bacterial load using the GeneXpert MTB/Rif. Together, these advances are expected to dramatically improve the currently dismal prognosis of MDR patients in health systems in resource-poor settings. ;

Study Design

Related Conditions & MeSH terms

NCT number NCT03303963
Study type Observational
Source Laboratoire de Référence des Mycobactéries
Contact Dissou AFFOLABI, MD, MSc, PhD
Phone 66614862
Status Recruiting
Phase N/A
Start date May 4, 2017
Completion date May 31, 2021

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