DIAgnostics for Multidrug Resistant Tuberculosis in Africa (DIAMA)
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|ClinicalTrials.gov Identifier: NCT03303963|
Recruitment Status : Active, not recruiting
First Posted : October 6, 2017
Last Update Posted : August 3, 2022
|Condition or disease||Intervention/treatment|
|Tuberculosis, Multidrug-Resistant||Diagnostic Test: Deeplex test, MolBio TrueNat for 2nd line, GeneXpert 2nd line Diagnostic Test: Fluorescein DiAcetate (FDA) Microscopy,GeneXpert Ct value, pre-rRNA synthesis|
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 DST, the reference method for detecting resistance to 1st and 2nd line drugs. In addition, since Whole Genome Sequencing is the "reference" of molecular tests, Deeplex assay will also be validated again this test. In a second phase, Cepheid 2nd line Xpert and Molbio Truenat test, two 'lower tech' tests at the last stages of laboratory validations, will also be validated. The Cepheid Xpert 2nd line cartridge can be implemented in existing Xpert machines used for the Xpert MTB/Rif assays. These tests will be compared versus the Deeplex assay and versus WGS
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 WHO recommended monthly cultures: serial sputum samples will have Fluorescein DiAcetate (FDA) vital stain microscopy, measurement of the bacterial load using the Xpert MTB/Rif as well as precursor of ribosomal RNA measurement (pre-rRNA).
Together, these advances are expected to dramatically improve the currently dismal prognosis of MDR-TB in health systems in resource-poor settings.
|Study Type :||Observational|
|Estimated Enrollment :||2840 participants|
|Official Title:||Culture Free Diagnosis and Follow-up of Multidrug Resistant Tuberculosis Patients|
|Actual Study Start Date :||May 4, 2017|
|Actual Primary Completion Date :||June 30, 2022|
|Estimated Study Completion Date :||November 30, 2022|
Rifampicin resistant and susceptible patients
Study 1: Patients detected positive by the GeneXpert Mycobacterium tuberculosis/Rifampicin (susceptible and resistant to rifampicin)
Diagnostic Test: Deeplex test, MolBio TrueNat for 2nd line, GeneXpert 2nd line
Improvement of the diagnosis of Multi Drug Resistant-Tuberculosis patients with culture-free approaches. We have planned to diagnose Tuberculosis resistance to 1st and 2nd line drugs through novel molecular multiplex assays (Study 1) by:
Rifampicin resistant patients
Study 2: Follow up of the rifampicin resistant patients included in the study 1 during their treatment
Diagnostic Test: Fluorescein DiAcetate (FDA) Microscopy,GeneXpert Ct value, pre-rRNA synthesis
Improvement of the management of Multi Drug Resistant-Tuberculosis patients with culture-free approaches. We have planned to set up alternative culture-free approaches for the monitoring of patients' response to Multi Drug Resistant-Tuberculosis treatment (Study 2), with:
- Validation of Deeplex test [ Time Frame: 4 years ]Concordance between phenotypic Drug Susceptibility Test, WGS and Deeplex results
- Validation of GeneXpert 2nd line [ Time Frame: 4 years ]Concordance between WGS, Deeplex results and GeneXpert 2nd line results
- Validation of MolBio TrueNat for INH, FQ and BDQ [ Time Frame: 4 years ]Concordance between WGS, Deeplex results and MolBioTrueNat results
- Validation of FDA microscopy [ Time Frame: 4 years ]Concordance between Culture results and FDA microscopy results
- Validation of GeneXpert Ct value [ Time Frame: 4 years ]Concordance between Culture results and GeneXpert Ct value results
- Estimation of proportion of additional resistance in patients resistant to Rifampicin [ Time Frame: 4 years ]Evaluation to be done with the Deeplex test
- Measurement of the association of specific mutations against some drugs with programmatic treatment outcome [ Time Frame: 4 years ]Evaluation to be done with the Deeplex test
- Evaluation of the add value of Connectivity system in the management of Multi Drug Resistant-Tuberculosis patients [ Time Frame: 2 years ]Evaluation to be done with Data2Care connectivity system
Biospecimen Retention: Samples With DNA
At the enrolment, three samples (spot-overnight-spot) will be collected for the comparison of phenotypic results against molecular results.
During the treatment, two monthly samples (overnight-spot) will be collected for the comparison of culture result against FDA Microscopy and GeneXpert Ct values.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03303963
|Institute of Tropical Medecine|
|Centre National Hospitalier Universitaire de Pneumo-Phtisiologie de Cotonou|
|Cotonou, Atlantique/Littoral, Benin, 01BP321|
|The Tuberculosis Reference Laboratory Bamenda|
|Congo, The Democratic Republic of the|
|Institut National de Recherche Biomédicale (INRB)|
|Kinshasa, Congo, The Democratic Republic of the|
|Service de Pneumophtisiologie, Hôpital Ignace Deen, Conakry|
|Université des Sciences, des Techniques et des Technologies de Bamako, SEREFO|
|Rwanda Biomedical Center (RBC)|
|Université Cheick Anta Diop (UCAD)|
|Principal Investigator:||Dissou AFFOLABI, MD, MSc, PhD||Laboratoire de Référence des Mycobactéries|