Tuberculosis, Multidrug-Resistant Clinical Trial
Official title:
Culture Free Diagnosis and Follow-up of Multidrug Resistant Tuberculosis Patients
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.
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. ;
Status | Clinical Trial | Phase | |
---|---|---|---|
Active, not recruiting |
NCT05871489 -
Strengthening Evidence on Optimal Multidrug-resistant Tuberculosis Treatment Regimens
|
||
Active, not recruiting |
NCT02715271 -
Study of TB Lesions Obtained in Therapeutical Surgery
|
||
Active, not recruiting |
NCT04179500 -
A Trial to Evaluate the Male Reproductive Safety of Pretomanid in Adult Male Participants With Drug Resistant Pulmonary Tuberculosis Volunteers
|
Phase 2 | |
Completed |
NCT03086486 -
Various Doses and Durations of Linezolid Plus Bedaquiline & Pretomanid in Participants With Drug Resistant Tuberculosis
|
Phase 3 | |
Completed |
NCT01201941 -
Operational Assessment of Laboratory Information System for MDR-TB in Lima, Peru
|
N/A | |
Not yet recruiting |
NCT06441006 -
Program for Rifampicin-Resistant Disease With Stratified Medicine for Tuberculosis
|
Phase 3 | |
Completed |
NCT02413931 -
Nosocomial Transmission of MDR-TB in Bucharest, Romania
|
||
Recruiting |
NCT05306223 -
A Study of an Oral Short-course Regimen Including Bedaquiline for the Treatment of Participants With Multidrug-resistant Tuberculosis in China
|
Phase 4 | |
Completed |
NCT02573350 -
A Trial to Evaluate Safety, Tolerability, and Efficacy of Orally Administered OPC-67683
|
Phase 2 | |
Completed |
NCT02597621 -
Biomarkers for Therapy Response in Drug-resistant Tuberculosis
|
||
Recruiting |
NCT05555303 -
Preventing Acquired Resistance: Strengthen TB Treatment by Adding Amikacin in the First Treatment Week of Multidrug-resistant Tuberculosis
|
Phase 2 | |
Recruiting |
NCT03828201 -
Efficacy and Tolerability of Bedaquiline, Delamanid, Levofloxacin, Linezolid, and Clofazimine to Treat MDR-TB
|
Phase 2 | |
Recruiting |
NCT01212003 -
Training Protocol on the Natural History of Tuberculosis
|
||
Terminated |
NCT03237182 -
The Individualized M(X) Drug-resistant TB Treatment Strategy Study
|
Phase 4 | |
Completed |
NCT03338621 -
Trial to Evaluate the Efficacy, Safety and Tolerability of BPaMZ in Drug-Sensitive (DS-TB) Adult Patients and Drug-Resistant (DR-TB) Adult Patients
|
Phase 2/Phase 3 | |
Not yet recruiting |
NCT05007795 -
Test to Treat TB: Impact of Sputum Sequencing-guided Individualised Therapy on Outcomes in Drug-resistant Tuberculosis
|
N/A | |
Completed |
NCT03728725 -
Xpert MTB/XDR Clinical Evaluation Trial
|
||
Completed |
NCT02589782 -
Pragmatic Clinical Trial for a More Effective Concise and Less Toxic MDR-TB Treatment Regimen(s)
|
Phase 2/Phase 3 | |
Recruiting |
NCT02619994 -
Treatment Shortening of MDR-TB Using Existing and New Drugs
|
Phase 2 | |
Completed |
NCT01918397 -
Efficacy and Safety of Levofloxacin for the Treatment of MDR-TB
|
Phase 2 |