- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03303963
DIAgnostics for Multidrug Resistant Tuberculosis in Africa (DIAMA)
Culture Free Diagnosis and Follow-up of Multidrug Resistant Tuberculosis Patients
Study Overview
Status
Conditions
Detailed 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 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
Enrollment (Actual)
Contacts and Locations
Study Locations
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Antwerp, Belgium
- Institute of Tropical Medecine
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Atlantique/Littoral
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Cotonou, Atlantique/Littoral, Benin, 01BP321
- Centre National Hospitalier Universitaire de Pneumo-Phtisiologie de Cotonou
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Bamenda, Cameroon
- The Tuberculosis Reference Laboratory Bamenda
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Kinshasa, Congo, The Democratic Republic of the
- Institut National de Recherche Biomédicale (INRB)
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Jīma, Ethiopia
- Jimma University
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Conakry, Guinea
- Service de Pneumophtisiologie, Hôpital Ignace Deen, Conakry
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Bamako, Mali
- Université des Sciences, des Techniques et des Technologies de Bamako, SEREFO
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Ibadan, Nigeria
- Damien Fundation
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Kigali, Rwanda
- Rwanda Biomedical Center (RBC)
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Dakar, Senegal
- Université Cheick Anta Diop (UCAD)
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Sampling Method
Study Population
Two multi center observational studies will be conducted:
Study 1: Cross sectional study for Tuberculosis(TB) cases aged ≥ 15 (all Rifampicin resistant (RR) ones (new cases or retreatment patients) and equal number of Rifampicin sensitive retreatment patients from the same country) with comparison of TB resistance diagnostic test performance at baseline. There are 2 phases in this project; phase 1 is the comparison of Deeplex results against the phenotypic results and WGS (Gold standard), phase 2 is the comparison of MolBio TrueNat and GeneXpert 2nd generation results against Deeplex and WGS (gold standard).
Study 2: Cohort study of RR-TB patients (recruited in Study 1) under treatment with comparison of the performance of FDA and GeneXpert compared to solid culture
Description
Inclusion criteria:
- Being ≥ 15 year old
- Having a positive test on GeneXpert (M. tuberculosis) with or without resistance detected to rifampicin
- Willing and able to provide written informed consent, or for minors: assent from and consent from a legal representative
Exclusion Criteria: None
Study Plan
How is the study designed?
Design Details
- Observational Models: Cohort
- Time Perspectives: Prospective
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
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Rifampicin resistant and susceptible patients
Study 1: Patients detected positive by the GeneXpert Mycobacterium tuberculosis/Rifampicin (susceptible and resistant to rifampicin)
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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:
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Rifampicin resistant patients
Study 2: Follow up of the rifampicin resistant patients included in the study 1 during their treatment
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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:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Validation of Deeplex test
Time Frame: 4 years
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Concordance between phenotypic Drug Susceptibility Test, WGS and Deeplex results
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4 years
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Validation of GeneXpert 2nd line
Time Frame: 4 years
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Concordance between WGS, Deeplex results and GeneXpert 2nd line results
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4 years
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Validation of MolBio TrueNat for INH, FQ and BDQ
Time Frame: 4 years
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Concordance between WGS, Deeplex results and MolBioTrueNat results
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4 years
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Validation of FDA microscopy
Time Frame: 4 years
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Concordance between Culture results and FDA microscopy results
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4 years
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Validation of GeneXpert Ct value
Time Frame: 4 years
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Concordance between Culture results and GeneXpert Ct value results
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4 years
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Estimation of proportion of additional resistance in patients resistant to Rifampicin
Time Frame: 4 years
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Evaluation to be done with the Deeplex test
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4 years
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Measurement of the association of specific mutations against some drugs with programmatic treatment outcome
Time Frame: 4 years
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Evaluation to be done with the Deeplex test
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4 years
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Evaluation of the add value of Connectivity system in the management of Multi Drug Resistant-Tuberculosis patients
Time Frame: 2 years
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Evaluation to be done with Data2Care connectivity system
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2 years
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Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Dissou AFFOLABI, MD, MSc, PhD, Laboratoire de Référence des Mycobactéries
Publications and helpful links
General Publications
- Boehme CC, Nabeta P, Hillemann D, Nicol MP, Shenai S, Krapp F, Allen J, Tahirli R, Blakemore R, Rustomjee R, Milovic A, Jones M, O'Brien SM, Persing DH, Ruesch-Gerdes S, Gotuzzo E, Rodrigues C, Alland D, Perkins MD. Rapid molecular detection of tuberculosis and rifampin resistance. N Engl J Med. 2010 Sep 9;363(11):1005-15. doi: 10.1056/NEJMoa0907847. Epub 2010 Sep 1.
- Bastos ML, Hussain H, Weyer K, Garcia-Garcia L, Leimane V, Leung CC, Narita M, Pena JM, Ponce-de-Leon A, Seung KJ, Shean K, Sifuentes-Osornio J, Van der Walt M, Van der Werf TS, Yew WW, Menzies D; Collaborative Group for Meta-analysis of Individual Patient Data in MDR-TB. Treatment outcomes of patients with multidrug-resistant and extensively drug-resistant tuberculosis according to drug susceptibility testing to first- and second-line drugs: an individual patient data meta-analysis. Clin Infect Dis. 2014 Nov 15;59(10):1364-74. doi: 10.1093/cid/ciu619. Epub 2014 Aug 5.
- Aung KJ, Van Deun A, Declercq E, Sarker MR, Das PK, Hossain MA, Rieder HL. Successful '9-month Bangladesh regimen' for multidrug-resistant tuberculosis among over 500 consecutive patients. Int J Tuberc Lung Dis. 2014 Oct;18(10):1180-7. doi: 10.5588/ijtld.14.0100.
- Piubello A, Harouna SH, Souleymane MB, Boukary I, Morou S, Daouda M, Hanki Y, Van Deun A. High cure rate with standardised short-course multidrug-resistant tuberculosis treatment in Niger: no relapses. Int J Tuberc Lung Dis. 2014 Oct;18(10):1188-94. doi: 10.5588/ijtld.13.0075.
- Van Deun A, Maug AK, Salim MA, Das PK, Sarker MR, Daru P, Rieder HL. Short, highly effective, and inexpensive standardized treatment of multidrug-resistant tuberculosis. Am J Respir Crit Care Med. 2010 Sep 1;182(5):684-92. doi: 10.1164/rccm.201001-0077OC. Epub 2010 May 4.
- Pillay S, Steingart KR, Davies GR, Chaplin M, De Vos M, Schumacher SG, Warren R, Theron G. Xpert MTB/XDR for detection of pulmonary tuberculosis and resistance to isoniazid, fluoroquinolones, ethionamide, and amikacin. Cochrane Database Syst Rev. 2022 May 18;5(5):CD014841. doi: 10.1002/14651858.CD014841.pub2.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- DRIA2014-326
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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