Ignite Creation Date:
2024-05-06 @ 10:22 AM
Last Modification Date:
2024-10-26 @ 12:29 PM
Study NCT ID:
NCT03237182
Status:
TERMINATED
Last Update Posted:
2023-09-01
First Post:
2017-07-27
Brief Title:
The Individualized MX Drug-resistant TB Treatment Strategy Study
Sponsor:
Centre for the AIDS Programme of Research in South Africa
Organization:
Centre for the AIDS Programme of Research in South Africa
Study Overview
Official Title:
The Individualized MX Drug-resistant TB Treatment Strategy Study A Strategy to Improve Treatment Outcomes in Patients With Drug-resistant TB
Status:
TERMINATED
Status Verified Date:
2023-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
WHO 2022 guidelines for DR-TB treatment are set to change These guidelines recommend the use of an all-oral short course BPAL regimenTherefore ongoing implementation of the study is considered futile
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
InDEX
Brief Summary:
This is a randomized controlled clinical trial comparing treatment success of a gene-derived individualized drug-resistant Tuberculosis regimen to a standard Tuberculosis regimen based on South African National Tuberculosis guidelines
Detailed Description:
When drug resistance is detected by molecular methods such as the Xpert MTBRIF assay second-line Multi Drug-Resistant MDR Tuberculosis treatment is started in the complete absence of detailed resistance information The diagnosis of Multi Drug-Resistant Tuberculosis is confirmed only on availability of Line Probe Assay LPADrug Susceptibility Testing DST results Extremely Drug-Resistant XDR Tuberculosis is diagnosed by in vitro phenotypic resistance to Rifampicin Isoniazid fluoroquinolones and injectable second-line drugs ie amikacin kanamycin or capreomycin Existing culture based Drug Susceptibility Testing provides results after 6-8 weeks This duration may be further increased by other existing laboratory challenges such as culture contamination
Furthermore initial regimens are often not optimal and sometimes completely ineffective as there is a lack of Drug Susceptibility Testing to support them More importantly even optimal regimens are changed due to patient intolerance of the drugs side effects
Whole Genome Sequencing WGS has the advantage of determining the complete Deoxyribonucleic acid DNA sequence of an organisms genome at a single time point Using this technology genotypic mutations conferring resistance to anti-tuberculosis drugs can be identified This information will assist in identifying not only potential resistant drugs but also susceptible drugs and thus enable a more accurate and appropriate choice of regimen In addition drugs that will not add value to the treatment outcome but will increase rates of adverse drug reactions can be eliminated earlier improving drug-resistant TB treatment outcomes
In this proposal we aim to use Mycobacterium Tuberculosis MTB whole genome sequencing prior to the selection of a drug-resistant tuberculosis treatment regimen and thus provide an individualized treatment strategy for drug-resistant tuberculosis By adopting this method we hope to improve culture negative survival rates at 6 months post treatment initiation
This study will include 448 adult patients age 18 years that meet inclusion criteria Patients referred by provincial satellite facilities with microbiological confirmation of drug-resistant tuberculosis eg Xpert MTBRIF assay Line Probe Assay to King DinuZulu Hospital KDH will be recruited Patients randomized to the control arm will receive standard of care SOC treatment Patients randomized to the intervention arm will be given an individualized treatment regimen based on whole genome sequencing conducted on Mycobacteria Growth Indicator Tube MGIT positive sputum samples collected at the screening visit
Furthermore initial regimens are often not optimal and sometimes completely ineffective as there is a lack of Drug Susceptibility Testing to support them More importantly even optimal regimens are changed due to patient intolerance of the drugs side effects
Whole Genome Sequencing WGS has the advantage of determining the complete Deoxyribonucleic acid DNA sequence of an organisms genome at a single time point Using this technology genotypic mutations conferring resistance to anti-tuberculosis drugs can be identified This information will assist in identifying not only potential resistant drugs but also susceptible drugs and thus enable a more accurate and appropriate choice of regimen In addition drugs that will not add value to the treatment outcome but will increase rates of adverse drug reactions can be eliminated earlier improving drug-resistant TB treatment outcomes
In this proposal we aim to use Mycobacterium Tuberculosis MTB whole genome sequencing prior to the selection of a drug-resistant tuberculosis treatment regimen and thus provide an individualized treatment strategy for drug-resistant tuberculosis By adopting this method we hope to improve culture negative survival rates at 6 months post treatment initiation
This study will include 448 adult patients age 18 years that meet inclusion criteria Patients referred by provincial satellite facilities with microbiological confirmation of drug-resistant tuberculosis eg Xpert MTBRIF assay Line Probe Assay to King DinuZulu Hospital KDH will be recruited Patients randomized to the control arm will receive standard of care SOC treatment Patients randomized to the intervention arm will be given an individualized treatment regimen based on whole genome sequencing conducted on Mycobacteria Growth Indicator Tube MGIT positive sputum samples collected at the screening visit
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None