The Individualized M(X) Drug-resistant TB Treatment Strategy Study

NCT03237182 | Terminated Phase 4 DMC

• 1 other identifier: CAP 020
• Study Type: interventional
• Target: 205
• Locations: 1 country
• Sites: 1

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.

Conditions

Tuberculosis, Multidrug-Resistant

Keywords

whole genome sequencing;

Outcome Measures

Primary Outcomes (2)

• Culture negative survival rate

  To determine if a gene-derived individualized treatment approach in patients with drug-resistant TB will improve culture negative survival rates at 6 months post treatment initiation

  24 months

• Culture negative survival rate

  To determine if a gene-derived individualized treatment approach in patients with drug-resistant TB will improve culture negative survival rates at 6 months post treatment initiation

  30 months

Secondary Outcomes (7)

• Tuberculosis treatment outcomes

  30 months

• Rates of adverse events

  30 months

• Characterization of multi drug-resistant tuberculosis strains

  30 months

• Drug Concentration

  30 months

• Measure of adherence

  30 months

Study Arms (2)

Individualized treatment for drug resistant tuberculosis

EXPERIMENTAL

Patients with drug resistance will have whole genome sequencing performed on the respective positive MGIT sample. An individualized TB treatment regimen will be provided to patients based on the whole genome sequencing results

Drug: Individualized TB treatment with multiple drugs

Standard treatment regimen for drug resistant tuberculosis

ACTIVE COMPARATOR

As per South African Department of Health Standard of Care for the treatment of drug resistant tuberculosis

Drug: Standardized TB treatment with multiple drugs

Interventions

Individualized TB treatment with multiple drugs DRUG

Patients with drug-resistant TB will receive a combination of any of the following drugs based on whole genome sequencing: rifampicin, rifabutin, isoniazid, high dose isoniazid, pyrazinamide, ethambutol, levofloxacin, moxifloxacin, ofloxacin, gatifloxacin, amikacin, capreomycin, kanamycin, streptomycin, ethionamide, prothionamide, cycloserine, terizidone, pretomanid, linezolid, sutezolid, clofazimine, bedaquiline, delaminid, para-aminosalicylic acid, imipenem/cilastatin, meropenem, amoxicillin/clavulanate, clarithromycin, azithromycin and thioacetazone

Individualized treatment for drug resistant tuberculosis

Standardized TB treatment with multiple drugs DRUG

Patients with drug-resistant TB with receive a combination of any of the following drugs based on South African Department of Health guidelines: rifampicin, rifabutin, isoniazid, high dose isoniazid, pyrazinamide, ethambutol, levofloxacin, moxifloxacin, ofloxacin, gatifloxacin, amikacin, capreomycin, kanamycin, streptomycin, ethionamide, prothionamide, cycloserine, terizidone, pretomanid, linezolid, sutezolid, clofazimine, bedaquiline, delaminid, para-aminosalicylic acid, imipenem/cilastatin, meropenem, amoxicillin/clavulanate, clarithromycin, azithromycin and thioacetazone

Standard treatment regimen for drug resistant tuberculosis

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults ≥ 18 years of age
• Pulmonary Tuberculosis
• Microbiological confirmation \[e.g. GeneXpert Mycobacterium Tuberculosis (MTB) detected and Rifampicin (RIF) resistant and / Line Probe Assay (LPA)\] of Multi drug-resistant tuberculosis (MDR-TB) / Pre-Extremely drug-resistant tuberculosis (Pre-XDR-TB) / Extremely drug-resistant tuberculosis (XDR-TB)
• Capacity for providing informed consent
• HIV status - HIV infected and uninfected patients are allowed in the study:
• Patients already on antiretroviral treatment (ART) will be allowed in the study. The antiretroviral treatment regimen will be evaluated for any contraindications to the drugs used.
• HIV infected patients at any CD4 count irrespective of antiretroviral treatment commencement and duration will be included in the study

You may not qualify if:

• Persons suffering from any serious acute condition.
• Any other chronic or clinically significant medical condition that in the opinion of the attending clinician would render the patient unsuitable for participation in the study.

Sponsors & Collaborators

• Centre for the AIDS Programme of Research in South Africa: lead

Study Sites (1)

King Dinuzulu Hospital

Durban, KwaZulu-Natal, South Africa

Location

Related Publications (3)

• Musser JM. Antimicrobial agent resistance in mycobacteria: molecular genetic insights. Clin Microbiol Rev. 1995 Oct;8(4):496-514. doi: 10.1128/CMR.8.4.496.

  PMID: 8665467 BACKGROUND

• Outhred AC, Jelfs P, Suliman B, Hill-Cawthorne GA, Crawford AB, Marais BJ, Sintchenko V. Added value of whole-genome sequencing for management of highly drug-resistant TB. J Antimicrob Chemother. 2015 Apr;70(4):1198-202. doi: 10.1093/jac/dku508. Epub 2014 Dec 9.

  PMID: 25492392 BACKGROUND

• Maseko TG, Ngubane S, Letsoalo M, Rambaran S, Archary D, Samsunder N, Perumal R, Chinappa S, Padayatchi N, Naidoo K, Sivro A. Higher plasma interleukin - 6 levels are associated with lung cavitation in drug-resistant tuberculosis. BMC Immunol. 2023 Aug 31;24(1):26. doi: 10.1186/s12865-023-00563-2.

  PMID: 37653422 DERIVED

MeSH Terms

Conditions

Tuberculosis, Multidrug-Resistant

Condition Hierarchy (Ancestors)

Tuberculosis; Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Study Officials

• Nesri Padayatchi, MBChB, PhD

  Centre for the AIDS Programme of Research in South Africa

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Deputy Director

Model Details: Patients randomized to the intervention receive a individualized tuberculosis treatment based on whole genome sequencing and the patients randomized to the control receive the standard of care tuberculosis treatment

Study Record Dates

• First Submitted: July 27, 2017
• First Posted: August 2, 2017
• Study Start: June 14, 2017
• Primary Completion: December 19, 2022
• Study Completion: December 19, 2022
• Last Updated: September 1, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: Beginning 9 months and ending 36 months following article publication
• Access Criteria: Investigators wishing to access data from this study will need to contact the PI to request the data. Requests may be submitted up to 36 months following article publication. Investigators will need to complete a proposal for how the data will be used. The proposal will be reviewed by the CAPRISA Scientific Review Committee and the CAPRISA Executive Committee.

Locations

ZA (1)