Sequencing Tuberculosis bacteria's DNA and its use for Resistant Tuberculosis Treatment; a pragmatic randomised controlled trial

Phase 1

• Conditions: Rifampicin resistant (RR-TB) and drug resistant (DR-TB) tuberculosis; MedDRA version: 20.1Level: PTClassification code 10049031Term: Genotype drug resistance testSystem Organ Class: 10022891 - Investigations; MedDRA version: 20.1Level: PTClassification code 10048723Term: Multiple-drug resistanceSystem Organ Class: 10018065 - General disorders and administration site conditions; MedDRA version: 20.0Level: PTClassification code 10059866Term: Drug resistanceSystem Organ Class: 10018065 - General disorders and administration site conditions; MedDRA version: 20.0Level: LLTClassification code 10004052Term: Bacterial resistanceSystem Organ Class: 100000004862; MedDRA version: 20.0Level: LLTClassification code 10038637Term: Resistance bacterialSystem Organ Class: 100000004862; MedDRA version: 20.1Level: LLTClassification code 10028152Term: Multi-antibiotic resistanceSystem Organ Class: 100000004862; MedDRA version: 20.0Level: LLTClassification code 10070974Term: Antibiotic resistance testSystem Organ Class: 10022891 - Investigations; Therapeutic area: Health Care [N] - Health Services Administration [N04]

• Registration Number: EUCTR2020-004084-10-Outside-EU/EEA
• Lead Sponsor: Flemisch Fund for Scientific Research - Fonds voor Wetenschappelijk Onderzoek

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2022-05-16
• Last Update Posted: 23 May 2022

Recruitment & Eligibility

• Status: A
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

-Diagnosed with RR-TB on Xpert Ultra
Justification: The target population for the use of WGS if people with confirmed rifampicin resistant TB. Xpert Ultra is the initial test used for diagnosis of TB and RR-TB in South Africa.
-Diagnosed with pulmonary TB (PTB) or PTB plus extra-pulmonary TB (EPTB)
Justification: To assess the main outcome measure (time to culture conversion) weekly samples must be collected for Mtb culture. This is only possible in people with PTB.
-=18 years of age
Justification: collection of sputum samples in children is difficult and children most often have paucibacillary TB. We therefore propose to limit the study to adults with RR-TB.
-Able to sign informed consent
Justification: This is not an emergency research study. All people will thus need to complete the written informed consent process before any trial related procedure.
-Not on TB treatment at time of enrolment
Justification: There are two main reasons to limit enrolment to people not yet on TB treatment at time of enrolment: (1) In this phase IV pragmatic trial, we aim to study the use of WGS as this will most be implemented in routine care. We believe that WGS would be the first ‘reflex’ DST assay that will be performed after a RR-TB diagnosis. WGS would thus occur in people not yet on TB treatment, (2) On treatment, the myco-bacterial burden rapidly decreases, possibly reducing the success rate of WGS.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 248
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

-Patients diagnosed EPTB without pulmonary involvement
Justification: the primary endpoint of the trial is time to culture conversion. This requires collection of weekly samples for Mtb culture. This is not feasible and too burdensome for patients with EPTB without pulmonary TB as this would require weekly collection of an invasive sample.
-Patients with TB Meningitis or TB of the bone.
Justification: the treatment of patients with TB meningitis or TB of the bone is complicated and should always be decided by a exert committee. For optimal safety of these patients, they will be excluded from participation in this trial.
-Has any condition that, in the opinion of the investigator or physician, would preclude provision of informed consent, make participation in the study unsafe, complicate interpretation of study outcome data, interfere with achieving the study objectives or compromise patient safety.
Justification: this exclusion criteria aims to ensure optimal patient safety and scientific rigor.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified