Sequencing Mycobacteria and Algorithm-determined Resistant Tuberculosis Treatment Trial

NCT05017324 | Unknown DMC

• 3 other identifiers: AUR1-11-248T001018N2020-004084-10
• Study Type: interventional
• Target: 248
• Locations: 1 country
• Sites: 1

Brief Summary

The primary aim of this pragmatic trial is to determine the effectiveness of a Whole Genome Sequencing (WGS) Drug Sensitivity Testing (DST) strategy to guide individualised treatment of rifampicin resistant tuberculosis (RR-TB) patients. The primary objective is to determine the effectiveness of this WGS DST strategy in patients diagnosed with RR-TB. We will additionally perform an exploratory health economics evaluation of both arms, and will determine the feasibility of the WGS DST strategy.

Conditions

Rifampicin Resistant Tuberculosis; Drug-resistant Tuberculosis; Multidrug Resistant Tuberculosis; Pulmonary Tuberculoses

Keywords

Whole Genome Sequencing; Drug Resistant Tuberculosis

Outcome Measures

Primary Outcomes (1)

• The Effectiveness of a WGS DST strategy for individualisation of RR-TB treatment

  The effectiveness will be determined by the rate of change in time to positivity (TTP) over 6 months in the Mycobacterial Growth Indicator Tuber (MGIT) system \[time from: Day 0 to Week 24\]. The effectiveness of the WGS DST strategy will be determined by the rate of change in TTP in liquid media MGIT cultures of sputum samples collected during the first 6 months of treatment. The TTP will be used to determine the change in mycobacterial load using a non-linear mixed effect time-to-event model that provides a longitudinal representation of mycobacterial load (measured as TTP in MGIT) at weeks 2, 3, 4, 5, 6, 7, 8, 12, 16, 20 and 24

  Day 0 to month 6 (6 months)

Secondary Outcomes (2)

• Health economic evaluation of a WGS DST strategy for individualization of RR-TB treatment

  Start of treatment to end of treatment (which may vary from 6 months to over 11 months)

• Impact of WGS strategy for individualisation of RR-TB treatment on Health related Quality of Life (HRQOL)

  Start of treatment to end of treatment (which may vary from 6 months to over 11 months)

Study Arms (2)

WGS DST strategy

EXPERIMENTAL

WGS DST strategy for diagnosing the TB drug resistance profile and an individualised RR-TB treatment recommendation

Device: WGS DST strategy

Standard of Care

NO INTERVENTION

Standard of care diagnosis of the drug resistance profile and individualised treatment

Interventions

WGS DST strategy DEVICE

WGS DST strategy for diagnosing the TB drug resistance profile and an algorithm-determined individualised RR-TB treatment recommendation

WGS DST strategy

Eligibility Criteria

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

You may qualify if:

• Diagnosed with RR-TB
• Diagnosed with pulmonary TB (PTB) or PTB plus extra-pulmonary TB (EPTB)
• ≥18 years of age
• Able to sign informed consent
• Not on TB treatment at time of enrolment

You may not qualify if:

• Patients diagnosed EPTB without pulmonary involvement
• Patients with TB Meningitis or TB of the bone.
• 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.

Sponsors & Collaborators

• Universiteit Antwerpen: lead
• Aurum Institute: collaborator
• University of Stellenbosch: collaborator
• University of the Free State: collaborator
• Free State Department of Health: collaborator

Study Sites (1)

Free State Department of Health Clinics

Bloemfontein, Free State, South Africa

RECRUITING

Related Publications (1)

• Van Rie A, De Vos E, Costa E, Verboven L, Ndebele F, Heupink TH, Abrams S; SMARTT team; Fanampe B, Van der Spoel Van Dyk A, Charalambous S, Churchyard G, Warren R. Sequencing Mycobacteria and Algorithm-determined Resistant Tuberculosis Treatment (SMARTT): a study protocol for a phase IV pragmatic randomized controlled patient management strategy trial. Trials. 2022 Oct 8;23(1):864. doi: 10.1186/s13063-022-06793-w.

  PMID: 36209235 DERIVED

MeSH Terms

Conditions

Tuberculosis, Multidrug-Resistant; Tuberculosis, Pulmonary

Condition Hierarchy (Ancestors)

Tuberculosis; Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Gavin Churchyard, PhD, MD

  Aurum Institute

  PRINCIPAL INVESTIGATOR

• Annelies Van Rie, PhD, MD

  Universiteit Antwerpen

  PRINCIPAL INVESTIGATOR

• Rob M Warren, PhD

  Stellenbosch University, MRC

  PRINCIPAL INVESTIGATOR

• Salome Charalambous, PhD

  Aurum Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Elise De Vos, MSc

CONTACT

0032477715350; elise.devos@uantwerpen.be

Annelies Van Rie, PhD, MD

CONTACT

annelies.vanrie@uantwerpen.be

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: HEALTH SERVICES RESEARCH
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: Randomized Controled Phase 4 pragmatic single blinded medical device trial.

Study Record Dates

• First Submitted: April 22, 2021
• First Posted: August 23, 2021
• Study Start: September 21, 2021
• Primary Completion: December 1, 2022
• Study Completion: January 1, 2025
• Last Updated: October 15, 2021

Record last verified: 2021-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: From publication of the results of the primary up to 5 years thereafter
• Access Criteria: WGS: available on European Nucleotide Archive (ENA) Other data: access will be provided to researchers who have obtained Institutional Review Board (IRB) approval for analyses

Locations

ZA (1)