Optimal Treatment Duration for Radiographically Apparent, Bacteriologically Unconfirmed TB, Identified Through Active Case Finding (RADIO-TB Trial)

NCT07163143 | Not Yet Recruiting Phase 3 DMC

• 1 other identifier: 314897/Z/24/Z
• Study Type: interventional
• Target: 784
• Locations: 3 countries
• Sites: 4

Brief Summary

People living in high TB burden communities who undergo active case finding for TB may have chest X-ray changes suggestive of TB but their sputum test can be negative for the TB bacteria or they are unable to provide a sputum sample. This means they have bacteriologically unconfirmed TB. These individuals often have minimal or no symptoms and face uncertainty in clinical management-either receiving full 24-weeks TB treatment or often being discharged without treatment, risking loss to follow-up. The RADIO-TB trial aims to address the following main questions in relation to people with bacteriologically unconfirmed TB.

1. 1.What is the risk of progression if treatment is not immediately started but there is close and careful follow-up over 78 weeks?
2. 2.If treatment is started immediately what is the shortest duration of TB treatment that is as effective as the standard 24-week TB treatment?
3. 3.Are there better tests to confirm TB than the current routinely used, sputum-based tests?
4. 4.What is the cost effectiveness of different treatment strategies and what might the impact on transmission be within communities?

Conditions

Tuberculosis (TB)

Keywords

Treatment duration; Radiographically apparent TB; Bacteriologically unconfirmed TB; Response over continuous intervention (ROCI); Active case finding; Asymptomatic; Subclinical; Chest X-ray; Screening; Computer Aided Detection (CAD)

Outcome Measures

Primary Outcomes (1)

• Proportion of participants with an unfavourable TB outcome

  Unfavourable outcome = requiring initiation of TB treatment after the week 0 visit for either bacteriologically confirmed TB or clinical/radiological progression without bacteriological confirmation

  Over 78 weeks post-randomisation

Secondary Outcomes (20)

• Time to (re-)treatment

  Over 78 weeks post-randomisation

• Proportion of participants with bacteriological confirmation for Mtb

  Over 78 weeks post-randomisation

• Proportion of participants initiated on TB treatment for symptomatic TB

  Over 78 weeks post-randomisation

• Computer Aided Detection (CAD) software score (TB related)

  At weeks 8, 36 and 72

• Forced expiratory volume in 1 second (FEV1)

  At 72 weeks

Other Outcomes (5)

• Change in Computer Aided Detection software scores (multi-domain)

  Over 72 weeks

• Extent of TB related symptoms determined by NCI-PRO-CTCAE custom survey

  Over 24 and 72 weeks

• Extent of treatment tolerability determined by NCI-PRO-CTCAE custom survey

  Over 24 and 72 weeks

Study Arms (6)

Arm A. Immediate start of 24 weeks (approx. 6 months) TB treatment

ACTIVE COMPARATOR

Immediate start of 24 weeks (approx. 6 months) TB treatment comprised of 8 weeks (approx. 2 months) isoniazid, rifampicin, pyrazinamide and ethambutol (2HRZE) followed by 16 weeks (approx. 4 months) of isoniazid and rifampicin (4HR) - 2HRZE/4HR

Drug: Isoniazid (H); Drug: Rifampicin (R); Drug: Pyrazinamide (Z); Drug: Ethambutol (E)

Arm B. Immediate start of 20 weeks (approx. 5 months) TB treatment

EXPERIMENTAL

Immediate start of 20 weeks (approx. 5 months) TB treatment comprised of 8 weeks (approx. 2 months) isoniazid, rifampicin, pyrazinamide and ethambutol (2HRZE) followed by 12 weeks (approx. 3 months) of isoniazid and rifampicin (3HR) - 2HRZE/3HR

Drug: Isoniazid (H); Drug: Rifampicin (R); Drug: Pyrazinamide (Z); Drug: Ethambutol (E)

Arm C. Immediate start of 16 weeks (approx. 4 months) TB treatment

EXPERIMENTAL

Immediate start of 16 weeks (approx. 4 months) TB treatment comprised of 8 weeks (approx. 2 months) isoniazid, rifampicin, pyrazinamide and ethambutol (2HRZE) followed by 8 weeks (approx. 2 months) of isoniazid and rifampicin (2HR) - 2HRZE/2HR

Drug: Isoniazid (H); Drug: Rifampicin (R); Drug: Pyrazinamide (Z); Drug: Ethambutol (E)

Arm D. Immediate start of 12 weeks (approx. 3 months) TB treatment

EXPERIMENTAL

Immediate start of 12 weeks (approx. 6 months) TB treatment comprised of 8 weeks (approx. 2 months) isoniazid, rifampicin, pyrazinamide and ethambutol (2HRZE) followed by 4 weeks (approx. 1 month) of isoniazid and rifampicin (1HR) - 2HRZE/1HR

Drug: Isoniazid (H); Drug: Rifampicin (R); Drug: Pyrazinamide (Z); Drug: Ethambutol (E)

Arm E. Immediate start of 8 weeks (approx. 2 months) TB treatment

EXPERIMENTAL

Immediate start of 8 weeks (approx. 2 months) TB treatment comprised of isoniazid, rifampicin, pyrazinamide and ethambutol (2HRZE)

Drug: Isoniazid (H); Drug: Rifampicin (R); Drug: Pyrazinamide (Z); Drug: Ethambutol (E)

Arm F. No initial treatment, deferred if progression.

NO INTERVENTION

No initial treatment - if during close follow-up there is bacteriological confirmation and/or clinical/radiological progression, to start 24 weeks (approx. 6 months) TB treatment - 2HRZE/4HR

Interventions

Isoniazid (H) DRUG

H, weight based, 150-375mg

Arm A. Immediate start of 24 weeks (approx. 6 months) TB treatment; Arm B. Immediate start of 20 weeks (approx. 5 months) TB treatment; Arm C. Immediate start of 16 weeks (approx. 4 months) TB treatment; Arm D. Immediate start of 12 weeks (approx. 3 months) TB treatment; Arm E. Immediate start of 8 weeks (approx. 2 months) TB treatment

Rifampicin (R) DRUG

R, weight based, 300-750mg

Arm A. Immediate start of 24 weeks (approx. 6 months) TB treatment; Arm B. Immediate start of 20 weeks (approx. 5 months) TB treatment; Arm C. Immediate start of 16 weeks (approx. 4 months) TB treatment; Arm D. Immediate start of 12 weeks (approx. 3 months) TB treatment; Arm E. Immediate start of 8 weeks (approx. 2 months) TB treatment

Pyrazinamide (Z) DRUG

Z, weight based, 800-2000mg

Arm A. Immediate start of 24 weeks (approx. 6 months) TB treatment; Arm B. Immediate start of 20 weeks (approx. 5 months) TB treatment; Arm C. Immediate start of 16 weeks (approx. 4 months) TB treatment; Arm D. Immediate start of 12 weeks (approx. 3 months) TB treatment; Arm E. Immediate start of 8 weeks (approx. 2 months) TB treatment

Ethambutol (E) DRUG

E weight based, 550-1375mg

Arm A. Immediate start of 24 weeks (approx. 6 months) TB treatment; Arm B. Immediate start of 20 weeks (approx. 5 months) TB treatment; Arm C. Immediate start of 16 weeks (approx. 4 months) TB treatment; Arm D. Immediate start of 12 weeks (approx. 3 months) TB treatment; Arm E. Immediate start of 8 weeks (approx. 2 months) TB treatment

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged ≥16 years old on day of randomisation
• ≥25kg in weight on day of randomisation
• Participation in community or facility-based active case finding for TB by CXR
• Digital CXR with Computer Aided Detection software score above threshold for sputum investigation for Mtb according to local guidance ≤21 days prior to randomisation
• Attempted sputum collection for testing by WHO approved rapid molecular test for Mtb at active case finding and at screening

You may not qualify if:

• Sputum sample from active case finding or screening confirmed as positive for Mtb by WHO approved rapid molecular test for Mtb
• Previous history of pulmonary TB
• TB preventive therapy taken within the last 6 months
• \>1 dose of treatment with anti-tuberculous activity taken in the 21 days prior to randomisation
• HIV infected, unless CD4 ≥200 cells/mm3 and on anti-retroviral therapy for at least 8 weeks
• Pregnancy (confirmed by high sensitivity urine test)
• Contraindication to study drug
• Investigator concern for potential extra-pulmonary TB with the exceptions of (a) intrathoracic lymphadenopathy; and/or (b) small pleural effusion of limited extent, neither felt to require invasive diagnostic sampling
• CXR changes considered more likely to relate to a condition other than untreated TB by investigator
• Investigator assessment of an immediate requirement for full 24-weeks standard TB treatment
• Investigator assessment of unacceptable risks to potential participant from study entry
• No fixed home address
• Unable to participate in the full duration of study follow-up

Sponsors & Collaborators

• University College, London: lead
• National University of Medical Sciences, Pakistan: collaborator
• Aurum Institute: collaborator
• Biomedical Research and Training Institute, Zimbabwe: collaborator
• Foundation for Innovative New Diagnostics, Switzerland: collaborator
• KTH Royal Institute of Technology: collaborator
• London School of Hygiene and Tropical Medicine: collaborator
• Wits Health Consortium (Pty) Ltd: collaborator

Study Sites (4)

National University of Medical Sciences

Islamabad, Pakistan

Location

Clinical HIV Research Unit, Wits Health Consortium

Johannesburg, South Africa

Location

The Aurum Institute

Johannesburg, South Africa

Location

Bulawayo City Health

Bulawayo, Zimbabwe

Location

MeSH Terms

Conditions

Tuberculosis

Interventions

Isoniazid; Protons; Rifampin; Pyrazinamide; Ethambutol

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Hydrazines; Organic Chemicals; Isonicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring; Cations, Monovalent; Cations; Ions; Electrolytes; Inorganic Chemicals; Hydrogen; Elements; Gases; Nucleons; Elementary Particles; Physical Phenomena; Rifamycins; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds; Pyrazines; Ethylenediamines; Diamines; Polyamines; Amines

Central Study Contacts

Hanif Esmail, Prof

CONTACT

+44 20 7670 4700; h.esmail@ucl.ac.uk

Mags Thomason, Dr

CONTACT

+44 20 7670 4615; m.thomason@ucl.ac.uk

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 1, 2025
• First Posted: September 9, 2025
• Study Start: November 1, 2025
• Primary Completion (Estimated): November 1, 2028
• Study Completion (Estimated): April 1, 2029
• Last Updated: September 9, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: After primary publication (est Q4 2029)
• Access Criteria: Via application to the IPD repository

Locations

ZA (2); ZI (1); PA (1)