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

ConditionTuberculosis (TB)
Trial statusNot yet recruiting
Trial phasePhase 3
Trial typeInterventional
Biological sexAll
Age16+
SponsorUniversity College, London

About this trial

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

Participants in the trial will be randomized into six groups: five receiving immediate standard TB treatment of varying durations (8 to 24 weeks), and one receiving deferred treatment with close monitoring. Deferred treatment will be initiated only if clinical deterioration occurs or TB is later confirmed. Participants will be closely followed for 78 weeks with at least 11 clinic visits.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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

Disqualifiers

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

Trial design

Design model

Parallel

Treatments tested in this trial

  • Isoniazid (H)

    Drug

    H, weight based, 150-375mg

  • Rifampicin (R)

    Drug

    R, weight based, 300-750mg

  • Pyrazinamide (Z)

    Drug

    Z, weight based, 800-2000mg

  • Ethambutol (E)

    Drug

    E weight based, 550-1375mg

Treatment groups

784 Participants
are divided into 6 treatment groups

6

Treatment groups

See each treatment group below.

Group A: Arm A. Immediate start of 24 weeks (approx. 6 months) TB treatmentActive comparator 4 interventions
Group B: Arm B. Immediate start of 20 weeks (approx. 5 months) TB treatmentExperimental treatment 4 interventions
Group C: Arm C. Immediate start of 16 weeks (approx. 4 months) TB treatmentExperimental treatment 4 interventions
Group D: Arm D. Immediate start of 12 weeks (approx. 3 months) TB treatmentExperimental treatment 4 interventions
Group E: Arm E. Immediate start of 8 weeks (approx. 2 months) TB treatmentExperimental treatment 4 interventions
Group F: Arm F. No initial treatment, deferred if progression.No intervention 0 interventions

Trial outcomes

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

Time frame
Over 78 weeks post-randomisation

Secondary outcomes

1

Time to (re-)treatment

Time frame
Over 78 weeks post-randomisation
2

Proportion of participants with bacteriological confirmation for Mtb

Time frame
Over 78 weeks post-randomisation
3

Proportion of participants initiated on TB treatment for symptomatic TB

Time frame
Over 78 weeks post-randomisation
4

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

Higher score indicates a higher probability of TB related abnormality.

Time frame
At weeks 8, 36 and 72

Other outcomes

1

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

Will include TB-related scores provided by software and other abnormality scores.

Time frame
Over 72 weeks
2

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

Time frame
Over 24 and 72 weeks
3

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

Time frame
Over 24 and 72 weeks
4

Quality adjusted Time without Symptoms and Toxicity (Q-TWiST)

Time frame
Over 78 weeks

Sponsors and contacts

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University College, London

Lead sponsor

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

Source ClinicalTrials.gov

This trial is not recruiting at the moment. You can still explore other options: