A Phase 3 interventional study of Isoniazid (H) and Rifampicin (R) in Tuberculosis (TB), sponsored by University College, London. Recruiting at 4 sites in 3 countries. Open to participants aged 16 Years and older. Per ClinicalTrials.gov, last updated 2026-10-26.
Sponsored by University College, London · Phase 3, Interventional, and Treatment
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.
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.
Increasingly, countries are adopting community-based chest X-ray (CXR) screening strategies to identify people with TB at an early stage, often before they have symptoms. However, a significant proportion of individuals with radiographic abnormalities suggestive of TB are not bacteriologically confirmed due to limitations in sputum-based diagnostics or inability to produce sputum. These individuals are often diagnosed with "bacteriologically unconfirmed TB," and there is currently no consensus on how best to manage them.
The RADIO-TB trial is a multi-country, multi-arm, phase 3 clinical trial designed to address this critical evidence gap. The trial aims to determine the optimal treatment duration for individuals with radiographic evidence of TB who do not have bacteriological confirmation and are identified through active case finding (ACF) using CXR and computer-aided detection (CAD) software. The study is being conducted in South Africa, Zimbabwe, and Pakistan. Recruitment for the trial will be conducted alongside existing programatic CXR-based TB ACF activity taking place in these countries.
RADIO-TB uses a pragmatic, open-label, randomized design with six parallel arms. Participants are randomized to one of the following 6 arms in a ratio 1:1:1:1:1:2.
Arm A. 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 (control-A).
Arm B. Immediate start of 20 weeks (approx. 5 months) TB treatment - 2HRZE/3HR. Arm C. Immediate start of 16 weeks (approx. 4 months) TB treatment - 2HRZE/2HR. Arm D. Immediate start of 12 weeks (approx. 3 months) TB treatment - 2HRZE/1HR. Arm E. Immediate start of 8 weeks (approx. 2 months) TB treatment - 2HRZE. Arm F. No initial treatment, deferred if progression - 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 (control-F).
The trial employs a Response Over Continuous Intervention (ROCI) design, which allows for the estimation and modelling of the duration-response curve and a more precise and efficient identification of the shortest non-inferior treatment duration compared to the standard 24-week regimen. The study hypothesis is that those with radiographically apparent, bacteriologically unconfirmed TB identified through ACF, immediate TB treatment with duration that is 8 weeks or longer, but less than 24 weeks, will be: (A) Non-inferior to treatment of 24 weeks duration (Arm A) at a 5% non-inferiority margin and (B) Superior to no initial treatment (Arm F) to prevent unfavourable TB outcomes.
The trial will enrol 784 participants aged 16 years and older who have undergone CXR-based TB ACF locally and found to have a CAD score above a locally defined threshold for TB investigation and either sputum negative by a WHO-approved rapid molecular test for TB or are unable to produce sputum. Key exclusion criteria are: a history of prior pulmonary TB, evidence of extra-pulmonary TB, clinical indication for immediate full-course treatment or an alternative cause for the CXR abnormalities more likely than TB. People who are HIV-infected will be eligible if their CD4 count is ≥200/mm3 and they on established on anti-retroviral therapy (ART). The CAD software used for screening will be those used locally in the existing ACF programmes according to international recommendation and national approvals. At the end of the study CXR will be re-analysed for all available CAD software to aid generalisability of findings.
All participants will undergo comprehensive baseline assessments, including clinical evaluation, induced sputum culture, blood and respiratory sampling for novel diagnostics. They are followed for 78 weeks with scheduled clinical evaluations, repeat chest X-ray, repeat microbiological testing, and quality-of-life assessments. Where necessary participants will be investigated for conditions other than TB.
The primary outcome measure for the trial is the proportion with unfavourable outcomes defined as requiring initiation of TB treatment after the week 0 visit for either bacteriologically confirmed TB or clinical/radiological progression without bacteriological confirmation. The trial also evaluates safety, tolerability of treatment; the impact on lung function, chest X-ray changes and quality of life; the frequency and timing of diagnoses other than TB; and the development of drug resistance. In addition, the study includes ancillary components to (1) assess the cost-effectiveness of different treatment strategies, (2) model the impact of different strategies on TB transmission and (3) evaluate novel diagnostic tools that may improve the early identification and confirmation of TB.
The RADIO-TB trial is sponsored by University College London (UCL) and funded by the Wellcome Trust. It is coordinated by the UCL Institute of Clinical Trials and Methodology (ICTM) in collaboration with national TB programs, academic institutions, and community partners in the participating countries. The trial incorporates robust patient and public involvement (PPI) mechanisms to ensure that the research is aligned with community priorities and that findings are disseminated in accessible and impactful ways.
By generating high-quality evidence on the optimal management of bacteriologically unconfirmed TB, the RADIO-TB trial aims to inform national and international TB treatment guidelines. The results will support more individualised and evidence-based approaches to TB care, improve patient outcomes, and contribute to global efforts to end the TB epidemic.
1,170 studies on the registry are indexed under Tuberculosis; 175 are open to participants now.
This study's planned enrollment of 784 is above the median of 150 across 820 interventional studies indexed under Tuberculosis.
Browse Tuberculosis studies →University College, London is the lead sponsor of 651 studies on the registry; 149 are open to participants now.
Of its 6 completed or terminated interventional studies of FDA-regulated products, 2 (33%) have results posted.
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Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
The number of CD4 cells, a type of white blood cell, in a given amount of blood. It is used to follow how well the immune system is doing in HIV.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
CD4 count
The number of CD4 cells, a type of white blood cell, in a given amount of blood. It is used to follow how well the immune system is doing in HIV.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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)
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)
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)
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)
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)
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
H, weight based, 150-375mg
R, weight based, 300-750mg
Z, weight based, 800-2000mg
E weight based, 550-1375mg
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
Time to (re-)treatment
Time frame: Over 78 weeks post-randomisation
Proportion of participants with bacteriological confirmation for Mtb
Time frame: Over 78 weeks post-randomisation
Proportion of participants initiated on TB treatment for symptomatic TB
Time frame: Over 78 weeks post-randomisation
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
Forced expiratory volume in 1 second (FEV1)
Lung function test determined by spirometry
Time frame: At 72 weeks
Forced vital capacity (FVC)
Lung function test determined by spirometry
Time frame: At 72 weeks
FEV1/FVC ratio
Lung function test determined by spirometry
Time frame: At 72 weeks
Total time on TB treatment
Time frame: Over 78 weeks
Number Needed to Treat to prevent unfavourable outcome
Time frame: Over 78 weeks
All-cause mortality
Time frame: Over 78 weeks
Proportion of participants experiencing Grade 2/3/4 Adverse Events (AE) (and the subset which are treatment emergent) according to DAIDS criteria
Time frame: Over 24 and 78 weeks
Proportion of participants experiencing Serious Adverse Events
Time frame: Over 24 and 78 weeks
Proportion of participants experiencing Hepatotoxicity AE of Special Interest
Time frame: Over 24 and 78 weeks
Proportion of participants permanently stopping treatment due to an AE of any grade (AESI)
Time frame: Over 78 weeks
Proportion of participants with final diagnosis of baseline CXR abnormality as non-TB
Time frame: Over 78 weeks
Time to non-TB diagnosis
Time frame: Over 78 weeks
Proportion who develop isoniazid and/or rifampicin resistant TB
Time frame: Over 78 weeks
EuroQol Visual Analogue Scale score
Scaled - 0 (worst imaginable health) to 100 (best imaginable health)
Time frame: Over 72 weeks
Short Form 36 (SF-36) score
36 item questionnaire evaluating 8 health domains. Domains are scored 0 (worse health) to 100 (better health).
Time frame: At weeks 0, 8, 16, 24, 48, 72
Chronic Obstructive Pulmonary Disease Assessment Test (CAT) score
8 item questionnaire. Individual question scores are summed to provide a total score ranging from 0 to 40. A higher score indicates a greater impact of lung condition on their health and daily life.
Time frame: At 72 weeks
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
Extent of TB related symptoms determined by NCI-PRO-CTCAE custom survey
Time frame: Over 24 and 72 weeks
Extent of treatment tolerability determined by NCI-PRO-CTCAE custom survey
Time frame: Over 24 and 72 weeks
Quality adjusted Time without Symptoms and Toxicity (Q-TWiST)
Time frame: Over 78 weeks
Extent of treatment acceptance determined by the PROMIS Scale v1.0 Medication Adherence questionnaire
Time frame: Over 78 weeks
Plan to share: Yes — Plan to upload IPD to public repository e.g. WHO IPD or TB-PACTS
Supporting information: Study protocol
Time frame: After primary publication (est Q4 2029)
Access criteria: Via application to the IPD repository
No publications or documents are linked to this record.
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
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Studies of the drugs tested here: Isoniazid · Rifampin · Pyrazinamide · Ethambutol