Pulmonary TBPhase 3RIFAstratNCT07118696
Evaluating a Shorter, Rifampicin-Based Treatment for People With Less Severe Tuberculosis Disease
A Phase 3 study testing Extra 600mg of Rifampicin in people with Pulmonary TB, run by Hamilton Health Sciences Corporation.
Trial summary
RIFAstrat is a Phase 3, double-blind, placebo-controlled, non-inferiority trial to compare the 6-month standard treatment for DS-TB with a 4-month optimised- rifampicin based regimen provided to individuals with limited disease severity. Read more about this study
- Who is it for?
- Ages 12 years and older
- Conditions the study is for
- Pulmonary TB
- What is being tested?
- Extra 600mg of Rifampicin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 1,000 participants
- Where
- No sites listed yet
- Study dates
- 1 Feb 2026to 31 Jan 2030
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Aged 12 years and over
- Clinical and/or radiological evidence of pulmonary TB
- At least one sputum specimen positive for M. tuberculosis by Xpert MTB/RIF or Ultra within 30 days of screening confirming rifampicin-sensitive TB
- Have limited TB disease defined as having a cycle threshold on sputum Xpert MTB/RIF or Ultra corresponding to 'medium' or below for bacterial burden at screening (where results from more than one test are available at screening, eligibility will be determined by the highest grade)
- Documentation of HIV status from a validated test performed within 30 days of screening or known to be HIV-positive
- Well enough to be treated as an outpatient
Who cannot join
- Received more than 7 days treatment for index TB episode
- Previous treatment for active TB disease in past 12 months
- M. tuberculosis with known resistance to rifampicin or isoniazid
- Weight < 30 kg at screening
- Sick with one or more WHO 'danger signs' at screening (respiratory rate > 30 breaths per minute, temperature > 39 ˚C, heart rate > 120 bpm, inability to walk unaided)
- Suspected or confirmed extra-pulmonary TB involving the central nervous system, bones, joints, abdomen, and/or pericardium (coexistent pleural or lymph node TB are not exclusions)
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- For participants living with HIV:
- Urinary lipoarabinomannan test positive at screening
- Requires protease inhibitor-based antiretroviral therapy, and/or long acting antiretrovirals cabotegravir/rilpivirine
- For participants of child-bearing potential: currently pregnant or not currently pregnant but unwilling to practice an effective method of contraception during study drug treatment
- Clinical evidence of acute hepatitis or advanced chronic liver disease (e.g. jaundice, signs of portal hypertension)
- Known end stage renal failure
- Active malignancy not in remission or had systemic chemotherapy within 2 years (except for non-melanomatous skin cancer)
- Contraindication to study medications because of known allergy or intolerance or unavoidable drug-drug interaction
- Other medical conditions, that, in the investigator's judgment, make study participation not in the individual's best interest
- Inability to attend follow up visits
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: Shortening TB Treatment With Optimised Rifampicin-Based Therapy and Disease Stratification: A Pragmatic Phase 3 Double-Blind Placebo-Controlled Randomised Trial (RIFAstrat)
RIFAstrat is a Phase 3, double-blind, placebo-controlled, non-inferiority trial to compare the 6-month standard treatment for DS-TB with a 4-month optimised- rifampicin based regimen provided to individuals with limited disease severity.
Read the detailed description
RIFAstrat is a Phase 3, double-blind, placebo-controlled, non-inferiority trial to compare the 6-month standard treatment for DS-TB with a 4-month optimised-rifampicin based regimen provided to individuals with limited disease severity.
Participants are eligible for the study if they are ≥12 years old with newly diagnosed rifampicin-susceptible pulmonary TB confirmed by rapid molecular testing (Xpert MTB/RIF or ultra) with a limited disease phenotype, defined as a cycle threshold on sputum Xpert MTB/RIF or Ultra corresponding to 'medium' or below for bacterial burden at screening. Broad eligibility criteria allow for enrolment of people living with HIV, diabetes, other common comorbidities.
- Conditions
- Pulmonary TB
- Being tested
- Extra 600mg of Rifampicin, Placebo
- Keywords
- Rifampicin, Treatment Shortening
- Medical subject headings
- Tuberculosis, Pulmonary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Extra 600mg of RifampicinDrug
Also called Experimental
Intervention group participants will receive standard treatment (RHZE), plus an optimised regimen consisting of RIfampicin at 20 mg/kg (additional 600mg rifampicin in each weight band) during a shortened treatment period of 16 weeks.
PlaceboDrug
Also called Control
The standard treatment regimen for DS-TB (rifampicin at 10 mg/kg and isoniazid for 6 months, plus pyrazinamide and ethambutol for the first 2 months; 2RHZE/4RH), with additional placebo for the first 4 months (16 weeks).
| Study group | Role | What they receive |
|---|---|---|
| 16-Week Regimen (Standard of Care Treatment + 600 mg of Rifampicin daily) | Experimental | Optimised regimen consisting of rifampicin at 20 mg/kg and isoniazid for 4 months (16 weeks), plus pyrazinamide and ethambutol for the first 2 months (2R20HZE/2R20H). Delivered as local standard of care (RHZE) plus 600mg (2 additional tablets) of rifampicin. Receives: Drug: Extra 600mg of Rifampicin |
| 24-Week Regimen (Standard of Care Treatment) + Placebo for 16 weeks | Placebo comparator | The standard treatment regimen for DS-TB (rifampicin at 10 mg/kg and isoniazid for 6 months, plus pyrazinamide and ethambutol for the first 2 months; 2RHZE/4RH), with additional placebo for the first 4 months (16 weeks). Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of participants with an unfavourable efficacy outcome (treatment failure, recurrence or re-treatment for poor treatment response) through week 48 in the intention to treat population.
Measured: From enrollment through to Week 48.
Secondary outcomes (11)
Death
Measured: 72 weeks
Treatment-emergent adverse events
Any adverse event leading to premature, permanent discontinuation of a study drug.
Treatment-related adverse events of special interest. Treatment-related SAEs.
Measured: 14 days after end of randomised treatment
Proportion of participants experiencing symptoms of interest during assigned treatment (tolerability)
Proportion of participants experiencing symptoms of interest during assigned treatment (tolerability)
Measured: 14 days after end of randomised treatment
Proportion of participants temporarily discontinuing assigned treatment (tolerability)
Proportion of participants temporarily discontinuing assigned treatment (tolerability)
Measured: 14 days after end of randomised treatement
Proportion of participants permanently discontinuing assigned treatment (tolerability)
Proportion of participants permanently discontinuing assigned treatment (tolerability)
Measured: 14 days after end of randomised treatment
Percentage of treatment doses taken (adherence)
Percentage of treatment doses taken (adherence)
Measured: 48 weeks
Total Time on Treatment
Total Time on Treatment
Measured: 72 weeks
Proportion of participants with acquired (post-baseline) drug resistance
Proportion of participants with acquired (post-baseline) drug resistance
Measured: 72 weeks
Scores on 5-level EQ-5D questionnaire
Scores on 5-level EQ-5D questionnaire
Measured: 72 weeks
Catastrophic costs and cost-effectiveness ratios, calculated using the adapted WHO patient costs survey
Catastrophic costs and cost-effectiveness ratios, calculated using the adapted WHO patient costs survey
Measured: 72 weeks
Respiratory disability measured by Medical Research Council (MRC) Dyspnea scale
Respiratory disability measured by Medical Research Council (MRC) Dyspnea scale
Measured: 72 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Aug 2025
- Study start1 Feb 2026 (estimated)
- Primary completion31 Jan 2029 (estimated)
- Study completion31 Jan 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pulmonary TBStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Participants will be randomised to the control or experimental arm in 1:1 ratio, stratified by site and HIV status. Intervention (experimental arm): an optimised regimen consisting of rifampicin at 20 mg/kg and isoniazid for 4 months (16 weeks), plus pyrazinamide and ethambutol for the first 2 months (2R20HZE/2R20H). Delivered as local standard of care (RHZE) plus 600mg (2 additional tablets) of rifampicin. Control: The standard treatment regimen for DS-TB (rifampicin at 10 mg/kg and isoniazid for 6 months, plus pyrazinamide and ethambutol for the first 2 months; 2RHZE/4RH), with additional placebo for the first 4 months (16 weeks).
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 1,000 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hamilton Health Sciences Corporation
- Sponsor type
- University, hospital or other
- Collaborators
- St George's, University of London, McMaster University
- Responsible party
- Sponsor
- Investigators
- Christopher Cousins, MBChB PhD, Principal investigator, St George's, University of LondonSean Wasserman, MBChB PhD, Principal investigator, St George's, University of LondonJohn Eikelboom, MBBS FRCPC, Principal investigator, Population Health Research Institute, McMaster University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07118696
- Sponsor's protocol ID
- 18513
- Acronym
- RIFAstrat
- Status last verified
- Jul 2025
- First submitted
- 25 Jul 2025
- Last updated
- 12 Aug 2025
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Shortening TB Treatment With Optimised Rifampicin-Based Therapy and Disease Stratification: A Pragmatic Phase 3 Double-Blind Placebo-Controlled Randomised Trial (RIFAstrat)
- ClinicalTrials.gov ID
- NCT07118696
- Acronym / sponsor ID
- RIFAstrat / 18513
- Conditions
- Pulmonary TB
- Keywords
- Rifampicin, Treatment Shortening
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 1,000 participants (estimated)
- Lead sponsor
- Hamilton Health Sciences CorporationUniversity, hospital or other
- Collaborators
- St George's, University of London, McMaster University
- Study start
- 1 Feb 2026 (estimated)
- Primary completion
- 31 Jan 2029 (estimated)
- Study completion
- 31 Jan 2030 (estimated)
- First posted
- 12 Aug 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
RIFAstrat is a Phase 3, double-blind, placebo-controlled, non-inferiority trial to compare the 6-month standard treatment for DS-TB with a 4-month optimised- rifampicin based regimen provided to individuals with limited disease severity.
Detailed description
RIFAstrat is a Phase 3, double-blind, placebo-controlled, non-inferiority trial to compare the 6-month standard treatment for DS-TB with a 4-month optimised-rifampicin based regimen provided to individuals with limited disease severity.
Participants are eligible for the study if they are ≥12 years old with newly diagnosed rifampicin-susceptible pulmonary TB confirmed by rapid molecular testing (Xpert MTB/RIF or ultra) with a limited disease phenotype, defined as a cycle threshold on sputum Xpert MTB/RIF or Ultra corresponding to 'medium' or below for bacterial burden at screening. Broad eligibility criteria allow for enrolment of people living with HIV, diabetes, other common comorbidities.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Participants will be randomised to the control or experimental arm in 1:1 ratio, stratified by site and HIV status. Intervention (experimental arm): an optimised regimen consisting of rifampicin at 20 mg/kg and isoniazid for 4 months (16 weeks), plus pyrazinamide and ethambutol for the first 2 months (2R20HZE/2R20H). Delivered as local standard of care (RHZE) plus 600mg (2 additional tablets) of rifampicin. Control: The standard treatment regimen for DS-TB (rifampicin at 10 mg/kg and isoniazid for 6 months, plus pyrazinamide and ethambutol for the first 2 months; 2RHZE/4RH), with additional placebo for the first 4 months (16 weeks).
| Arm | Type | Receives |
|---|---|---|
| 16-Week Regimen (Standard of Care Treatment + 600 mg of Rifampicin daily) | Experimental | Drug: Extra 600mg of RifampicinOptimised regimen consisting of rifampicin at 20 mg/kg and isoniazid for 4 months (16 weeks), plus pyrazinamide and ethambutol for the first 2 months (2R20HZE/2R20H). Delivered as local standard of care (RHZE) plus 600mg (2 additional tablets) of rifampicin. |
| 24-Week Regimen (Standard of Care Treatment) + Placebo for 16 weeks | Placebo comparator | Drug: PlaceboThe standard treatment regimen for DS-TB (rifampicin at 10 mg/kg and isoniazid for 6 months, plus pyrazinamide and ethambutol for the first 2 months; 2RHZE/4RH), with additional placebo for the first 4 months (16 weeks). |
Who may qualify
- Ages
- 12 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (6 listed)
- Aged 12 years and over
- Clinical and/or radiological evidence of pulmonary TB
- At least one sputum specimen positive for M. tuberculosis by Xpert MTB/RIF or Ultra within 30 days of screening confirming rifampicin-sensitive TB
- Have limited TB disease defined as having a cycle threshold on sputum Xpert MTB/RIF or Ultra corresponding to 'medium' or below for bacterial burden at screening (where results from more than one test are available at screening, eligibility will be determined by the highest grade)
- Documentation of HIV status from a validated test performed within 30 days of screening or known to be HIV-positive
Key exclusion criteria (16 listed)
- Received more than 7 days treatment for index TB episode
- Previous treatment for active TB disease in past 12 months
- M. tuberculosis with known resistance to rifampicin or isoniazid
- Weight < 30 kg at screening
- Sick with one or more WHO 'danger signs' at screening (respiratory rate > 30 breaths per minute, temperature > 39 ˚C, heart rate > 120 bpm, inability to walk unaided)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Extra 600mg of RifampicinAlso: ExperimentalIntervention group participants will receive standard treatment (RHZE), plus an optimised regimen consisting of RIfampicin at 20 mg/kg (additional 600mg rifampicin in each weight band) during a shortened treatment period of 16 weeks. | Drug | 16-Week Regimen (Standard of Care Treatment + 600 mg of Rifampicin daily) |
| PlaceboAlso: ControlThe standard treatment regimen for DS-TB (rifampicin at 10 mg/kg and isoniazid for 6 months, plus pyrazinamide and ethambutol for the first 2 months; 2RHZE/4RH), with additional placebo for the first 4 months (16 weeks). | Drug | 24-Week Regimen (Standard of Care Treatment) + Placebo for 16 weeks |
Primary outcome
Proportion of participants with an unfavourable efficacy outcome (treatment failure, recurrence or re-treatment for poor treatment response) through week 48 in the intention to treat population.
Time frame: From enrollment through to Week 48.
11 secondary outcomes
Death
Time frame: 72 weeks
Treatment-emergent adverse events
Time frame: 14 days after end of randomised treatment
Proportion of participants experiencing symptoms of interest during assigned treatment (tolerability)
Time frame: 14 days after end of randomised treatment
Proportion of participants temporarily discontinuing assigned treatment (tolerability)
Time frame: 14 days after end of randomised treatement
Proportion of participants permanently discontinuing assigned treatment (tolerability)
Time frame: 14 days after end of randomised treatment
Percentage of treatment doses taken (adherence)
Time frame: 48 weeks
Total Time on Treatment
Time frame: 72 weeks
Proportion of participants with acquired (post-baseline) drug resistance
Time frame: 72 weeks
Scores on 5-level EQ-5D questionnaire
Time frame: 72 weeks
Catastrophic costs and cost-effectiveness ratios, calculated using the adapted WHO patient costs survey
Time frame: 72 weeks
Respiratory disability measured by Medical Research Council (MRC) Dyspnea scale
Time frame: 72 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Aug 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Christopher Cousins, MBChB PhD principal investigator
St George's, University of London
Sean Wasserman, MBChB PhD principal investigator
St George's, University of London
John Eikelboom, MBBS FRCPC principal investigator
Population Health Research Institute, McMaster University
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Extra 600mg of Rifampicin in people with Pulmonary TB, run by Hamilton Health Sciences Corporation.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 12 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Sarah Karampatos, BASc, MSc (905-296-5795, sarah.karampatos@phri.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of participants with an unfavourable efficacy outcome (treatment failure, recurrence or re-treatment for poor treatment response) through week 48 in the intention to treat population. (time frame: From enrollment through to Week 48.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Aug 2025.