Evaluating a Shorter, Rifampicin-Based Treatment for People With Less Severe Tuberculosis Disease

Not Applicable

Not yet recruiting

• Conditions: Pulmonary TB
• Interventions: Drug: Extra 600mg of Rifampicin; Drug: Placebo

• Registration Number: NCT07118696
• Lead Sponsor: Hamilton Health Sciences Corporation

Brief 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.

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 Timeline

• Status Verified: 2025-07
• Study First Submitted: 2025-07-25
• Study First Submitted QC: 2025-08-07
• Last Update Submitted: 2025-08-07
• Study First Posted: 2025-08-12
• Last Update Posted: 2025-08-12
• Study Start: 2026-02-01
• Primary Completion: 2029-01-31
• Study Completion: 2030-01-31

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 1000

Inclusion Criteria

1. Aged 12 years and over
2. Clinical and/or radiological evidence of pulmonary TB
3. At least one sputum specimen positive for M. tuberculosis by Xpert MTB/RIF or Ultra within 30 days of screening confirming rifampicin-sensitive TB
4. 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)
5. Documentation of HIV status from a validated test performed within 30 days of screening or known to be HIV-positive
6. Well enough to be treated as an outpatient

Exclusion Criteria

1. Received more than 7 days treatment for index TB episode

2. Previous treatment for active TB disease in past 12 months

3. M. tuberculosis with known resistance to rifampicin or isoniazid

4. Weight < 30 kg at screening

5. 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)

6. 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)

7. For participants living with HIV:

   • Urinary lipoarabinomannan test positive at screening
   • Requires protease inhibitor-based antiretroviral therapy, and/or long acting antiretrovirals cabotegravir/rilpivirine

8. 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

9. Clinical evidence of acute hepatitis or advanced chronic liver disease (e.g. jaundice, signs of portal hypertension)

10. Known end stage renal failure

11. Active malignancy not in remission or had systemic chemotherapy within 2 years (except for non-melanomatous skin cancer)

12. Contraindication to study medications because of known allergy or intolerance or unavoidable drug-drug interaction

13. Other medical conditions, that, in the investigator's judgment, make study participation not in the individual's best interest

14. Inability to attend follow up visits

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
16-Week Regimen (Standard of Care Treatment + 600 mg of Rifampicin daily)	Extra 600mg of Rifampicin	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.
24-Week Regimen (Standard of Care Treatment) + Placebo for 16 weeks	Placebo	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).

Primary Outcome Measures

Name	Time	Method
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.	From enrollment through to Week 48.

Secondary Outcome Measures

Name	Time	Method
Death	72 weeks
Treatment-emergent adverse events	14 days after end of randomised treatment	Any adverse event leading to premature, permanent discontinuation of a study drug.; Treatment-related adverse events of special interest. Treatment-related SAEs.
Proportion of participants experiencing symptoms of interest during assigned treatment (tolerability)	14 days after end of randomised treatment	Proportion of participants experiencing symptoms of interest during assigned treatment (tolerability)
Proportion of participants temporarily discontinuing assigned treatment (tolerability)	14 days after end of randomised treatement	Proportion of participants temporarily discontinuing assigned treatment (tolerability)
Proportion of participants permanently discontinuing assigned treatment (tolerability)	14 days after end of randomised treatment	Proportion of participants permanently discontinuing assigned treatment (tolerability)
Percentage of treatment doses taken (adherence)	48 weeks	Percentage of treatment doses taken (adherence)
Total Time on Treatment	72 weeks	Total Time on Treatment
Proportion of participants with acquired (post-baseline) drug resistance	72 weeks	Proportion of participants with acquired (post-baseline) drug resistance
Scores on 5-level EQ-5D questionnaire	72 weeks	Scores on 5-level EQ-5D questionnaire
Catastrophic costs and cost-effectiveness ratios, calculated using the adapted WHO patient costs survey	72 weeks	Catastrophic costs and cost-effectiveness ratios, calculated using the adapted WHO patient costs survey
Respiratory disability measured by Medical Research Council (MRC) Dyspnea scale	72 weeks	Respiratory disability measured by Medical Research Council (MRC) Dyspnea scale