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

NCT ID: NCT07118696

Last Updated: 2025-08-12

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 1000 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2026-02-01
• Study Completion Date: 2030-01-31

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.

Conditions

Pulmonary TB

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

16-Week Regimen (Standard of Care Treatment + 600 mg of Rifampicin daily)

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.

Group Type: EXPERIMENTAL

Extra 600mg of Rifampicin

Intervention Type: DRUG

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.

24-Week Regimen (Standard of Care Treatment) + Placebo for 16 weeks

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).

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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).

Interventions

Extra 600mg of Rifampicin

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.

Intervention Type: DRUG

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).

Intervention Type: DRUG

Other Intervention Names

Experimental; Control

Eligibility Criteria

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

• Minimum Eligible Age: 12 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

St George's, University of London

OTHER

Sponsor Role: collaborator

McMaster University

OTHER

Sponsor Role: collaborator

Hamilton Health Sciences Corporation

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Christopher Cousins, MBChB PhD

Role: PRINCIPAL_INVESTIGATOR

St George's, University of London

Sean Wasserman, MBChB PhD

Role: PRINCIPAL_INVESTIGATOR

St George's, University of London

John Eikelboom, MBBS FRCPC

Role: PRINCIPAL_INVESTIGATOR

Population Health Research Institute, McMaster University

Central Contacts

Sarah Karampatos, BASc, MSc

Role: CONTACT

sarah.karampatos@phri.ca

905-296-5795

Steven Agapay, BSc

Role: CONTACT

steve.agapay@phri.ca

905-296-5764

Other Identifiers

18513

Identifier Type: -

Identifier Source: org_study_id