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

NCT07118696 | Not Yet Recruiting Phase 3

• 1 other identifier: 18513
• Study Type: interventional
• Target: 1,000
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Pulmonary TB

Keywords

Rifampicin; Treatment Shortening

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (11)

• Death

  72 weeks

• Treatment-emergent adverse events

  14 days after end of randomised treatment

• Proportion of participants experiencing symptoms of interest during assigned treatment (tolerability)

  14 days after end of randomised treatment

• Proportion of participants temporarily discontinuing assigned treatment (tolerability)

  14 days after end of randomised treatement

• Proportion of participants permanently discontinuing assigned treatment (tolerability)

  14 days after end of randomised treatment

Study Arms (2)

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.

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).

Drug: Placebo

Interventions

Extra 600mg of Rifampicin 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.

Also known as: Experimental

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

Placebo 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).

Also known as: Control

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

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)
• 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

Sponsors & Collaborators

• Hamilton Health Sciences Corporation: lead
• St George's, University of London: collaborator
• McMaster University: collaborator

MeSH Terms

Conditions

Tuberculosis, Pulmonary

Interventions

Rifampin

Condition Hierarchy (Ancestors)

Tuberculosis; Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Rifamycins; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds

Study Officials

• Christopher Cousins, MBChB PhD

  St George's, University of London

  PRINCIPAL INVESTIGATOR

• Sean Wasserman, MBChB PhD

  St George's, University of London

  PRINCIPAL INVESTIGATOR

• John Eikelboom, MBBS FRCPC

  Population Health Research Institute, McMaster University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sarah Karampatos, BASc, MSc

CONTACT

905-296-5795; sarah.karampatos@phri.ca

Steven Agapay, BSc

CONTACT

905-296-5764; steve.agapay@phri.ca

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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).

Study Record Dates

• First Submitted: July 25, 2025
• First Posted: August 12, 2025
• Study Start: February 1, 2026
• Primary Completion (Estimated): January 31, 2029
• Study Completion (Estimated): January 31, 2030
• Last Updated: August 12, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share