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

Hamilton Health Sciences (HHS)

Status and phase: Not yet enrolling; Phase 3

Conditions: Pulmonary TB

Treatments: Drug: Placebo; Drug: Extra 600mg of Rifampicin

Study type: Interventional

Funder types: Other

Identifiers

NCT07118696

18513

Details and patient eligibility

About

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.

Full 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.

Enrollment: 1,000 estimated patients

Sex: All

Ages: 12+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

---

1,000 participants in 2 patient groups, including a placebo group

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

Experimental group

Description:

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.

Treatment:

Drug: Extra 600mg of Rifampicin

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

Placebo Comparator group

Description:

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).

Treatment:

Drug: Placebo