NCT04260477

Novel Triple-dose Tuberculosis Retreatment Regimen

Novel Triple-dose Tuberculosis Retreatment Regimen: How to Overcome Resistance Without Creating More in Niger

• Status: Recruiting
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 370 (estimated)
• Sponsor: Institute of Tropical Medicine, Belgium · Academic / Other
• Sex: All
• Age: —
• Healthy volunteers: Not accepted

Summary

To determine if a high-dose first-line regimen is non-inferior (non-inferiority margin 10%) in terms of safety to the same regimen at regular dosing, in previously treated patients with rifampicin-susceptible recurrent Tuberculosis (TB).

Detailed description

Stage 1: This is a pragmatic open-label multi-stage randomized clinical trial. Potential participants will be screened and enrolled in Damien Foundation (DF) clinics participating in the trial. First we will perform a two-arm study with 6EHRZ as control arm and 6EH³R³Z as intervention arm. If at interim analysis the intervention arm is not considered to be non-inferior to the control arm, the intervention stops and enrolment will continue in a an adapted intervention arm and the control arm (6EHRZ). Otherwise, enrolment continues to 6EHRZ and 6EH³R³Z. Observational study (stage 2): The DSMB members agreed due to safety concerns to continuing the study as a cohort with only the control arm. The control regimen will remain the same (6EHRZ). As per routine practice, during treatment patients are in daily contact with the direct observed therapy (DOT) supervisor and minimally monthly clinic visits are scheduled for monitoring of safety and treatment response. Additionally, liver function tests will be performed at fixed intervals during treatment. Six month and one year after treatment completion or cure the patient will be checked for relapse with systematic sputum acid-fast bacilli (AFB)-microscopy and TB culture.

Conditions

• Multidrug-resistant Tuberculosis
• Pulmonary Tuberculosis
• Tuberculosis
• Resistance to Tuberculostatic Drugs

Interventions

Type	Name	Description
DRUG	6EH³R³Z	A triple dose is defined as the triple of the routine dose used for a specific WHO weight band. Hence, the mg/kg within a weigh-band varies, as is the case in routine practice. Dosing takings into consideration the fixed dose combination (FDC) tablets (one tablet: 150 mg R + 75 mg H + 400 mg Z + 275mg E). Dosage relies on tables with dosage by weight-bands used by WHO for the Cat. 1 regimen. The dosage used for the intensive phase of the Cat. 1 regimen applies for the whole treatment duration. A double dose of H and R is added to the recommended normal dose for adults (WHO,2003)
DRUG	6EHRZ	Recommended normal dose adults (WHO, 2003) * H: 5 (4-6) mg/kg/day * R: 10 (8-12) mg/kg/day * Z: 25 (20-30)mg/kg/day * E: 15 (15-18)mg/kg/day

Timeline

• Start date: 2021-03-01
• Primary completion: 2025-06-01
• Completion: 2025-09-01
• First posted: 2020-02-07
• Last updated: 2025-04-13

Locations

1 site across 1 country: Niger