Novel Triple-dose Tuberculosis Retreatment Regimen
Tri-Do-Re
1 other identifier
interventional
370
1 country
1
Brief 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).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3
Started Mar 2021
Typical duration for phase_3
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
February 3, 2020
CompletedFirst Posted
Study publicly available on registry
February 7, 2020
CompletedStudy Start
First participant enrolled
March 1, 2021
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 1, 2025
CompletedStudy Completion
Last participant's last visit for all outcomes
September 1, 2025
CompletedApril 13, 2025
April 1, 2025
4.3 years
February 3, 2020
April 10, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (3)
STAGE 1:number of patients with any grade 3-5 Adverse Event (AE) during treatment, assessed as probably or definitely related to TB treatment
18 months
STAGE 2: Describe bacterial effectiveness
for stage 2 participants of the trial
18 months
STAGE 2: Describe acquired resistance
for stage 2 participants of the trial
18 months
Secondary Outcomes (17)
STAGE 1: number of previously treated patients with H-monoresistance and H-polyresistance, rifampicin (RMP) resistance missed by Xpert Mycobacterium tuberculosis (MTB)/rifampicin (RIF)
18 months
STAGE 1: Programmatical effectiveness:number of participants with treatment success divided by number of participants with failure, death, or Lost to follow-up (LTFU)
6 months, 18 months
STAGE 1: Clinical effectiveness: number of participants with treatment success, divided by number of participants with failure or death
6 months, 18 months
STAGE 1:Bacteriological effectiveness : number of participants with treatment success, divided by number of participants with failure
6 months, 18 months
STAGE 2:Bacteriological effectiveness : number of participants with treatment success, divided by number of participants with failure
6 months, 18 months
- +12 more secondary outcomes
Study Arms (2)
6EH³R3Z
EXPERIMENTAL(Rifampicin (R)/ Isoniazid (H) / Pyrazinamide (Z)/Ethambutol (E)) 6-month high-dose treatment; New high-dose isoniazid / high-dose rifampicin retreatment regimen (6EH³R3Z) - that includes triple-dose rifampicin (R3; 30 mg/kg), and triple-dose isoniazid (H3; 15 mg/kg), complemented with pyrazinamide (Z) and ethambutol (E).
6EHRZ
ACTIVE COMPARATORStandard of care: 6-month 6RHZE regimen with dose combination tablets (one tablet: 150 mg R + 75 mg H + 400 mg Z + 275mg E)
Interventions
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)
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
Eligibility Criteria
You may qualify if:
- All newly registered patients with smear-positive recurrent pulmonary TB
- Adults as well as children (no age limit)
- Able and willing to provide written informed consent
- Added for stage 2: lives within 5 km of a health facility with a medical doctor
You may not qualify if:
- All patients with TB initially resistant to rifampicin on Xpert MTB/RIF testing
- Patients transferred to a health facility not supported by the Damien Foundation
- Patients previously enrolled in the trial, and with another episode of rifampicin-susceptible TB during the study period
- Those with grade III elevation of liver function tests at baseline, or with clinically active liver disease at screening
- Pregnant or breastfeeding woman
- HIV co-infected patients requiring treatment with a protease inhibitor
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Institute of Tropical Medicine, Belgiumlead
- Damien Foundationcollaborator
Study Sites (1)
Damien Foundation
Niamey, Niger
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Sani Kadri
Ministry of Health, Niger
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Masking Details
- Providers in the TB clinics and lab technicians in the Niger clinics and labs will not be blinded to the prescribed regimen. However, lab technicians working in the Institute of Tropical Medicine (ITM) lab will be blinded to the prescribed regimen. Also the statistician will be blinded to the prescribed regimen until the first interim analysis is completed.
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
February 3, 2020
First Posted
February 7, 2020
Study Start
March 1, 2021
Primary Completion
June 1, 2025
Study Completion
September 1, 2025
Last Updated
April 13, 2025
Record last verified: 2025-04
Data Sharing
- IPD Sharing
- Will not share