Novel Triple-dose Tuberculosis Retreatment Regimen
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: 6EH³R³Z, 6EHRZ.
- Who it may be relevant to
- Registry conditions: Multidrug-resistant Tuberculosis, Pulmonary Tuberculosis, Tuberculosis, Resistance to Tuberculostatic Drugs. Basic parameters: No limits · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- Niger
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
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Official title
Novel Triple-dose Tuberculosis Retreatment Regimen: How to Overcome Resistance Without Creating More in Niger
Overview
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.
Interventions
- 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. - 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
Primary outcome measures
- STAGE 1:number of patients with any grade 3-5 Adverse Event (AE) during treatment, assessed as probably or definitely related to TB treatment [Time frame: 18 months]
- STAGE 2: Describe bacterial effectiveness [Time frame: 18 months]
- STAGE 2: Describe acquired resistance [Time frame: 18 months]
Secondary outcome measures (12)
- STAGE 1: number of previously treated patients with H-monoresistance and H-polyresistance, rifampicin (RMP) resistance missed by Xpert Mycobacterium tuberculosis (MTB)/rifampicin (RIF) [Time frame: 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) [Time frame: 6 months, 18 months]
- STAGE 1: Clinical effectiveness: number of participants with treatment success, divided by number of participants with failure or death [Time frame: 6 months, 18 months]
- STAGE 1:Bacteriological effectiveness : number of participants with treatment success, divided by number of participants with failure [Time frame: 6 months, 18 months]
- STAGE 2:Bacteriological effectiveness : number of participants with treatment success, divided by number of participants with failure [Time frame: 6 months, 18 months]
- STAGE 2: number of participants with acquired resistance, to Isoniazid (INH) and/or RMP [Time frame: 6 months, 18 months]
- number of participants with stable (without reversion) SSM conversion [Time frame: 2 months]
- STAGE 1: number of participants with drug-induced hepatotoxicity [Time frame: 18 months]
- STAGE 1:number of participants with any TB treatment change due to drug-induced hepatoxicity [Time frame: 18 months]
- STAGE 1:number of participants with any TB treatment change due to AE [Time frame: 18 months]
- STAGE 1:number of participants with any grade 3-5 AE [Time frame: 18 months]
- STAGE 1:number of participants with any Serious Adverse Event (SAE) [Time frame: 18 months]
Eligibility criteria
Inclusion criteria
- 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
Exclusion criteria
- 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
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Allocation
- Randomized
- Model
- Parallel assignment
- Masking
- Open label
- Primary purpose
- Treatment
Study locations
Niger · 1 center
- Damien Foundation — Niamey
Identifiers
NCT: NCT04260477 · ITM202001