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Feasibility of the clinical trial could not be confirmed at the different sites.
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| Name | Class |
|---|---|
| Damien Foundation | OTHER |
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Drug-resistance is a major challenge for tuberculosis (TB) care programs. The new WHO guideline recommends adding levofloxacin in previously treated patients with isoniazid-resistant rifampicin-susceptible TB. The investigators believe that such a retreatment regimen may result in acquired resistance to fluoroquinolone, the core drug of multidrug-resistant TB (MDR-TB) regimen, and thus threaten the effectiveness of the fluoroquinolone-based MDR-TB treatment regimen. Therefore the investigators propose to study if regimens strengthened by using high-dose first-line drugs, either a triple dose of isoniazid or a triple dose of rifampicin, are non-inferior to the WHO recommended levofloxacin-strengthened regimen. If one of both high-dose regimens would be non-inferior, it could replace the levofloxacin-strengthened regimen.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| High-Dose Isoniazid | Experimental | New high-dose isoniazid retreatment regimen (6EH³RZ) - H 15mg/kg |
|
| High-Dose Rifampicin | Experimental | New high-dose rifampicin retreatment regimen (6EHR³Z) - R 30mg/kg |
|
| World Health Organisation (WHO) regimen | Active Comparator | WHO levofloxacin-strengthened regimen (6EHRZLfx) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 6EH³RZ | Drug | New high-dose isoniazid retreatment regimen (6EH³RZ) - H 15mg/kg |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Bacteriological effectiveness (proportion of relapse-free cure excluding deaths and lost-to-follow-up) | To study if the bacteriological effectiveness of two high-dose regimens is non-inferior to the WHO recommended levofloxacin-strengthened regimen in patients with rifampicin-susceptible recurrent TB. Relapse-free cure is based on sputum smear and culture-result. | 18 months (6-month treatment + 12-month follow-up period) |
| Measure | Description | Time Frame |
|---|---|---|
| Frequency of resistance to the different drug components at screening. | Determine the initial resistance profile to the different drug components (Isoniazid, Rifampicin, Pyrazinamide and Levofloxacin) for the entire cohort of patients with recurrent TB | At screening (day 0) |
| Identify predictors of bacteriological effectiveness |
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Inclusion Criteria:
Exclusion Criteria:
participant eligibility is based on self-representation of gender identity
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| Name | Affiliation | Role |
|---|---|---|
| Tom Decroo, MD | Insitute of Tropical Medicine Antwerp | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Damien Foundation | Dhaka | Bangladesh |
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| ID | Term |
|---|---|
| D014397 | Tuberculosis, Pulmonary |
| ID | Term |
|---|---|
| D014376 | Tuberculosis |
| D009164 | Mycobacterium Infections |
| D000193 | Actinomycetales Infections |
| D016908 | Gram-Positive Bacterial Infections |
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| 6EHR³Z |
| Drug |
New high-dose rifampicin retreatment regimen (6EHR³Z) - R 30mg/kg |
|
| 6EHRZLfx | Drug | WHO levofloxacin-strengthened regimen (6EHRZLfx) |
|
Identify predictors (including treatment regimen, resistance profile, presence of cavities, the grading of the smear, …) of bacteriological effectiveness |
| 18 months (6-month treatment + 12-month follow-up period) |
| Programmatic effectiveness (i.e proportion of participants with relapse-free cure) | Compare the programmatic effectiveness of the 3 different regimens. Relapse-free cure is based on sputum smear and culture-result. | 18 months (6-month treatment + 12-month follow-up period) |
| Number of SAEs and study-specific adverse events of the different retreatment regimens | Compare the safety (SAEs and study-specific adverse events ) of the different retreatment regimens. | up to month 6 |
| Negative predictive value of two-week FDA | Evaluate a novel application of fluorescein diacetate vital staining fluorescence microscopy (FDA) at 0 and 2 weeks of treatment, to estimate its utility as screening test for initial resistance to rifampicin, and identify predictors for FDA reduction at 2 weeks. The negative predictive value of two-week FDA showing no lack of 10-fold reduction of viable bacilli at two weeks. | 2 weeks after start of treatment |
| Proportion of participants relapse-free cure | To estimate the proportion of relapse-free cure among patients with FDA conversion to zero at 2 weeks, by regimen.The proportion (95% confidence interval) relapse-free cure among those who converted on the two-week FDA, by regimen. | 18 months (6-month treatment + 12-month follow-up period) |
| Difference (95% confidence interval) in bacteriological effectiveness (susceptible to both rifampicin and isoniazid vs heteroresistance to rifampicin and/or isoniazid).(heteroresistance), by regimen studied in the trial | Estimate the clinical relevance of different proportions of mutant subpopulations (heteroresistance), by regimen studied in the trial. | 18 months (6-month treatment + 12-month follow-up period) |
| Proportion of participants with acquired resistance | proportion of participants with acquired resistance, by treatment regimen | 18 months (6-month treatment + 12-month follow-up period) |
| Identify predictors of programmatic effectiveness (including treatment regimen, resistance profile, presence of cavities, the grading of the smear, …) | Identify predictors (including treatment regimen, resistance profile, presence of cavities, the grading of the smear, …). | 18 months (6-month treatment + 12-month follow-up period) |
| D001424 | Bacterial Infections |
| D001423 | Bacterial Infections and Mycoses |
| D007239 | Infections |
| D012141 | Respiratory Tract Infections |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |