Clinical trial NCT03862248: Novel Triple-dose Tuberculosis Retreatment Regimens: How to Overcome Resistance Without Creating More
Official title: Novel Triple-dose Tuberculosis Retreatment Regimens: How to Overcome Resistance Without Creating More
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE3
Conditions: Tuberculosis, Pulmonary
Lead sponsor: Institute of Tropical Medicine, Belgium
Sponsor class: OTHER
Collaborators: name: Damien Foundation
First posted: 2019-03-05
Enrollment: 0
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


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

Exclusion Criteria:

* Patients transferred to a health facility not supported by Damien Foundation will be excluded. This includes patients diagnosed with HIV/TB-coinfection.

Primary outcomes:
measure: Bacteriological effectiveness (proportion of relapse-free cure excluding deaths and lost-to-follow-up)
timeFrame: 18 months (6-month treatment + 12-month follow-up period)
Secondary outcomes:
measure: Frequency of resistance to the different drug components at screening.
timeFrame: At screening (day 0)
measure: Identify predictors of bacteriological effectiveness
timeFrame: 18 months (6-month treatment + 12-month follow-up period)
measure: Programmatic effectiveness (i.e proportion of participants with relapse-free cure)
timeFrame: 18 months (6-month treatment + 12-month follow-up period)
measure: Number of SAEs and study-specific adverse events of the different retreatment regimens
timeFrame: up to month 6
measure: Negative predictive value of two-week FDA
timeFrame: 2 weeks after start of treatment
measure: Proportion of participants relapse-free cure
timeFrame: 18 months (6-month treatment + 12-month follow-up period)
measure: 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
timeFrame: 18 months (6-month treatment + 12-month follow-up period)
measure: Proportion of participants with acquired resistance
timeFrame: 18 months (6-month treatment + 12-month follow-up period)
measure: Identify predictors of programmatic effectiveness (including treatment regimen, resistance profile, presence of cavities, the grading of the smear, …)
timeFrame: 18 months (6-month treatment + 12-month follow-up period)
Other outcomes:
Locations:
city: Dhaka
country: Bangladesh
facility: Damien Foundation
Study officials:
affiliation: Insitute of Tropical Medicine Antwerp
name: Tom Decroo, MD
role: PRINCIPAL_INVESTIGATOR
References: