Tuberculosis, PulmonaryPhase 3TriDoReNCT03862248
Novel Triple-dose Tuberculosis Retreatment Regimens: How to Overcome Resistance Without Creating More
A Phase 3 study testing 6EH³RZ, 6EHR³Z and 6EHRZLfx in people with Tuberculosis, Pulmonary, run by Institute of Tropical Medicine, Belgium at 1 site in Bangladesh.
Trial 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. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Tuberculosis, Pulmonary
- What is being tested?
- 6EH³RZ, 6EHR³Z and 6EHRZLfx
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteBangladesh
- Study dates
- 30 Sep 2019to 1 Oct 2022
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
Who cannot join
- Patients transferred to a health facility not supported by Damien Foundation will be excluded. This includes patients diagnosed with HIV/TB-coinfection.
Trial locations and contacts
1 site in 1 country.
About this study
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.
- Conditions
- Tuberculosis, Pulmonary
- Being tested
- 6EH³RZ, 6EHR³Z, 6EHRZLfx
- Medical subject headings
- Tuberculosis, Pulmonary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
6EH³RZDrug
New high-dose isoniazid retreatment regimen (6EH³RZ) - H 15mg/kg
6EHR³ZDrug
New high-dose rifampicin retreatment regimen (6EHR³Z) - R 30mg/kg
6EHRZLfxDrug
WHO levofloxacin-strengthened regimen (6EHRZLfx)
| Study group | Role | What they receive |
|---|---|---|
| High-Dose Isoniazid | Experimental | New high-dose isoniazid retreatment regimen (6EH³RZ) - H 15mg/kg Receives: Drug: 6EH³RZ |
| High-Dose Rifampicin | Experimental | New high-dose rifampicin retreatment regimen (6EHR³Z) - R 30mg/kg Receives: Drug: 6EHR³Z |
| World Health Organisation (WHO) regimen | Active comparator | WHO levofloxacin-strengthened regimen (6EHRZLfx) Receives: Drug: 6EHRZLfx |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 18 months (6-month treatment + 12-month follow-up period)
Secondary outcomes (9)
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
Measured: At screening (day 0)
Identify predictors of bacteriological effectiveness
Identify predictors (including treatment regimen, resistance profile, presence of cavities, the grading of the smear, …) of bacteriological effectiveness
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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
Measured: 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, …).
Measured: 18 months (6-month treatment + 12-month follow-up period)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Mar 2019
- Study start30 Sep 2019 (estimated)
- Primary completion1 Oct 2022 (estimated)
- Study completion1 Oct 2022 (estimated)
Why it stopped: Feasibility of the clinical trial could not be confirmed at the different sites.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Tuberculosis, PulmonaryStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Institute of Tropical Medicine, Belgium
- Sponsor type
- University, hospital or other
- Collaborators
- Damien Foundation
- Responsible party
- Sponsor
- Investigators
- Tom Decroo, MD, Principal investigator, Insitute of Tropical Medicine Antwerp
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03862248
- Sponsor's protocol ID
- TriDoRe
- Acronym
- TriDoRe
- Status last verified
- Jan 2020
- First submitted
- 4 Feb 2019
- Last updated
- 21 Jan 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Novel Triple-dose Tuberculosis Retreatment Regimens: How to Overcome Resistance Without Creating More
- ClinicalTrials.gov ID
- NCT03862248
- Acronym / sponsor ID
- TriDoRe / TriDoRe
- Conditions
- Tuberculosis, Pulmonary
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Feasibility of the clinical trial could not be confirmed at the different sites.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Institute of Tropical Medicine, BelgiumUniversity, hospital or other
- Collaborators
- Damien Foundation
- Study start
- 30 Sep 2019 (estimated)
- Primary completion
- 1 Oct 2022 (estimated)
- Study completion
- 1 Oct 2022 (estimated)
- First posted
- 5 Mar 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| High-Dose Isoniazid | Experimental | Drug: 6EH³RZNew high-dose isoniazid retreatment regimen (6EH³RZ) - H 15mg/kg |
| High-Dose Rifampicin | Experimental | Drug: 6EHR³ZNew high-dose rifampicin retreatment regimen (6EHR³Z) - R 30mg/kg |
| World Health Organisation (WHO) regimen | Active comparator | Drug: 6EHRZLfxWHO levofloxacin-strengthened regimen (6EHRZLfx) |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (1 listed)
- Patients transferred to a health facility not supported by Damien Foundation will be excluded. This includes patients diagnosed with HIV/TB-coinfection.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 6EH³RZNew high-dose isoniazid retreatment regimen (6EH³RZ) - H 15mg/kg | Drug | High-Dose Isoniazid |
| 6EHR³ZNew high-dose rifampicin retreatment regimen (6EHR³Z) - R 30mg/kg | Drug | High-Dose Rifampicin |
| 6EHRZLfxWHO levofloxacin-strengthened regimen (6EHRZLfx) | Drug | World Health Organisation (WHO) regimen |
Primary outcome
Bacteriological effectiveness (proportion of relapse-free cure excluding deaths and lost-to-follow-up)
Time frame: 18 months (6-month treatment + 12-month follow-up period)
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.
9 secondary outcomes
Frequency of resistance to the different drug components at screening.
Time frame: At screening (day 0)
Identify predictors of bacteriological effectiveness
Time frame: 18 months (6-month treatment + 12-month follow-up period)
Programmatic effectiveness (i.e proportion of participants with relapse-free cure)
Time frame: 18 months (6-month treatment + 12-month follow-up period)
Number of SAEs and study-specific adverse events of the different retreatment regimens
Time frame: up to month 6
Negative predictive value of two-week FDA
Time frame: 2 weeks after start of treatment
Proportion of participants relapse-free cure
Time frame: 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
Time frame: 18 months (6-month treatment + 12-month follow-up period)
Proportion of participants with acquired resistance
Time frame: 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, …)
Time frame: 18 months (6-month treatment + 12-month follow-up period)
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Jan 2020.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Tom Decroo, MD principal investigator
Insitute of Tropical Medicine Antwerp
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing 6EH³RZ, 6EHR³Z and 6EHRZLfx in people with Tuberculosis, Pulmonary, run by Institute of Tropical Medicine, Belgium at 1 site in Bangladesh.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 21 Jan 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Bangladesh. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Bacteriological effectiveness (proportion of relapse-free cure excluding deaths and lost-to-follow-up) (time frame: 18 months (6-month treatment + 12-month follow-up period)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Jan 2020.