Tuberculosis, PulmonaryPhase 3OneRIFNCT02153528
Optimization of the TB Treatment Regimen Cascade
A Phase 3 study testing double rimfampicin and Standard TB treatment in people with Tuberculosis, Pulmonary, run by Damien Foundation at 1 site in Bangladesh.
Trial summary
Hypothesis: Double dose rifampicin together with earlier monitoring of sputum conversion using vital staining reduces unfavorable outcome of Cat. 1 first-line TB treatment without excess serious toxicity, and allows early switch to specific treatment of MDR-TB without using Cat. Read more about this study
- Who is it for?
- Ages 15 years and older
- Conditions the study is for
- Tuberculosis, Pulmonary
- What is being tested?
- double rimfampicin and Standard TB treatment
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 701 participants
- Where
- 1 siteBangladesh
- Study dates
- Nov 2014to 1 Aug 2017
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 15 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Diagnosed with smear-positive pulmonary TB
- 15 years or older
- Able and willing to provide written informed consent
Who cannot join
- contacts of MDR-TB patients and other MDR-TB suspects diagnosed with resistance on rapid DST for rifampicin performed prior to start of treatment according to NTP guidelines
- smear-negative pulmonary and extra-pulmonary TB cases
- patients in need of hospitalization because of very bad general condition or complications
- patients with clinically active liver disease, for the study defined as jaundice confirmed by a local Medical Officer (Government)
- any known HIV-positive patient (although none are expected)
- any patient with known hepatitis B or C infection
- pregnant women; in addition, patients in the intervention arm who become pregnant during treatment will be switched to the control arm
Trial locations and contacts
1 site in 1 country.
Bangladesh1 site
Damien Foundation Bangladesh TB project in Greater Mymensingh district (8 selected clinics)
Dhaka, Greater Mymensingh District
About this study
- Hypothesis: Double dose rifampicin together with earlier monitoring of sputum conversion using vital staining reduces unfavorable outcome of Cat. 1 first-line TB treatment without excess serious toxicity, and allows early switch to specific treatment of MDR-TB without using Cat. 2 retreatment regimen
- General study design: This open label, randomised clinical trial is intended as a pilot study on the efficacy and safety of high-dose rifampicin and feasibility and added value of auramine and/or FDA vital staining sputum smear after 2 weeks of intensive treatment phase. If this proof-of-concept study provides substantial indication of benefit without indication of excess toxicity, the data from the study will be used to design a larger scale, cluster-randomized study. The aim of this cluster randomised study would be to provide definite proof of the benefit of the intervention on adverse treatment outcomes and lack of excess toxicity associated with high dose rifampicin. In addition, the cluster-randomized study would provide a more precise assessment of the suppression and prevention of (acquired) resistance endpoints.
An interim analysis is thus planned at the time the last recruited patient finishes treatment, i.e. about 9 months after the end of recruitment. It will focus on assessment of drug toxicity versus suggested benefits of the intervention. This analysis will be primarily performed for the go/no-go decision and design considerations for the cluster-randomized trial. The decision on proceeding to the cluster randomized study will be based on the absence of excess toxicity, a trend toward a reduction of unfavourable outcomes (excluding relapse), and possible favourable effects on initially present low-resistance mutations / mutations acquired during treatment. It will also allow to adapt the design of the larger study particularly regarding the algorithm for resistance screening, and whether or not treatment shortening could be justified with rapid initial conversion.
- Conditions
- Tuberculosis, Pulmonary
- Being tested
- double rimfampicin, Standard TB treatment
- Keywords
- Bangladesh, Rimfapicin
- Medical subject headings
- Tuberculosis, Pulmonary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
double rimfampicinDrug
Also called Intervention arm
Compared to standard regimen dosing of rifampicin is doubled, while standard dose isoniazid, pyrazinamide and ethambutol are maintained
Standard TB treatmentDrug
Also called Control arm
Standard regimen for TB treatment according to guidelines of the International Union against Tuberculosis and Lung Disease
| Study group | Role | What they receive |
|---|---|---|
| Standard TB treatment | Active comparator | Standard regimen for TB treatment according to guidelines of the International Union against Tuberculosis and Lung Disease Receives: Drug: Standard TB treatment |
| double rimfampicin | Experimental | 2HREZ/4HR Cat. 1, modified by using double dose rifampicin throughout Receives: Drug: double rimfampicin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Tuberculose Treatment Outcome
Following current WHO guidelines, an adverse treatment outcome is defined as any occurrence of the following:
- Relapse: Cured previously from TB or completed treatment for TB and now having bacteriologically positive sputum for TB (at 12 months follow-up or at an earlier time point)
- Default: The patient whose treatment was interrupted for ≥ 2 consecutive months.
- Failure: Sputum positive for TB at 5 months or later during treatment. In line with current WHO recommendations, patients detected with MDR-TB or rifampicin resistance before this or another outcome applies and switched to the MDR-TB regimen will be excluded from the outcome analysis.18 Failure will also be declared if the regimen has to be changed for at least 2 drugs due to adverse events.
- Death: All-cause mortality between case registration and end of TB treatment (related or not to TB or TB treatment)
Measured: 12 months after end of treatment
Number of Participants Who Develop Liver Toxicity
Grade 3-4 Liver Toxicity following NIH common toxicity criteria (CTC), including transaminase increases to >5-20 ULN (grade 3), or > 20 ULN (grade 4)
Measured: until month eight
Secondary outcomes (7)
High-level Rifampicin Resistant TB Adverse Treatment Outcomes
To assess whether the study regimen also cures high-level rifampicin resistant TB. Adverse treatment outcomes will be described and compared among treatment groups in subgroups defined by initial rifampicin resistance mutations (performed in all patients) detected.
Measured: 12 months after end of TB treatment
Number of Initial Resistant TB Cases Who Switched to MDR-TB Treatment or Were Cured
To assess the effectiveness of FDA vital staining versus fever screening for early switch of non-responding rifampicin resistant TB to MDR-TB treatment
Measured: at two weeks of treatment
the Negative Predictive Value of Conversion at 2 Weeks for Relapse.
The Negative Predictive value (and 95% CI) of conversion in the intervention arm will be estimated as the % of relapses among those with a minimum 1 log decline in the number of AFB, or who are already negative or only scanty positive on AFB smear (auramine or FDA).
Measured: at 2 weeks of treatment
Proportion of Acquired Rifampicin Resistance Among Failures and Relapses
number of failure / relapse cases without mutation detected at diagnosis as the denominator and comparing intervention and control arms.
Measured: 12 months after end of TB treatment
Area Under the Curve of Auramine Resp. FDA at 2 Weeks to Predict Adverse Treatment Outcome at 1 Year After Treatment Completion
Area under the ROC curve (AUC) to predict adverse treatment outcome. The X-axis represents the 1-specificity, the Y-axis represents sensitivity. The AUC is estimated with 95% confidence interval.
Measured: Auramine/FDA at 2 weeks and adverse treatment outcome 1 year after treatment completion
Weight Gain
Weight gain from baseline until end-of-treatment comparison between both treatment arms.
Measured: until end of treatment (month eight)
Fever Resolution
Comparison of fever resolution after 2 weeks of treatment between both treatment arms.
Measured: after 2 weeks of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Jun 2014 (estimated)
- Study startNov 2014
- Primary completion1 Aug 2017
- Study completion1 Aug 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- 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
- 701 participants (actual)
Sponsor and investigators
- Lead sponsor
- Damien Foundation
- Sponsor type
- University, hospital or other
- Collaborators
- National TB control Programme Bangladesh, Institute of Tropical Medicine, Belgium
- Responsible party
- Sponsor
- Investigators
- Aung Kya Jai Maug, MD, Principal investigator, Damien Foundation Bangladesh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02153528
- Sponsor's protocol ID
- OneRIF
- Acronym
- OneRIF
- Status last verified
- Feb 2020
- First submitted
- 26 May 2014
- Last updated
- 13 Feb 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 13 Feb 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Optimization of the TB Treatment Regimen Cascade
- ClinicalTrials.gov ID
- NCT02153528
- Acronym / sponsor ID
- OneRIF / OneRIF
- Conditions
- Tuberculosis, Pulmonary
- Keywords
- Bangladesh, Rimfapicin
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 701 participants (actual)
- Lead sponsor
- Damien FoundationUniversity, hospital or other
- Collaborators
- National TB control Programme Bangladesh, Institute of Tropical Medicine, Belgium
- Study start
- Nov 2014
- Primary completion
- 1 Aug 2017 (actual)
- Study completion
- 1 Aug 2017 (actual)
- First posted
- 3 Jun 2014 (estimated)
- Results
- Posted 13 Feb 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
- Hypothesis: Double dose rifampicin together with earlier monitoring of sputum conversion using vital staining reduces unfavorable outcome of Cat. 1 first-line TB treatment without excess serious toxicity, and allows early switch to specific treatment of MDR-TB without using Cat. 2 retreatment regimen
- General study design: This open label, randomised clinical trial is intended as a pilot study on the efficacy and safety of high-dose rifampicin and feasibility and added value of auramine and/or FDA vital staining sputum smear after 2 weeks of intensive treatment phase. If this proof-of-concept study provides substantial indication of benefit without indication of excess toxicity, the data from the study will be used to design a larger scale, cluster-randomized study. The aim of this cluster randomised study would be to provide definite proof of the benefit of the intervention on adverse treatment outcomes and lack of excess toxicity associated with high dose rifampicin. In addition, the cluster-randomized study would provide a more precise assessment of the suppression and prevention of (acquired) resistance endpoints.
An interim analysis is thus planned at the time the last recruited patient finishes treatment, i.e. about 9 months after the end of recruitment. It will focus on assessment of drug toxicity versus suggested benefits of the intervention. This analysis will be primarily performed for the go/no-go decision and design considerations for the cluster-randomized trial. The decision on proceeding to the cluster randomized study will be based on the absence of excess toxicity, a trend toward a reduction of unfavourable outcomes (excluding relapse), and possible favourable effects on initially present low-resistance mutations / mutations acquired during treatment. It will also allow to adapt the design of the larger study particularly regarding the algorithm for resistance screening, and whether or not treatment shortening could be justified with rapid initial conversion.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Standard TB treatment | Active comparator | Drug: Standard TB treatmentStandard regimen for TB treatment according to guidelines of the International Union against Tuberculosis and Lung Disease |
| double rimfampicin | Experimental | Drug: double rimfampicin2HREZ/4HR Cat. 1, modified by using double dose rifampicin throughout |
Who may qualify
- Ages
- 15 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (3 listed)
- Diagnosed with smear-positive pulmonary TB
- 15 years or older
- Able and willing to provide written informed consent
Key exclusion criteria (7 listed)
- contacts of MDR-TB patients and other MDR-TB suspects diagnosed with resistance on rapid DST for rifampicin performed prior to start of treatment according to NTP guidelines
- smear-negative pulmonary and extra-pulmonary TB cases
- patients in need of hospitalization because of very bad general condition or complications
- patients with clinically active liver disease, for the study defined as jaundice confirmed by a local Medical Officer (Government)
- any known HIV-positive patient (although none are expected)
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 |
|---|---|---|
| double rimfampicinAlso: Intervention armCompared to standard regimen dosing of rifampicin is doubled, while standard dose isoniazid, pyrazinamide and ethambutol are maintained | Drug | double rimfampicin |
| Standard TB treatmentAlso: Control armStandard regimen for TB treatment according to guidelines of the International Union against Tuberculosis and Lung Disease | Drug | Standard TB treatment |
Primary outcome
Tuberculose Treatment Outcome
Time frame: 12 months after end of treatment
Following current WHO guidelines, an adverse treatment outcome is defined as any occurrence of the following: * Relapse: Cured previously from TB or completed treatment for TB and now having bacteriologically positive sputum for TB (at 12 months follow-up or at an earlier time point) * Default: The patient whose treatment was interrupted for ≥ 2 consecutive months. * Failure: Sputum positive for TB at 5 months or later during treatment. In line with current WHO recommendations, patients detected with MDR-TB or rifampicin resistance before this or another outcome applies and switched to the MDR-TB regimen will be excluded from the outcome analysis.18 Failure will also be declared if the regimen has to be changed for at least 2 drugs due to adverse events. * Death: All-cause mortality between case registration and end of TB treatment (related or not to TB or TB treatment)
Number of Participants Who Develop Liver Toxicity
Time frame: until month eight
Grade 3-4 Liver Toxicity following NIH common toxicity criteria (CTC), including transaminase increases to >5-20 ULN (grade 3), or > 20 ULN (grade 4)
7 secondary outcomes
High-level Rifampicin Resistant TB Adverse Treatment Outcomes
Time frame: 12 months after end of TB treatment
Number of Initial Resistant TB Cases Who Switched to MDR-TB Treatment or Were Cured
Time frame: at two weeks of treatment
the Negative Predictive Value of Conversion at 2 Weeks for Relapse.
Time frame: at 2 weeks of treatment
Proportion of Acquired Rifampicin Resistance Among Failures and Relapses
Time frame: 12 months after end of TB treatment
Area Under the Curve of Auramine Resp. FDA at 2 Weeks to Predict Adverse Treatment Outcome at 1 Year After Treatment Completion
Time frame: Auramine/FDA at 2 weeks and adverse treatment outcome 1 year after treatment completion
Weight Gain
Time frame: until end of treatment (month eight)
Fever Resolution
Time frame: after 2 weeks of treatment
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Feb 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Aung Kya Jai Maug, MD principal investigator
Damien Foundation Bangladesh
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 double rimfampicin and Standard TB treatment in people with Tuberculosis, Pulmonary, run by Damien Foundation 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 7 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: finished, as of the sponsor's last update on 13 Feb 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?
Yes. Results are posted in the registry (first posted 13 Feb 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Tuberculose Treatment Outcome (time frame: 12 months after end of treatment). The study lists 2 primary outcomes in all. 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 13 Feb 2020.