Phase 3
N=701
Optimization of the TB Treatment Regimen Cascade
Tuberculosis, Pulmonary
Bottom Line
View on ClinicalTrials.gov: NCT02153528 ↗Enrolled (actual)
701
Serious AEs
5.3%
Results posted
Feb 2020
Primary outcome: Primary: Tuberculose Treatment Outcome — 8; 8; 11; 5 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- double rimfampicin (Drug); Standard TB treatment (Drug)
- Age
- Pediatric, Adult, Older Adult · 15+ yrs
- Sex
- All
- Sponsor
- Damien Foundation
- Primary completion
- Aug 2017
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Tuberculose Treatment Outcome |
8; 8; 11; 5; 8; 12 | — |
| PRIMARY Number of Participants Who Develop Liver Toxicity |
7; 3 | — |
| SECONDARY High-level Rifampicin Resistant TB Adverse Treatment Outcomes |
52; 40; 281; 290; 0; 0 | — |
| SECONDARY Number of Initial Resistant TB Cases Who Switched to MDR-TB Treatment or Were Cured |
5; 2 | — |
| SECONDARY the Negative Predictive Value of Conversion at 2 Weeks for Relapse. |
0; 0 | — |
| SECONDARY Proportion of Acquired Rifampicin Resistance Among Failures and Relapses |
0; 0 | — |
| SECONDARY Area Under the Curve of Auramine Resp. FDA at 2 Weeks to Predict Adverse Treatment Outcome at 1 Year After Treatment Completion |
0.52; 0.54 | — |
| SECONDARY Weight Gain |
2.93; 2.79 | — |
| SECONDARY Fever Resolution |
81; 71 | — |
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. 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.
Eligibility Criteria
Inclusion Criteria
- Diagnosed with smear-positive pulmonary TB
- 15 years or older
- Able and willing to provide written informed consent
Exclusion Criteria
- 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
Data sourced from ClinicalTrials.gov (NCT02153528). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.