Clinical trial NCT02153528: Optimization of the TB Treatment Regimen Cascade
Official title: Optimization of the TB Treatment Regimen Cascade
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Tuberculosis, Pulmonary
Keywords: Bangladesh
Rimfapicin
Lead sponsor: Damien Foundation
Sponsor class: OTHER
Collaborators: name: National TB control Programme Bangladesh
name: Institute of Tropical Medicine, Belgium
First posted: 2014-06-03
Enrollment: 701
Sex: ALL
Minimum age (years): 15
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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

Primary outcomes:
measure: Tuberculose Treatment Outcome
timeFrame: 12 months after end of treatment
measure: Number of Participants Who Develop Liver Toxicity
timeFrame: until month eight
Secondary outcomes:
measure: High-level Rifampicin Resistant TB Adverse Treatment Outcomes
timeFrame: 12 months after end of TB treatment
measure: Number of Initial Resistant TB Cases Who Switched to MDR-TB Treatment or Were Cured
timeFrame: at two weeks of treatment
measure: the Negative Predictive Value of Conversion at 2 Weeks for Relapse.
timeFrame: at 2 weeks of treatment
measure: Proportion of Acquired Rifampicin Resistance Among Failures and Relapses
timeFrame: 12 months after end of TB treatment
measure: Area Under the Curve of Auramine Resp. FDA at 2 Weeks to Predict Adverse Treatment Outcome at 1 Year After Treatment Completion
timeFrame: Auramine/FDA at 2 weeks and adverse treatment outcome 1 year after treatment completion
measure: Weight Gain
timeFrame: until end of treatment (month eight)
measure: Fever Resolution
timeFrame: after 2 weeks of treatment
Other outcomes:
Locations:
city: Dhaka
country: Bangladesh
facility: Damien Foundation Bangladesh TB project in Greater Mymensingh district (8 selected clinics)
state: Greater Mymensingh District
Study officials:
affiliation: Damien Foundation Bangladesh
name: Aung Kya Jai Maug, MD
role: PRINCIPAL_INVESTIGATOR
References: