Overview

This trial is active, not recruiting.

Condition tuberculosis, pulmonary
Treatments double rimfampicin, standard tb treatment
Phase phase 3
Sponsor Damien Foundation
Collaborator National TB control Programme Bangladesh
Start date November 2014
End date May 2017
Trial size 946 participants
Trial identifier NCT02153528, OneRIF

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Active Comparator)
Standard regimen for TB treatment according to guidelines of the International Union against Tuberculosis and Lung Disease
standard tb treatment Control arm
Standard regimen for TB treatment according to guidelines of the International Union against Tuberculosis and Lung Disease
(Experimental)
2HREZ/4HR Cat. 1, modified by using double dose rifampicin throughout
double rimfampicin Intervention arm
Compared to standard regimen dosing of rifampicin is doubled, while standard dose isoniazid, pyrazinamide and ethambutol are maintained

Primary Outcomes

Measure
Tuberculose treatment outcome
time frame: 12 months after end of treatment
Serious Adverse Events and Liver toxicity
time frame: until month eight

Secondary Outcomes

Measure
low-level rifampicin resistant TB adverse treatment outcomes
time frame: 12 months after end of TB treatment
effectiveness of standard auramine
time frame: at two weeks of treatment
assess the negative predictive value of conversion for relapse
time frame: at 2 weeks of treatment
estimate the proportion of acquired rifampicin resistance among failures and relapses
time frame: 12 months after end of TB treatment

Eligibility Criteria

Male or female participants at least 15 years old.

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

Additional Information

Official title Optimization of the TB Treatment Regimen Cascade
Principal investigator Aung Kya Jai Maug, MD
Trial information was received from ClinicalTrials.gov and was last updated in May 2016.
Information provided to ClinicalTrials.gov by Damien Foundation.