Limited role of culture conversion for decision-making in individual patient care and for advancing novel regimens to confirmatory clinical trials
Date
2016-02-04
Journal Title
Journal ISSN
Volume Title
Publisher
BioMed Central
Abstract
Background: Despite recent increased clinical trials activity, no regimen has proved able to replace the standard
6-month regimen for drug-sensitive tuberculosis. Understanding the relationship between microbiological markers
measured during treatment and long-term clinical outcomes is critical to evaluate their usefulness for decisionmaking
for both individual patient care and for advancing novel regimens into time-consuming and expensive
pivotal phase III trials.
Methods: Using data from the randomized controlled phase III trial REMoxTB, we evaluated sputum-based markers of
speed of clearance of bacilli: time to smear negative status; time to culture negative status on LJ or in MGIT; daily rate
of change of log10(TTP) to day 56; and smear or culture results at weeks 6, 8 or 12; as individual- and trial-level
surrogate endpoints for long-term clinical outcome.
Results: Time to culture negative status on LJ or in MGIT, time to smear negative status and daily rate of change in
log10(TTP) were each independent predictors of clinical outcome, adjusted for treatment (p <0.001). However,
discrimination between low and high risk patients, as measured by the c-statistic, was modest and not much higher
than the reference model adjusted for BMI, history of smoking, HIV status, cavitation, gender and MGIT TTP.
Conclusions: Culture conversion during treatment for tuberculosis, however measured, has only a limited role in
decision-making for advancing regimens into phase III trials or in predicting the outcome of treatment for individual
patients. REMoxTB ClinicalTrials.gov number: NCT00864383.
Description
CITATION: Phillips, P. P. J., et al. 2016. Limited role of culture conversion for decision-making in individual patient care and for advancing novel regimens to confirmatory clinical trials. BMC Medicine, 14:19, doi:10.1186/s12916-016-0565-y.
The original publication is available at https://bmcmedicine.biomedcentral.com
The original publication is available at https://bmcmedicine.biomedcentral.com
Keywords
Tuberculosis -- Treatment, Tuberculosis -- Clinical trials, Tuberculosis -- Microbiology, Tuberculosis -- Patients -- Care
Citation
Phillips, P. P. J., et al. 2016. Limited role of culture conversion for decision-making in individual patient care and for advancing novel regimens to confirmatory clinical trials. BMC Medicine, 14:19, doi:10.1186/s12916-016-0565-y