NGS-Guided(G) Regimens(R) of Anti-tuberculosis(A) Drugs for the Control(C) and Eradication(E) of MDR-TB
Status:
Not yet recruiting
Trial end date:
2024-08-04
Target enrollment:
Participant gender:
Summary
Tuberculosis (TB) has been one of the top 10 causes of death worldwide from a single
infectious agent, ranking above HIV/AIDS. Management and eradication of this disease is being
hindered by the emergence of multidrug-resistant TB (MDR-TB) and extensively drug resistant
TB (XDR-TB). Globally, there were estimated 10.4 million cases of TB and 490,000 cases of
MDR-TB in 2016. China accounts for around 8.6% (0.895/10.4 million) of the global TB burden,
ranking third in the top 3 countries (India, Indonesia, China) with the highest number of TB
cases and ranking first with the largest number of MDR/ Rifampin-Resistant (RR)-TB cases. The
treatment success rate for MDR-TB using the 18-24-month conventional World Health
Organization (WHO) regimen was estimated to be about 54% worldwide and 41% for China in 2016,
which remains unacceptably low.
The poor MDR-TB treatment success rates suggest that current drug regimens are suboptimal. In
addition, they are costly with a high pill burden, as many drugs, with significant potential
for adverse events, are given for a long duration. These factors also inhibit good treatment
compliance with further negative impact on treatment outcomes. According to previous studies,
treatment outcomes of MDR-TB could be affected by drug resistance of pivotal drugs in MDR-TB
regimen, such as fluoroquinolones, second-line injectable agents and pyrazinamide. The
available drug-resistance information could help physicians decide the proper regimens for
MDR-TB patients, which may prevent the useless prescription and evitable adverse.
Therefore, the individualized regimen based on the resistance profile of the bacteria and
patients' drug tolerance should be aimed for high-quality treatment for MDR-TB in the future.
A precision individualized treatment approach based on the rapid molecular drug
susceptibility tests of second line drugs may assist clinicians in making more suitable
regimen and improve the treatment outcome of MDR-TB. Also, precision regimen offers the
opportunity to improve treatment of drug-resistant tuberculosis through reduced toxicity
while reducing the risk of resistance amplification and further transmission at a population
level.
The purpose of this research is to assess the feasibility and effects of individualized
regimen that is guided by rapid molecular drug susceptibility tests of key second-line drugs
through next generation sequencing. Meanwhile, the study will evaluate a short course
regimens of drugs among "simple MDR-TB" patients who are proven to be sensitive to
fluoroquinolones ,injectable second-line drugs and pyrazinamide.