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: 0
• Participant gender: All

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.

• Phase: N/A
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Huashan Hospital
• Treatments: Amikacin; Antitubercular Agents; Clofazimine; Cycloserine; Ethambutol; Linezolid; Moxifloxacin; Norgestimate, ethinyl estradiol drug combination; Prothionamide; Pyrazinamide

Criteria

Inclusion Criteria:

• Patients who are diagnosed with active MDR-TB. MDR-TB is defined as resistance to the following two drugs: Isoniazid and Rifampicin.

• Patients who are smear positive and sputum culture positive for mycobacterium tuberculosis

• HIV negative.

• The patients should be voluntarily entering the study and willing to sign up the consent form after full knowledge of the risks, schedule, drug features of this study.

Exclusion Criteria:

• Known allergy or intolerance to the drugs in this study

• Liver damage (Hepatic encephalopathy; ascites; prothrombin time prolonged 2 seconds compared with normal controls; blood bilirubin 3 times greater than the upper limit of the normal range)

• Platelets <150x10^9 / L, WBC < 3x10^9 / L.

• Abnormal ECG (Male patients with prolonged QT interval exceeding 430ms,

• Female patients with prolonged QT interval exceeding 450ms)

• Serum creatinine 1.5 times higher than upper limit

• Fasting blood-glucose higher than 8.0 mmol/L

• Patients who are on medication that effect the results of the drugs in this study Karnofsky score<50% (see appendix)

• Women who are pregnant or breastfeeding

• HIV positive

• Participating in other clinical trials in the past three months

• Patients with mental illness and severe neurosis

• Patients who have poor compliances

• Any special circumstances in which the research physicians believe that is not suitable for this study.