NGS-Guided(G) Regimens(R) of Anti-tuberculosis(A) Drugs for the Control(C) and Eradication(E) of MDR-TB (GRACE-TB)
Multidrug Resistant Tuberculosis
About this trial
This is an interventional treatment trial for Multidrug Resistant Tuberculosis focused on measuring Multidrug Resistant Tuberculosis, next generation sequencing, drug susceptibility test, precision treatment
Eligibility 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.
Sites / Locations
- The Third People's Hospital of Shenzhen City
- the First Affiliated Hospital of Harbin Medical University
- The Sixth People's Hospital of Zhengzhou
- The Fifth People's Hospital of Suzhou
- The Affiliated Hospital of Southwest Medical University
- Chest Hospitalof Xinjiang Uygur Autonomous Region of PRC
- Zhuji City People's Hospital
- Hangzhou Red Cross Hospital
- Zhejiang Provincial Center for Disease Control and Prevention
- The Second Hospital of Yinzhou of Ningbo
- Enze Medical Center of Taizhou CIty
- The Central Hospital of Wenzhou City
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Experimental
Experimental
Experimental
Active Comparator
NGS-guided regimen: Regimen A
NGS-guided regimen: Regimen B
NGS-guided regimen: Regimen C
WHO-approved MDR-TB regimen
Regimen A: 9-month regimen for simple MDR-TB patients 4 months of pyrazinamide, amikacin ,moxifloxacin, prothionamide, and cycloserine , followed by 5months of pyrazinamide,moxifloxacin, prothionamide, and cycloserine
Regimen B: 12-month simple MDR-TB regimen for simple MDR-TB patients 6 months of pyrazinamide, amikacin ,moxifloxacin, prothionamide, and cycloserine , followed by 6 months of pyrazinamide,moxifloxacin, prothionamide, and cycloserine
Regimen C : for complicated MDR-TB patients In regimen C, the resistant drug(s) will be replaced by the other WHO recommended drugs for MDR-TB such as linezolid, clofazimine or ethambutol based on the drug susceptibility test results. The duration of treatment in the "complicated MDR-TB group" is consistent with control group, with 6 months of intensive phase and 18 months of consolidation phase.
6 months of pyrazinamide, amikacin,moxifloxacin, prothionamide , and cycloserine , followed by 18 months of pyrazinamide, moxifloxacin, prothionamide , and cycloserine