The Effect of 18-month Regimen Containing 6 Anti-tuberculosis Drugs for Patients With MDR-TB

Beijing Chest Hospital515 enrolled

Overview

WHO has recommended that multidrug-resistant tuberculosis (MDR-TB, defined as resistance to at least isoniazid (H) and rifampicin (R) be addressed as a public health crisis and enhance capacity to deliver effective treatment and care. According to the 2018 WHO TB Report, the overall treatment success rate of MDR-TB is 55% while much lower in China at just only 41% with the 24-month regimen. In order to further verify the safety and efficiency of optimizing shorter 18-month regimen containing 6 anti-TB drugs with MDR-TB patients,500 more patients will be enrolled and observed.

1. Design: the study is a multi-center,open, single arm trial. 2. Population:patients with sputum culture positive and confirmed as MDR-TB via drug resistance of isoniazid(H),rifampicin(R),ethambutol(E)and pyrazinamide or patients with GeneXpert confirmed RR-TB. 3. Investigational regimen:3Am-Mfx-PZA-X-Y-Z/3Am3-Mfx-PZA-X-Y-Z/12 Mfx-PZA-X-Y-Z.X、Y、Z are the drugs susceptible or possibly susceptible to mycobacterial bacilli(The candidated drugs to be selected are:Cs-Cycloserine,Pto-Protionamide,Clr-Clarithromycin,PAS-sodium para-aminosalicylate,E-ethambutol,Bdq-Bedaquiline,Cfz-Clofazimine,Lzd-linezolid).The abbreviation of the name of the 3 drugs in the regimen is explained as follows: PZA-pyrazinamide，Am-Amikacin，Mfx-moxifloxacin）and the total duration of the regimen is 18 months. 4. Primary and secondary outcome measures: The primary outcome measures include 1.the treatment success rate.2. Death rate. The secondary outcome measures include 1.sputum conversion rate at the end of month 2, month 3,intensive phase of 6 months and treatment completion of all enrolled patients.2.Frequency of adverse drug reaction occurring during treatment.3.Radiological manifestation change of TB lesion or cavity during treatment. 5. Sample size: 500 eligible patients will be enrolled.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Interventions

18-month regimen containing 6 anti-TB drugsDRUG

Investigational regimen:3Am-Mfx-PZA-X-Y-Z/3Am3-Mfx-PZA-X-Y-Z/12 Mfx-PZA-X-Y-Z.X、Y、Z are the drugs susceptible or possibly susceptible to mycobacterial bacilli(The candidated drugs to be selected are:Cs-Cycloserine,Pto-Protionamide,Clr-Clarithromycin,PAS-sodium para-aminosalicylate,E-ethambutol,Bdq-Bedaquiline,Cfz-Clofazimine,Lzd-linezolid).The abbreviation of the name of each drug in the regimen is explained as follows: PZA-pyrazinamide，Am-Amikacin，Mfx-moxifloxacin）and the total duration of the regimen is 18 months

Eligibility

Sex: ALLMin age: 18 YearsMax age: 70 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Is willing and able to give informed consent to participate in the trial treatment and follow-up. * Is aged between 18 years and 70 years. * Has a positive sputum culture result or a positive GeneXpert result. * Has evidence of RR-TB or MDR-TB either by GeneXpert or culture-based drug susceptibility testing (DST). * Non pre-XDR-TB or XDR-TB. * Is willing to use effective contraception of women at childbearing age. * Has had a chest X-ray that is compatible with a diagnosis of pulmonary TB. Exclusion Criteria: * pre-XDR-TB or XDR-TB. * Has a known allergy to any drug of the regimen. * Is currently taking or took part in another trial less than three months before the study initiation . * Is HIV positive. * Has abnormal ECG with QT prolongation over 430ms of men while 450 of women. * Is critically ill, and in the judgment of the investigator, unlikely to take part in the study.Or has any condition (social or medical) which in the opinion of the investigator would make study participation unsafe. * Is known to be pregnant or breast-feeding. * Has severe cardiovascular diseases, such as heart failure, hypertension (poor blood pressure control), arrhythmia or post-infarction status. * Has severe concomitant severe disease such as respiratory failure or cardiac insufficiency or liver and kidney injury with aspartate aminotransferase (AST) or alanine aminotransferase (ALT) more than 2.5 times the upper limit of normal or with serum creatinine(Cr)more than 1.3 times the upper limit of normal. * Has Karnofsky score less than 50%

Locations (20)

Beijing Chest Hospital

Beijing, China

The 8th Medical Center of Chinese Pla General Hospital

Beijing, China

Changchun Infectious Disease Hospital

Changchun, China

Hunan Institute For Tuberculosis Control

Changsha, China

Public Health Clinical Center of Chengdu

Chengdu, China

Shenzhen Third Peple's Hospital

Guangzhou, China

Guangzhou Chest Hospital

Guanzhou, China

The Affiliated Hospital of Guizhou Medical University

Guiyang, China

Infectious Disease Prevention Hospital in Heilongjiang Province

Harbin, China

Anhui Chest Hospital

Hefei, China

...and 10 more locations

Outcomes

Primary Outcomes

the treatment success rate

Time frame: at the end of treatment completion of all enrolled patients,an average of 18 months after the last patient enrolled

death rate

Time frame: at the end of treatment completion of all enrolled patients, an average of 18 months after the last patient enrolled

Secondary Outcomes

sputum conversion rate at the end of month 2, month 3,intensive phase and treatment completion.

Time frame: at the end of month 2, month 3,intensive phase of 6 months since treatment initiation and treatment completion of all enrolled patients, an average of 18 months after the last enrolled patient.

Frequency of adverse drug reaction occurring during treatment.

Time frame: at the end of treatment completion of all enrolled patients, an average of 18 months after the last enrolled patient.

Radiological manifestation change of TB lesion or cavity at the end of month 2, month 3,intensive phase and treatment completion.

proportion of lung field the lesion accumulated taken up at different time points with the comparison to that at baseline. The number and size of cavities at different time points with comparison to that at baseline.