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

Multi-drug Resistant Tuberculosis Clinical Trial

Official title:

The Effect of New MDR-TB Regimen With 18 Month Duration Containing 6 Anti-tuberculosis Drugs

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03830671
• Other study ID #: 2018ZX10722301-001
• Status: Completed
• Phase: Phase 4
• Start date: March 8, 2019
• Est. completion date: June 8, 2022

Study information

• Verified date: October 2022
• Source: Beijing Chest Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 515
• Est. completion date: June 8, 2022
• Est. primary completion date: June 8, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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%

Related Conditions & MeSH terms

• Multi-drug Resistant Tuberculosis
• Tuberculosis
• Tuberculosis, Multidrug-Resistant

Intervention

Drug:
• 18-month regimen containing 6 anti-TB drugs
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

Locations

Country	Name	City	State
China	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	The Fourth People's Hospital of Inner Mongolia Autonomous region	Hohhot
China	Shandong Provincial Chest Hospital	Jinan
China	Shanghai Pulmonary Hospital	Shanghai
China	Shenyang Chest Hospital	Shenyang
China	Tianjin Haihe Hospital	Tianjin
China	Chest of Hospital of Xinjiang Uygur Autonomous Region of the PRC	Ürümqi
China	The Tuberculosis Prevention and Treatment Hospital of Shanxi Province	Xi'an
China	Xi'an Chest Hospital	Xi'an
China	The Fourth People's Hospital of Ningxia Autonomous Region	Yinchuan
China	The Infectious Disease Hospital of Wangkai Zaozhuang	Zaozhuang

Sponsors (1)

Lead Sponsor	Collaborator
Beijing Chest Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	the treatment success rate		at the end of treatment completion of all enrolled patients,an average of 18 months after the last patient enrolled
Primary	death rate		at the end of treatment completion of all enrolled patients, an average of 18 months after the last patient enrolled
Secondary	sputum conversion rate at the end of month 2, month 3,intensive phase and treatment completion.		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.
Secondary	Frequency of adverse drug reaction occurring during treatment.		at the end of treatment completion of all enrolled patients, an average of 18 months after the last enrolled patient.
Secondary	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.	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.