Clinical trial NCT04545788: Randomized Controlled Multi-center Short Course Treatment for Rifampicin Resistant Tuberculosis
Official title: A Randomized, Controlled, Multi-center Clinical Trial of Short Course Treatment for Newly Diagnosed Rifampicin Resistant Tuberculosis
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Tuberculosis
Keywords: Tuberculosis, rifampin resistant, oral, shorter.
Lead sponsor: Beijing Chest Hospital
Sponsor class: OTHER
First posted: 2020-09-11
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study is a randomized, controlled, multi-center clinical study. The main purpose of this study was to study the efficacy and safety data of total oral short-term therapy as an alternative to injection in the treatment of newly diagnosed RR-TB patients.

Detailed description: A group: 4-6 INH EMB PZA Pto AM Cfz Mfx / 5 EMB PZA Cfz Mfx B group: 4-6 INH EMB PZA Pto LZD Cfz Mfx / 5 EMB PZA Cfz Mfx C group: 4-6 BDQ LZD MFX CS CFZ / 5MFX CS CFZ (INH: Isoniazid, EMB: Ethambutol, PZA: Pyrazinamide, Pto: Prothionamide, AM: Amikacin, Cfz: Clofazimine, Mfx: Moxifloxacin, LZD: Linezolid, BDQ: Bedaquiline, CS: Cycloserine) A group is the control group which includes injectable drugs (AM). B group and C group are the experimental groups which are total oral short-term therapy.

Eligibility criteria: Inclusion Criteria:

* signed informed consent and accepted follow-up;
* the age is between 18 and 65 years old, both male and female, including inpatients and outpatients;
* no use of anti tuberculosis drugs, or use of anti tuberculosis drugs less than 1 month;
* the results of molecular biology test confirmed rifampicin resistance or MDR-TB patients;
* chest CT examination confirmed pulmonary tuberculosis, pulmonary lesions, or cavity;
* premenopausal women had negative pregnancy urine test and agreed to use high-efficiency contraceptive measures during the study period.

Exclusion Criteria:

* drug sensitivity test or molecular drug sensitivity results show that the drug resistance (except isoniazid) or any component of the drug has a history of allergy, or is taking any drug that is contraindicated to the drug in the short-term treatment program;
* severe renal insufficiency (creatinine clearance rate (CrCl) less than 30 ml / min).
* liver function impairment (ALT and / or AST level 3 times higher than the upper limit of laboratory reference value, if it is temporary increase, it can be included after treatment recovery);
* those who are unable to participate in or comply with the treatment and follow-up;
* Q-T interval \> 450 millisecond;
* have a history of cardiovascular diseases or are suffering from such diseases as heart failure, hypertension (poor blood pressure control), arrhythmia or post myocardial infarction state;
* pregnant or lactating women;
* those who are unable to take oral drugs;
* those who are currently participating in other clinical trials;
* patients with HIV positive or active viral hepatitis.

Primary outcomes:
measure: Culture of Mycobacterium tuberculosis in sputum.
timeFrame: Through study completion, an average of 1 year.
Secondary outcomes:
measure: Adverse effect.
timeFrame: Through study completion, an average of 1 year.
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Chest Hospital affiliated to Capital Medical University
state: Beijing
Study officials:
affiliation: Beijing Chest Hospital affiliated to Capital Medical University
name: NAIHUI CHU, Doctor
role: PRINCIPAL_INVESTIGATOR
References:
citation: Du Y, Qiu C, Chen X, Wang J, Jing W, Pan H, Chen W, Liu Y, Li C, Xi X, Yin H, Zeng J, Zhang X, Xu T, Wang Q, Guo R, Wang J, Pang Y, Chu N. Treatment Outcome of a Shorter Regimen Containing Clofazimine for Multidrug-resistant Tuberculosis: A Randomized Control Trial in China. Clin Infect Dis. 2020 Aug 14;71(4):1047-1054. doi: 10.1093/cid/ciz915.
citation: Wang Q, Pang Y, Jing W, Liu Y, Wang N, Yin H, Zhang Q, Ye Z, Zhu M, Li F, Liu P, Wu T, Chen W, Wu W, Qin Z, Qiu C, Deng Q, Xu T, Wang J, Guo R, Du Y, Wang J, Huang H, Chen X, Chu N. Clofazimine for Treatment of Extensively Drug-Resistant Pulmonary Tuberculosis in China. Antimicrob Agents Chemother. 2018 Mar 27;62(4):e02149-17. doi: 10.1128/AAC.02149-17. Print 2018 Apr.
citation: Wang J, Pang Y, Jing W, Chen W, Guo R, Han X, Wu L, Yang G, Yang K, Chen C, Jiang L, Cai C, Dou Z, Diao L, Pan H, Wang J, Du F, Xu T, Wang L, Li R, Chu N. Efficacy and safety of cycloserine-containing regimens in the treatment of multidrug-resistant tuberculosis: a nationwide retrospective cohort study in China. Infect Drug Resist. 2019 Apr 3;12:763-770. doi: 10.2147/IDR.S194484. eCollection 2019.
citation: Pang Y, Jing W, Lu J, Zong Z, Huo F, Dong L, Dai G, Li Y, Huang H, Chu N. No in vitro synergistic effect of bedaquiline combined with fluoroquinolones, linezolid, and clofazimine against extensively drug-resistant tuberculosis. Diagn Microbiol Infect Dis. 2019 Aug;94(4):361-364. doi: 10.1016/j.diagmicrobio.2019.02.012. Epub 2019 Feb 19.