Randomized Controlled Multi-center Short Course Treatment for Rifampicin Resistant Tuberculosis

A Randomized, Controlled, Multi-center Clinical Trial of Short Course Treatment for Newly Diagnosed Rifampicin Resistant Tuberculosis

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.

Study Overview

• Status: Recruiting
• Conditions: Tuberculosis
• Intervention / Treatment: Drug: Total oral short-term therapy that includes linezolid, bedaquiline and/or cycloserine.

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.

• Study Type: Interventional
• Enrollment (Anticipated): 200
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: WENJUAN NIE, Director; Phone Number: +86 13552156672; Email: wenjuan.nie@outlook.com
• Study Contact Backup: Name: JING LIU, Doctor; Phone Number: +86 13810654836; Email: liujingworkbj@126.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 101149
      • Recruiting
      • Beijing Chest Hospital affiliated to Capital Medical University
      • Contact: NAIHUI CHU, Director; Phone Number: +86 10 89509301; Email: dongchu1994@sina.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 63 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: A; 4-6 INH EMB PZA Pto AM Cfz Mfx / 5 EMB PZA Cfz Mfx (INH: Isoniazid, EMB: Ethambutol, PZA: Pyrazinamide, Pto: Prothionamide, AM: Amikacin, Cfz: Clofazimine, Mfx: Moxifloxacin) A group is the control group which includes injectable drugs (AM).	Drug: Total oral short-term therapy that includes linezolid, bedaquiline and/or cycloserine.; AM is the traditional anti-TB drugs. Linezolid, bedaquiline and/or cycloserine, that might have potential efficacy of replacing injectable anti-TB drugs, are included into the total oral short-term therapy, and replace AM.
Experimental: B; 4-6 INH EMB PZA Pto LZD Cfz Mfx / 5 EMB PZA Cfz Mfx (INH: Isoniazid, EMB: Ethambutol, PZA: Pyrazinamide, Pto: Prothionamide, LZD: Linezolid, Cfz: Clofazimine, Mfx: Moxifloxacin) B group is the experimental groups which is total oral short-term therapy.	Drug: Total oral short-term therapy that includes linezolid, bedaquiline and/or cycloserine.; AM is the traditional anti-TB drugs. Linezolid, bedaquiline and/or cycloserine, that might have potential efficacy of replacing injectable anti-TB drugs, are included into the total oral short-term therapy, and replace AM.
Experimental: C; 4-6 BDQ LZD MFX CS CFZ / 5MFX CS CFZ (BDQ: Bedaquiline, LZD: Linezolid, Mfx: Moxifloxacin, CS: Cycloserine, Cfz: Clofazimine) C group is another experimental groups which is also total oral short-term therapy, and includes new anti-TB drugs: BDQ.	Drug: Total oral short-term therapy that includes linezolid, bedaquiline and/or cycloserine.; AM is the traditional anti-TB drugs. Linezolid, bedaquiline and/or cycloserine, that might have potential efficacy of replacing injectable anti-TB drugs, are included into the total oral short-term therapy, and replace AM.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Culture of Mycobacterium tuberculosis in sputum.	Mycobacterium tuberculosis culture of sputum will be carried out every month to understand the negative conversion rate and time of sputum bacteria, and then to understand the cure rate of patients. The final aim is to understand the efficacy of the total oral short-term anti-tuberculosis regimen.	Through study completion, an average of 1 year.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse effect.	All the types and frequency of adverse reactions that related to anti-tuberculosis drug were collected.	Through study completion, an average of 1 year.

Collaborators and Investigators

• Sponsor: Beijing Chest Hospital
• Investigators: Principal Investigator: NAIHUI CHU, Doctor, Beijing Chest Hospital affiliated to Capital Medical University

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2020
• Primary Completion (Anticipated): December 31, 2022
• Study Completion (Anticipated): December 31, 2022

Study Registration Dates

• First Submitted: August 31, 2020
• First Submitted That Met QC Criteria: September 4, 2020
• First Posted (Actual): September 11, 2020

Study Record Updates

• Last Update Posted (Actual): September 16, 2020
• Last Update Submitted That Met QC Criteria: September 11, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Keywords: Tuberculosis, rifampin resistant, oral, shorter.
• Additional Relevant MeSH Terms: Infections; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Actinomycetales Infections; Mycobacterium Infections; Tuberculosis; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antimetabolites; Anti-Bacterial Agents; Protein Synthesis Inhibitors; Antitubercular Agents; Antibiotics, Antitubercular; Anti-Infective Agents, Urinary; Renal Agents; Linezolid; Cycloserine; Bedaquiline
• Other Study ID Numbers: GCP-TB

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No