Efficacy and Safety of Isoniazid, Rifampicin and Moxifloxacin for the Intensive Phase of Initial Therapy of PTB

NCT04187469 | Unknown

• 1 other identifier: ZDWY.GRK.004
• Study Type: interventional
• Target: 286
• Locations: 1 country
• Sites: 1

Brief Summary

This study aims to find an optimized initial regimen for pulmonary tuberculosis(PTB), evaluating the efficacy, safety and acceptability of isoniazid, rifampicin and moxifloxacin(HRM) for the intensive phase of initial therapy of PTB, compared with the standard initial regimen.

Conditions

Pulmonary Tuberculosis

Keywords

Pulmonary Tuberculosis; Anti-tuberculosis therapy; Intensive phase; Moxifloxacin; initial regimen

Outcome Measures

Primary Outcomes (1)

• The rate of adverse outcomes

  Adverse outcomes: A sum of treatment failure and relapse. Treatment failure: A patient whose sputum smear or culture is positive at 5 months or later during treatment. Relapse: patients with successful treatment show one of the following conditions at any time point during the observation period of drug withdrawal: 1) Sputum or Bronchoalveolar lavage fluid(BALF)culture positive, 2) Sputum or BALF acid fast stain and/or Xpert positive with active PTB evidence in CT scan.

  18 months (within one year of completion of therapy）

Secondary Outcomes (4)

• The rate of Treatment success

  the 2nd, 3rd, 5th and 6th months

• The rate of sputum Mtb negative conversion

  the 2nd, 3rd, 5th and 6th months

• The time of sputum Mtb negative conversion

  the 2nd, 3rd, 5th and 6th months

• Number of Patients With Adverse Events

  18 months (within one year of completion of therapy)

Study Arms (2)

Regimen 1: 2HRM/4HR

EXPERIMENTAL

Two month of chemotherapy with Moxifloxacin, Isoniazid and Rifampicin, followed by four month of Isoniazid and Rifampicin only.

Drug: Moxifloxacin, Isoniazid, Rifampicin

Regimen 2: 2HRZE/4HR (control regimen)

ACTIVE COMPARATOR

Two month of chemotherapy with Isoniazid, Rifampicin, Pyrazinamide and Ethambutol, followed by four month of Isoniazid and Rifampicin only.

Drug: Rifampicin,Isoniazid,Pyrazinamide,Ethambutol

Interventions

Moxifloxacin, Isoniazid, Rifampicin DRUG

Moxifloxacin 400 mg/day, Rifampicin ≤50 kg 450 mg/day \> 50 kg 600 mg/day, Isoniazid 300 mg/day. All treatment is taken daily, for a duration of up to 6 months depending on treatment arm.

Also known as: Avelox, Myambutol, Nydrazid, Rifampin, Rifadin

Regimen 1: 2HRM/4HR

Rifampicin,Isoniazid,Pyrazinamide,Ethambutol DRUG

Rifampicin ≤50 kg 450 mg/day, \>50 kg 600 mg/day, Isoniazid 300 mg/day, Pyrazinamide 1500mg/day, Ethambutol ≤50 kg or the elderly 750mg/day, \>50 kg 1000mg/day. All treatment is taken daily, for a duration of up to 26 weeks depending on treatment arm.

Also known as: Myambutol,Nydrazid,Rifampin,Rifadin

Regimen 2: 2HRZE/4HR (control regimen)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged 18 years or over, and an individual who completely bear the ability of civil actions.
• New cases of pulmonary tuberculosis. No previous anti-tuberculosis therapy or cumulatively taking anti-tuberculosis drugs for less than 1 month.
• Pulmonary tuberculosis patients with bacteriological diagnosis.

You may not qualify if:

• Suffering from tuberculous pleurisy.
• Patients with extrapulmonary tuberculosis.
• Renal insufficiency patients with creatinine clearance rate \<30 ml/min.
• Abnormal liver function (ALT and/or AST and/or TBIL greater than 2 times the upper limit of normal) or decompensated cirrhosis.
• HIV-Ab positive.
• Psychiatric patients, or have a previous history of mental illness, or recently have obvious anxiety or depression and other mental abnormalities.
• Patients receiving immunosuppressive therapy.
• Pregnant or breast feeding.
• Diabetes.
• X-pert MTB/RIF test of sputum or alveolar lavage fluid showed that Mycobacterium tuberculosis was rifampin resistant.
• Moxifloxacin was used within 14 days before entering the group.
• Anti-tuberculosis treatment has been started and drugs are being taken before entering the group.
• QT interval extension \> 480 ms.
• Combined with serious cardiovascular, liver, kidney, nervous system, blood system and other diseases or tumor diseases.
• Pulmonary lesions are widespread with respiratory insufficiency.

Sponsors & Collaborators

• Fifth Affiliated Hospital, Sun Yat-Sen University: lead

Study Sites (1)

The Fifth Affiliated Hospital Sun Yat-Sen University

Zhuhai, Guangdong, 519000, China

Location

Related Publications (8)

• Tiberi S, du Plessis N, Walzl G, Vjecha MJ, Rao M, Ntoumi F, Mfinanga S, Kapata N, Mwaba P, McHugh TD, Ippolito G, Migliori GB, Maeurer MJ, Zumla A. Tuberculosis: progress and advances in development of new drugs, treatment regimens, and host-directed therapies. Lancet Infect Dis. 2018 Jul;18(7):e183-e198. doi: 10.1016/S1473-3099(18)30110-5. Epub 2018 Mar 23.

  PMID: 29580819 BACKGROUND

• Lange C, Chesov D, Heyckendorf J, Leung CC, Udwadia Z, Dheda K. Drug-resistant tuberculosis: An update on disease burden, diagnosis and treatment. Respirology. 2018 Jul;23(7):656-673. doi: 10.1111/resp.13304. Epub 2018 Apr 11.

  PMID: 29641838 BACKGROUND

• Pasipanodya JG, Gumbo T. A meta-analysis of self-administered vs directly observed therapy effect on microbiologic failure, relapse, and acquired drug resistance in tuberculosis patients. Clin Infect Dis. 2013 Jul;57(1):21-31. doi: 10.1093/cid/cit167. Epub 2013 Mar 13.

  PMID: 23487389 BACKGROUND

• Egelund EF, Alsultan A, Peloquin CA. Optimizing the clinical pharmacology of tuberculosis medications. Clin Pharmacol Ther. 2015 Oct;98(4):387-93. doi: 10.1002/cpt.180. Epub 2015 Jul 22.

  PMID: 26138226 BACKGROUND

• Pienaar E, Sarathy J, Prideaux B, Dietzold J, Dartois V, Kirschner DE, Linderman JJ. Comparing efficacies of moxifloxacin, levofloxacin and gatifloxacin in tuberculosis granulomas using a multi-scale systems pharmacology approach. PLoS Comput Biol. 2017 Aug 17;13(8):e1005650. doi: 10.1371/journal.pcbi.1005650. eCollection 2017 Aug.

  PMID: 28817561 BACKGROUND

• Xu P, Chen H, Xu J, Wu M, Zhu X, Wang F, Chen S, Xu J. Moxifloxacin is an effective and safe candidate agent for tuberculosis treatment: a meta-analysis. Int J Infect Dis. 2017 Jul;60:35-41. doi: 10.1016/j.ijid.2017.05.003. Epub 2017 May 8.

  PMID: 28495364 BACKGROUND

• Gillespie SH, Crook AM, McHugh TD, Mendel CM, Meredith SK, Murray SR, Pappas F, Phillips PP, Nunn AJ; REMoxTB Consortium. Four-month moxifloxacin-based regimens for drug-sensitive tuberculosis. N Engl J Med. 2014 Oct 23;371(17):1577-87. doi: 10.1056/NEJMoa1407426. Epub 2014 Sep 7.

  PMID: 25196020 BACKGROUND

• Chakraborty S, Rhee KY. Tuberculosis Drug Development: History and Evolution of the Mechanism-Based Paradigm. Cold Spring Harb Perspect Med. 2015 Apr 15;5(8):a021147. doi: 10.1101/cshperspect.a021147.

  PMID: 25877396 BACKGROUND

Related Links

• Definitions and reporting framework for tuberculosis

MeSH Terms

Conditions

Tuberculosis, Pulmonary

Interventions

Moxifloxacin; Isoniazid; Rifampin; Ethambutol

Condition Hierarchy (Ancestors)

Tuberculosis; Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Hydrazines; Organic Chemicals; Isonicotinic Acids; Acids, Heterocyclic; Pyridines; Heterocyclic Compounds, 1-Ring; Rifamycins; Heterocyclic Compounds, 4 or More Rings; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds; Ethylenediamines; Diamines; Polyamines; Amines

Study Officials

• Li Ding, M.D

  The Fifth Affiliated Hospital, Sun Yat-sen University

  STUDY DIRECTOR

• Yuanli Chen, M.Med

  The Fifth Affiliated Hospital, Sun Yat-sen University

  PRINCIPAL INVESTIGATOR

• Xi Liu, M.D

  The Fifth Affiliated Hospital, Sun Yat-sen University

  PRINCIPAL INVESTIGATOR

• JinYu Xia, M.Med

  The Fifth Affiliated Hospital, Sun Yat-sen University

  PRINCIPAL INVESTIGATOR

• Zhongsi Hong, M.Med

  The Fifth Affiliated Hospital, Sun Yat-sen University

  PRINCIPAL INVESTIGATOR

• Jian Liu, M.D

  The Fifth Affiliated Hospital, Sun Yat-sen University

  PRINCIPAL INVESTIGATOR

• Minyi Lin, M.Med

  The Fifth Affiliated Hospital, Sun Yat-sen University

  PRINCIPAL INVESTIGATOR

• Lisi Deng, M.Med

  The Fifth Affiliated Hospital, Sun Yat-sen University

  PRINCIPAL INVESTIGATOR

• Lei Luo

  The Fifth Affiliated Hospital, Sun Yat-sen University

  PRINCIPAL INVESTIGATOR

• Yayi Huang

  The Fifth Affiliated Hospital, Sun Yat-sen University

  PRINCIPAL INVESTIGATOR

• Xiaoqing Luo

  The Fifth Affiliated Hospital, Sun Yat-sen University

  PRINCIPAL INVESTIGATOR

• Yin Li

  The Fifth Affiliated Hospital, Sun Yat-sen University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Li Ding, M.D

CONTACT

13926921192; dingli@mail.sysu.edu.cn

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate chief physician of infectious diseases

Study Record Dates

• First Submitted: December 3, 2019
• First Posted: December 5, 2019
• Study Start: March 1, 2020
• Primary Completion: February 1, 2023
• Study Completion: February 1, 2024
• Last Updated: December 5, 2019

Record last verified: 2019-12

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)