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

December 4, 2019 updated by: Li Ding, Fifth Affiliated Hospital, Sun Yat-Sen University

A Prospective, Randomized Controlled Study for the Efficacy and Safety of the Substitution of Pyrazinamide and Ethambutol With Moxifloxacin During the Intensive Phase of Treatment of Pulmonary Tuberculosis

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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

The standard initial regimen for PTB consists of an initial 2-month intensive phase followed by a 4-month continuation phase. In the initial 2-month intensive phase, patients have to take four drugs-isoniazid, rifampin, pyrazinamide and ethambutol (HRZE) which might cause many adverse reactions. During the intensive phase, patients are prone to poor compliance due to adverse reactions, resulting in poor outcomes and drug-resistance. Therefore, it is necessary to optimize the regimen of intensive phase to improve patients' medication compliance, so as to avoid patients' treatment failure or drug resistance.

Moxifloxacin(M) has high antibacterial activity against both intracellular and extracellular Mycobacterium tuberculosis (Mtb) with few adverse reactions and is the most promising alternative to first-line anti-TB drugs. Isoniazid and rifampin have a strong bactericidal effect on both intracellular and extracellular Mtb. In the initial regimen for PTB, isoniazid and rifampin should be used throughout the whole process. They are the key drugs to ensure the curative effect and prevent recurrence, can not be easily replaced. But pyrazinamide and ethambutol just be used in the intensive phase. Pyrazinamide has the strongest killing effect on the intracellular Mtb and mainly exerts its antibacterial effect in the first two months of treatment. Ethambutol is a bacteriostatic drug, mainly effective for rapidly growing Mtb outside cells. They can lead to severe gastrointestinal reactions, liver damage, papilledema and other adverse reactions. So moxifloxacin might be an optional substitute for pyrazinamide and ethambutol.

This study will involve comparisons that are designed to assess the short-term efficacy, safety, relapse rate one year after drug withdrawal and patients' compliance when substituting moxifloxacin for pyrazinamide and ethambutol in the existing standard regimen. Patients selected for the study will be allocated to the trial group or the control group randomly. The control group will be given six months of a standard regimen(2HRZE/4HR). The trial group will be given a total of six months of treatment, with Substitution of pyrazinamide and ethambutol with moxifloxacin during the intensive phase(2HRM/4HR).

Study Type

Interventional

Enrollment (Anticipated)

286

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
    • Guangdong
      • Zhuhai, Guangdong, China, 519000
        • The Fifth Affiliated Hospital Sun Yat-Sen University
        • Contact:
          • Li Ding, Doctor
          • Phone Number: +8613926921192

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.
  • Any other circumstances in which the anti-tuberculosis scheme of the experimental group or the control group cannot be selected for treatment.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Regimen 1: 2HRM/4HR
Two month of chemotherapy with Moxifloxacin, Isoniazid and Rifampicin, followed by four month of Isoniazid and Rifampicin only.
Drug: Moxifloxacin, Isoniazid, Rifampicin

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.

Other Names:
  • Avelox, Myambutol, Nydrazid, Rifampin, Rifadin
Active Comparator: Regimen 2: 2HRZE/4HR (control regimen)
Two month of chemotherapy with Isoniazid, Rifampicin, Pyrazinamide and Ethambutol, followed by four month of Isoniazid and Rifampicin only.
Drug: Rifampicin,Isoniazid,Pyrazinamide,Ethambutol

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.

Other Names:
  • Myambutol,Nydrazid,Rifampin,Rifadin

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The rate of adverse outcomes
Time Frame: 18 months (within one year of completion of therapy）

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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
The rate of Treatment success
Time Frame: the 2nd, 3rd, 5th and 6th months

Treatment success: A sum of cured and completed treatment.

Cure: A patient whose sputum smear or culture was positive at the beginning of the treatment but who was smear- or culture-negative in the last month of treatment and on at least one previous occasion.

Treatment completed: A patient who completed treatment but who does not have a negative sputum smear or culture result in the last month of treatment and on at least one previous occasion.
the 2nd, 3rd, 5th and 6th months
The rate of sputum Mtb negative conversion
Time Frame: the 2nd, 3rd, 5th and 6th months
Sputum Mtb negative conversion: two negative-culture results at different visits without an intervening positive result, or no sputum could be tested after once negative-culture.
the 2nd, 3rd, 5th and 6th months
The time of sputum Mtb negative conversion
Time Frame: the 2nd, 3rd, 5th and 6th months
The first time of sputum Mtb negative conversion
the 2nd, 3rd, 5th and 6th months
Number of Patients With Adverse Events
Time Frame: 18 months (within one year of completion of therapy)
The number of participants includes all patients who had adverse event.
18 months (within one year of completion of therapy)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Fifth Affiliated Hospital, Sun Yat-Sen University

Investigators

  • Study Director: Li Ding, M.D, The Fifth Affiliated Hospital Sun Yat-Sen University
  • Principal Investigator: 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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

March 1, 2020

Primary Completion (Anticipated)

February 1, 2023

Study Completion (Anticipated)

February 1, 2024

Study Registration Dates

First Submitted

December 3, 2019

First Submitted That Met QC Criteria

December 4, 2019

First Posted (Actual)

December 5, 2019

Study Record Updates

Last Update Posted (Actual)

December 5, 2019

Last Update Submitted That Met QC Criteria

December 4, 2019

Last Verified

December 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ZDWY.GRK.004

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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