Clinical trial NCT04187469: Efficacy and Safety of Isoniazid, Rifampicin and Moxifloxacin for the Intensive Phase of Initial Therapy of PTB
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Pulmonary Tuberculosis
Keywords: Pulmonary Tuberculosis
Anti-tuberculosis therapy
Intensive phase
Moxifloxacin
initial regimen
Lead sponsor: Fifth Affiliated Hospital, Sun Yat-Sen University
Sponsor class: OTHER
First posted: 2019-12-05
Enrollment: 286
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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).

Eligibility criteria: 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.

Primary outcomes:
measure: The rate of adverse outcomes
timeFrame: 18 months (within one year of completion of therapy）
Secondary outcomes:
measure: The rate of Treatment success
timeFrame: the 2nd, 3rd, 5th and 6th months
measure: The rate of sputum Mtb negative conversion
timeFrame: the 2nd, 3rd, 5th and 6th months
measure: The time of sputum Mtb negative conversion
timeFrame: the 2nd, 3rd, 5th and 6th months
measure: Number of Patients With Adverse Events
timeFrame: 18 months (within one year of completion of therapy)
Other outcomes:
Locations:
city: Zhuhai
country: China
facility: The Fifth Affiliated Hospital Sun Yat-Sen University
state: Guangdong
Study officials:
affiliation: The Fifth Affiliated Hospital, Sun Yat-sen University
name: Li Ding, M.D
role: STUDY_DIRECTOR
affiliation: The Fifth Affiliated Hospital, Sun Yat-sen University
name: Yuanli Chen, M.Med
role: PRINCIPAL_INVESTIGATOR
affiliation: The Fifth Affiliated Hospital, Sun Yat-sen University
name: Xi Liu, M.D
role: PRINCIPAL_INVESTIGATOR
affiliation: The Fifth Affiliated Hospital, Sun Yat-sen University
name: JinYu Xia, M.Med
role: PRINCIPAL_INVESTIGATOR
affiliation: The Fifth Affiliated Hospital, Sun Yat-sen University
name: Zhongsi Hong, M.Med
role: PRINCIPAL_INVESTIGATOR
affiliation: The Fifth Affiliated Hospital, Sun Yat-sen University
name: Jian Liu, M.D
role: PRINCIPAL_INVESTIGATOR
affiliation: The Fifth Affiliated Hospital, Sun Yat-sen University
name: Minyi Lin, M.Med
role: PRINCIPAL_INVESTIGATOR
affiliation: The Fifth Affiliated Hospital, Sun Yat-sen University
name: Lisi Deng, M.Med
role: PRINCIPAL_INVESTIGATOR
affiliation: The Fifth Affiliated Hospital, Sun Yat-sen University
name: Lei Luo
role: PRINCIPAL_INVESTIGATOR
affiliation: The Fifth Affiliated Hospital, Sun Yat-sen University
name: Yayi Huang
role: PRINCIPAL_INVESTIGATOR
affiliation: The Fifth Affiliated Hospital, Sun Yat-sen University
name: Xiaoqing Luo
role: PRINCIPAL_INVESTIGATOR
affiliation: The Fifth Affiliated Hospital, Sun Yat-sen University
name: Yin Li
role: PRINCIPAL_INVESTIGATOR
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