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.
Full Title of Study: “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
- Study Design
- Allocation: Randomized
- Intervention Model: Parallel Assignment
- Primary Purpose: Treatment
- Masking: None (Open Label)
- Study Primary Completion Date: February 1, 2023
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).
- 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.
- 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.
Arms, Groups and Cohorts
- Experimental: Regimen 1: 2HRM/4HR
- Two month of chemotherapy with Moxifloxacin, Isoniazid and Rifampicin, followed by four month of Isoniazid and Rifampicin only.
- 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.
Clinical Trial Outcome Measures
- 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.
- 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 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 time of sputum Mtb negative conversion
- Time Frame: the 2nd, 3rd, 5th and 6th months
- The first time of sputum Mtb negative conversion
- 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.
Participating in This Clinical Trial
- 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.
Gender Eligibility: All
Minimum Age: 18 Years
Maximum Age: N/A
Are Healthy Volunteers Accepted: No
- Lead Sponsor
- Fifth Affiliated Hospital, Sun Yat-Sen University
- Provider of Information About this Clinical Study
- Principal Investigator: Li Ding, Associate chief physician of infectious diseases – Fifth Affiliated Hospital, Sun Yat-Sen University
- Overall Official(s)
- Li Ding, M.D, Study Director, The Fifth Affiliated Hospital Sun Yat-Sen University
- Yuanli Chen, M.Med, Principal Investigator, The Fifth Affiliated Hospital Sun Yat-Sen University
- Xi Liu, M.D, Principal Investigator, The Fifth Affiliated Hospital Sun Yat-Sen University
- JinYu Xia, M.Med, Principal Investigator, The Fifth Affiliated Hospital Sun Yat-Sen University
- Zhongsi Hong, M.Med, Principal Investigator, The Fifth Affiliated Hospital Sun Yat-Sen University
- Jian Liu, M.D, Principal Investigator, The Fifth Affiliated Hospital Sun Yat-Sen University
- Minyi Lin, M.Med, Principal Investigator, The Fifth Affiliated Hospital Sun Yat-Sen University
- Lisi Deng, M.Med, Principal Investigator, The Fifth Affiliated Hospital Sun Yat-Sen University
- Lei Luo, Principal Investigator, The Fifth Affiliated Hospital Sun Yat-Sen University
- Yayi Huang, Principal Investigator, The Fifth Affiliated Hospital Sun Yat-Sen University
- Xiaoqing Luo, Principal Investigator, The Fifth Affiliated Hospital Sun Yat-Sen University
- Yin Li, Principal Investigator, The Fifth Affiliated Hospital Sun Yat-Sen University
- Overall Contact(s)
- Li Ding, M.D, 13926921192, firstname.lastname@example.org
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