NCT04187469

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

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

• Status: Unknown
• Phase: N/A
• Study type: Interventional
• Enrollment: 286 (estimated)
• Sponsor: Fifth Affiliated Hospital, Sun Yat-Sen University · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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).

Conditions

• Pulmonary Tuberculosis

Interventions

Type	Name	Description
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.

Timeline

• Start date: 2020-03-01
• Primary completion: 2023-02-01
• Completion: 2024-02-01
• First posted: 2019-12-05
• Last updated: 2019-12-05

Locations

1 site across 1 country: China