A Short Regimen for Patients With Rifampicin-resistant Isoniazid-susceptible Tuberculosis
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 入组人数
- 100
- 主要终点
- the proportion of patients with a favourable outcome at 12 months (53 weeks) post treatment initiation
研究概览
简要总结
To assess outcome of treatment and safety among patients with rifampicin-resistant isoniazid-susceptible pulmonary tuberculosis treated with a novel regimen consisting of isoniazid, bedaquiline, and moxifloxacin throughout for 6 months, supplemented by pyrazinamide for the initial 2 months.
详细描述
Rifampicin-resistant tuberculosis (RR-TB) could be classified into rifampicin-resistant, isoniazid-susceptible TB (RrHs-TB) and rifampicin-resistant, isoniazid-resistant TB (MDR-TB), that is MDR-TB. RrHs-TB and MDR-TB are different because isoniazid has potent early bactericidal activity (EBA) and remains susceptible in RrHs-TB.
The standard first line anti-TB regimen recommended by WHO consisting of isoniazid and rifampicin throughout for 6 months supplemented by pyrazinamide and ethambutol for the initial 2 months (2HRZE/4HR). The duration of treatment of the first line standard 6-month regimen is mainly determined by the sterilization power of the core drug, namely rifampicin, paired with pyrazinamide. Moxifloxacin had potent EBA that is comparable to that of isoniazid. Bedaquiline has delayed onset of action but after a few days of treatment its EBA is comparable to that of isoniazid and rifampicin. Both moxifloxacin and bedaquiline have potent sterilizing activity.
To avoid the use of a toxic MDR-TB regimen, we hypothesize that the combination of bedaquiline and moxifloxacin is non inferior to rifampicin in terms of EBA and sterilizing activity, and could be used to substitute for rifampicin in the standard first line anti-TB regimen (2HRZE/4HR) as a novel approach for the treatment of RrHs-TB, as well as TB patients for whom rifamycin is intolerable (Ri-TB) and TB patients for whom rifamycin-sparing anti-TB regimens are preferred due to drug-drug interaction (Rs-TB).
Trial intervention
The novel regimen will be given in two phases:
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •A patient will be eligible for entry to the study if he/she:
- •Is willing and able to give informed consent to be enrolled in the trial treatment and follow-up (signed or witnessed consent if the patient is illiterate)
- •Is aged 18 years or older
- •Has bacteriologically-confirmed pulmonary tuberculosis by Xpert MTB/RIF, other nucleic acid amplification test, or culture
- •With initial laboratory result of resistance to rifampicin by Xpert MTB/RIF or Xpert MTB/RIF ultra, or other DST (line probe assay, culture); and with initial laboratory result that is susceptible to isoniazid by Xpert MTB/RIF or other DST. If rifampicin resistance is detected by Xpert MTB/RIF or Xpert MTB/RIF ultra in specimens with very low bacillary, rifampicin resistance has been confirmed by a repeat molecular test.
- •With initial laboratory result of being susceptible to rifampicin by Xpert MTB/RIF or other DST (Xpert MTB/RIF ultra, line probe assay, culture) but are not able to tolerate rifampicin for whom rifabutin is intolerable or clinically not indicated; and with initial laboratory result that is susceptible to isoniazid by Xpert MTB/RIF or other DST
- •With initial laboratory result of being susceptible to rifampicin by Xpert MTB/RIF or other DST (Xpert MTB/RIF ultra, line probe assay, culture) but rifamycin-sparing regimens are preferred due to drug-drug interaction, such as organ transplant recipients; and with initial laboratory result that is susceptible to isoniazid by Xpert MTB/RIF or other DST.
- •With initial laboratory result that is susceptible to fluoroquinolone by Xpert MTB/XDR or other DST.
- •If HIV test positive, is willing to be treated with ART in accordance with the national policies.
- •Agrees to use effective barrier contraception or have an intrauterine contraceptive device during treatment phase if a pre-menopausal woman
- •Has an identifiable address and expects to remain in the area for the duration of the study
- •Is willing to adhere to the follow-up schedule and to study procedures
排除标准
- •A patient will not be eligible for entry to the study if he/she:
- •Is infected with a strain of M. Tuberculosis resistant to isoniazid by Xpert MTB/XDR or other tests
- •Is infected with a strain of M. Tuberculosis resistant to fluoroquinolone by Xpert MTB/XDR or other tests
- •Is infected with a strain of M. Tuberculosis resistant to amikacin by Xpert MTB/XDR or other tests and have no result of susceptibility of isoniazid by conventional drug susceptibility testing
- •Has tuberculous meningitis or bone and joint tuberculosis
- •Is critically ill, and in the judgment of the investigator, unlikely to survive more than 4 months.
- •Is known to be pregnant or breast-feeding
- •Is unable to attend or comply with treatment or follow-up schedule
- •Is unable to take oral medication
- •Has AST or ALT >5 times the upper limit of normal
- •Has AST or ALT > 3 times the upper limit of normal ,and either with symptoms of hepatitis or bilirubin > 1.5 times the upper limit of normal
- •Has any condition (social or medical) which in the opinion of the investigator would make study participation unsafe.
- •Is taking any medications contraindicated with the medicines in either the trial or control regimen
- •Has a known allergy to any fluoroquinolone antibiotic
- •Is currently taking part in another trial of a medicinal product
- •Has a QTcF interval of ≥450msec at screening
结局指标
主要结局
the proportion of patients with a favourable outcome at 12 months (53 weeks) post treatment initiation
时间窗: 12 months after treatment initiation
The primary efficacy outcome measure is the proportion of patients with a favourable outcome at 12 months (53 weeks) post treatment initiation
the proportion of patients experiencing a grade 3 or greater adverse event during treatment and follow-up to 12 months (53 weeks) post treatment initiation.
时间窗: from treatment initiation to 12 months after treatment initiation
The primary safety outcome measure is the proportion of patients experiencing a grade 3 or greater adverse event, as defined by the CTCAE criteria except hyperuricemia which will be defined by the DAIDS criteria, during treatment and follow-up to 12 months (53 weeks) post treatment initiation.
次要结局
- Time to unfavourable efficacy outcome(through study completion, an average of 9 months)
- the proportion of patients with a favourable outcome at 24 months (105 weeks) post treatment initiation(from treatment initiation to 24 months after treatment initiation)
- mortality during treatment and follow-up(from treatment initiation to 24 months after treatment initiation)
- Sputum conversion(through study completion, an average of 9 months)
- Change of regimen for adverse drug reactions(through study completion, an average of 9 months)
- Number of adverse drug reactions(through study completion, an average of 9 months)
- Proportion of patients with treatment interruption for 2 months(through study completion, an average of 9 months)
研究者
Chen-Yuan Chiang
Vice superintendent
Taipei Medical University WanFang Hospital