A Study on the Short-course Treatment Regimen Containing Pretomanid for Drug-resistant Tuberculosis
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 发起方
- 入组人数
- 200
- 主要终点
- Favorable outcomes during the treatment period
研究概览
简要总结
Rifampicin-resistant tuberculosis (RR-TB) is characterized by a long treatment course, high incidence of adverse reactions, low cure rate and high recurrence rate. This is related to the large number of drugs in the RR-TB treatment regimen, high incidence of adverse reactions and long treatment course, which leads to poor patient compliance. There is an urgent need for new, effective and safe short-course regimens for drug-resistant tuberculosis. A 6-month short-course oral regimen containing pretomanid was introduced in 2020. However, as pretomanid is not yet available in China, it has not been verified and promoted in China. Pretomanid is expected to be launched in China in 2025, and it is urgent to evaluate the application of the new short-course regimen containing pretomanid in the Chinese population. This study is a prospective, randomized, controlled clinical trial. It plans to include RR-TB patients aged ≥12 years in multiple domestic centers. Under the guidance of rapid molecular drug susceptibility test results, the experimental group will be treated with bedaquiline, pretomanid, linezolid and moxifloxacin for 6 months, while the control group will be treated with bedaquiline, delamanid, linezolid and levofloxacin or bedaquiline, delamanid, linezolid and clofazimine for 6 months, depending on the susceptibility to fluoroquinolones. For patients with unknown susceptibility to fluoroquinolones, bedaquiline, delamanid, linezolid, levofloxacin and clofazimine will be used for 6 months. The efficacy and safety will be evaluated to provide a basis for the introduction and implementation of new short-course regimens for RR-TB in China.
详细描述
Study Design Type This study is a prospective, randomized controlled trial aimed at evaluating the efficacy and safety of different treatment regimens for patients with drug-resistant tuberculosis (RR-TB).
Study Subjects Patients with MDR/RR-TB who meet the inclusion and exclusion criteria will be enrolled in this study. Deviation from the inclusion and exclusion criteria is not allowed as it may compromise the scientific integrity, regulatory acceptability, or safety of the study participants. Therefore, it is crucial to adhere to the criteria specified in the study protocol.
Study Population Study Population: Male or female patients aged ≥12 years, with newly diagnosed or retreated pulmonary tuberculosis, and no contraindications to the study drugs.
Planned Enrollment 200 cases, 100 cases in each group. Inclusion and Exclusion Criteria
Inclusion Criteria:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 12 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •he research participants themselves voluntarily signed the informed consent form before being enrolled; for those without full capacity for civil conduct, the consent form was signed by their legal guardians.
- •The research participants (and their guardians) indicated their willingness to complete all steps and intervention periods of the study.
- •Male or female, aged 12 years or older, weighing 30 kilograms or more. Confirmed cases of pulmonary tuberculosis pathogen, with molecular or phenotypic drug sensitivity results within the past 3 months confirming resistance to rifampicin, and confirmed by the pathogen culture results of sputum collected at the time of enrollment.
- •Fertile women not in pregnancy, voluntarily undergoing pregnancy tests, with negative results, and willing to use highly effective contraceptive measures from the time of signing the informed consent until 3 months after the end of the study treatment.
- •For fertile men, use condoms or other methods to ensure effective contraception for their sexual partners.
- •Women in lactation, willing to stop breastfeeding from the time of signing the informed consent until 3 months after the end of the study treatment.
- •Voluntary to undergo HIV testing. If the result is positive, voluntarily accept antiretroviral therapy.
排除标准
- •Had a known hypersensitivity reaction to any drug in the protocol. Was participating in any clinical trial of other drugs. At the screening stage, had cardiovascular disease risk: QTcF interval over 480 milliseconds; within 60 days before enrollment, had a history of clinically significant arrhythmia that the investigator considered could be clinically significant, and the investigator considered that participating in the study might increase the risk; decompensated heart failure; grade 3 hypertension and not reaching the control target; thyroid dysfunction; abnormal serum calcium, magnesium or potassium levels.
- •Had a history of optic nerve or peripheral nerve lesion, and the investigator considered that it might progress/deteriorate during the study or was not suitable for participating in this study.
- •At the screening stage, had the following liver disease manifestations: active viral hepatitis; decompensated stage of liver cirrhosis.
- •At the screening stage, had the following kidney disease history or kidney-related manifestations: unstable or rapidly progressive kidney disease history; moderate/severe renal function impairment or end-stage renal disease; male serum creatinine ≥ 133 μmol/L, female serum creatinine ≥ 124 μmol/L.
- •Other laboratory test abnormalities: hemoglobin level < 8.0 g/dL; platelet count < 75,000/mm³; absolute neutrophil count < 1000/mm³; aspartate aminotransferase (AST)/alanine aminotransferase (ALT) > 3×ULN; total bilirubin > 2×ULN, or > 1.5×ULN, combined with other liver enzyme abnormalities; albumin < 30 g/L.
- •The investigator considered that the study participants could not complete the study process, or participating in the study was unsafe for the study participants.
研究组 & 干预措施
test group
A six - month regimen containing bedaquiline (BDQ), pretomanid (Pa), linezolid (LZD), and moxifloxacin (MFX)
干预措施: bedaquiline (Drug)
test group
A six - month regimen containing bedaquiline (BDQ), pretomanid (Pa), linezolid (LZD), and moxifloxacin (MFX)
干预措施: Pretomanid (Pa) (Drug)
test group
A six - month regimen containing bedaquiline (BDQ), pretomanid (Pa), linezolid (LZD), and moxifloxacin (MFX)
干预措施: linezolid (Drug)
test group
A six - month regimen containing bedaquiline (BDQ), pretomanid (Pa), linezolid (LZD), and moxifloxacin (MFX)
干预措施: Moxifloxacin (M) (Drug)
Control group (Group A)
The control group was stratified according to the drug susceptibility results of fluoroquinolones (FQs). The FQs - sensitive group was treated with the BDLL regimen (bedaquiline (BDQ), delamanid (DLM), linezolid (LZD), and levofloxacin (LFX)), the FQs - resistant group was treated with the BDLC regimen (BDQ, DLM, LZD, and clofazimine (CFZ)), and the group with unknown drug susceptibility was treated with the BDLLfxC regimen (BDQ, DLM, LZD, LFX, and CFZ). The duration of all regimens was 6 months.
干预措施: bedaquiline (Drug)
Control group (Group A)
The control group was stratified according to the drug susceptibility results of fluoroquinolones (FQs). The FQs - sensitive group was treated with the BDLL regimen (bedaquiline (BDQ), delamanid (DLM), linezolid (LZD), and levofloxacin (LFX)), the FQs - resistant group was treated with the BDLC regimen (BDQ, DLM, LZD, and clofazimine (CFZ)), and the group with unknown drug susceptibility was treated with the BDLLfxC regimen (BDQ, DLM, LZD, LFX, and CFZ). The duration of all regimens was 6 months.
干预措施: linezolid (Drug)
Control group (Group A)
The control group was stratified according to the drug susceptibility results of fluoroquinolones (FQs). The FQs - sensitive group was treated with the BDLL regimen (bedaquiline (BDQ), delamanid (DLM), linezolid (LZD), and levofloxacin (LFX)), the FQs - resistant group was treated with the BDLC regimen (BDQ, DLM, LZD, and clofazimine (CFZ)), and the group with unknown drug susceptibility was treated with the BDLLfxC regimen (BDQ, DLM, LZD, LFX, and CFZ). The duration of all regimens was 6 months.
干预措施: Delamanid (D) (Drug)
Control group (Group A)
The control group was stratified according to the drug susceptibility results of fluoroquinolones (FQs). The FQs - sensitive group was treated with the BDLL regimen (bedaquiline (BDQ), delamanid (DLM), linezolid (LZD), and levofloxacin (LFX)), the FQs - resistant group was treated with the BDLC regimen (BDQ, DLM, LZD, and clofazimine (CFZ)), and the group with unknown drug susceptibility was treated with the BDLLfxC regimen (BDQ, DLM, LZD, LFX, and CFZ). The duration of all regimens was 6 months.
干预措施: Levofloxacin (Drug)
Control group (Group A)
The control group was stratified according to the drug susceptibility results of fluoroquinolones (FQs). The FQs - sensitive group was treated with the BDLL regimen (bedaquiline (BDQ), delamanid (DLM), linezolid (LZD), and levofloxacin (LFX)), the FQs - resistant group was treated with the BDLC regimen (BDQ, DLM, LZD, and clofazimine (CFZ)), and the group with unknown drug susceptibility was treated with the BDLLfxC regimen (BDQ, DLM, LZD, LFX, and CFZ). The duration of all regimens was 6 months.
干预措施: clofazimine (Drug)
结局指标
主要结局
Favorable outcomes during the treatment period
时间窗: From the initiation of treatment until the 28th week.
Cure: Completing 80% or more of the medication dosage as required by the protocol within 28 weeks after the start of the research treatment, with no evidence of treatment failure, and the Mycobacterium tuberculosis (MTB) cultures of the last two sputum specimens (collection interval ≥ 14 days) at the end of treatment being negative. Treatment completion: Completing more than 80% of the medication dosage as required by the protocol within 28 weeks after the start of the research treatment, with no evidence of treatment failure, but without evidence that the MTB cultures of two sputum specimens collected at an interval of at least 14 days are negative.
次要结局
- Favorable outcomes during the follow - up period after treatment(From the beginning of the treatment until 72 weeks.)
- Favorable outcomes with an extended follow - up period(Follow - up was conducted until 108 weeks after enrollment.)
- Unfavorable outcome(From the time of enrollment until the 108th week of follow - up)
研究者
Yan Hu
Wuhan Pulmonary hospital
Wuhan Pulmonary Hospital