Innovating Shorter, All- Oral, Precised Treatment Regimen for Rifampicin Resistant Tuberculosis：BLMZ Chinese Cohort
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 120
- 试验地点
- 3
- 主要终点
- The proportion of participants with favorable outcome
研究概览
简要总结
The goal of this clinical trial is to learn if the all-oral, shorter-course BLMZ regimen can treat Rifampicin-Resistant Tuberculosis (RR-TB) in Chinese participants aged 12 years and older. The main questions it aims to answer are:
What is the proportion of participants with a favorable outcome at 18 months after starting the BLMZ regimen? What is the safety profile of the BLMZ regimen, as measured by the incidence of Grade 3 or higher adverse events and serious adverse events during the treatment period? This is a single-arm study, so there is no comparison group. Researchers will compare the study results to historical data to see if the BLMZ regimen shows sufficient efficacy and safety in the Chinese population.
Participants will:
Undergo screening tests to confirm eligibility, including tests for TB bacteria and drug resistance.
Receive the BLMZ regimen (Bedaquiline, Linezolid, Moxifloxacin/Levofloxacin, and Pyrazinamide) orally for 9 months.
Attend regular clinic visits for safety assessments, medication refills, and tests (e.g., sputum tests, blood tests, ECG, CT scans) during the 9-month treatment period and then every 3 months during a 15-month post-treatment follow-up period until 24 months after starting the treatment.
详细描述
Study Rationale and Background:
Tuberculosis (TB) remains a significant global health threat, with Rifampicin-Resistant TB (RR-TB) posing a particularly severe challenge due to prolonged treatment durations, high toxicity, and suboptimal success rates. While the standard of care in China has historically involved 18-20 month regimens, the World Health Organization (WHO) has recently endorsed shorter, all-oral regimens. The BLMZ regimen, composed of Bedaquiline (B), Linezolid (L), Moxifloxacin (M), and Pyrazinamide (Z), demonstrated high efficacy (89% favorable outcome) in the global endTB trial. However, prospective data on its application and performance in the Chinese population are lacking. This study aims to bridge this evidence gap by prospectively evaluating the efficacy, safety, and feasibility of the 9-month BLMZ regimen in a Chinese RR-TB cohort, thereby informing national policy and clinical practice.
Study Design:
This is a prospective, multicenter, single-arm, open-label, interventional study. The study employs a Bayesian statistical framework with a pre-specified success threshold to evaluate the primary efficacy endpoint. Historical data from the endTB study (BLMZ arm) will be incorporated using a power prior model to augment the statistical analysis, allowing for more robust inference with the planned sample size.
Intervention:
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
- 12 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •The participant (and their guardian if the participant lacks civil capacity) voluntarily signs the informed consent form (ICF) prior to enrollment.
- •The participant (and their guardian) indicates willingness to complete all steps and intervention periods of the study.
- •Male or female, aged ≥12 years, with a body weight ≥30 kilograms (kg).
- •Bacteriologically confirmed pulmonary tuberculosis, with molecular or phenotypic drug susceptibility testing (DST) results within the last 3 months confirming Rifampicin resistance and susceptibility to at least one of Moxifloxacin (MFX) or Levofloxacin (LFX).
- •Sputum or respiratory lavage fluid collected during the screening period is culture-positive for Mycobacterium tuberculosis, with DST results indicating Rifampicin resistance and susceptibility to at least one of MFX or LFX.
- •Females of childbearing potential are not pregnant (as confirmed by a negative pregnancy test), voluntarily agree to pregnancy testing, and are willing to use highly effective contraception from the time of ICF signing until 3 months after the end of study treatment.
- •For males of reproductive potential, use condoms or other methods to ensure effective contraception for their partner.
- •Females who are breastfeeding are willing to discontinue breastfeeding from the time of ICF signing until 3 months after the end of study treatment.
- •Voluntary acceptance of HIV testing; if the result is positive, voluntary acceptance of antiretroviral therapy.
排除标准
- •Previous treatment with any of the drugs Bedaquiline (BDQ) or Linezolid (LZD) for more than 30 days.
- •Concurrent hematogenous disseminated pulmonary tuberculosis or severe extrapulmonary tuberculosis as determined by the investigator.
- •Current use of medications prohibited by the study protocol, and the investigator judges that the priority of continuing said medication for patient benefit outweighs participation in this study.
- •（Note: If the investigator judges that the benefit of participating in this study is higher and obtains the participant's consent, the prohibited medication should be discontinued with an adequate washout period before participation.）
- •Known history of hypersensitivity to any drug in the protocol.
- •Current participation in any other investigational drug clinical trial.
- •Presence of cardiovascular disease risk at screening:
- •QTcF interval >450 milliseconds (ms). (Note: If QTcF >450 ms is detected, one unscheduled visit during the screening period is allowed for re-assessment.)
- •History of clinically significant arrhythmia within 60 days prior to enrollment, which in the investigator's opinion may increase risk upon study participation.
- •Decompensated heart failure.
- •Grade 3 hypertension not at control target.
- •Abnormal thyroid function.
- •Abnormal serum calcium, magnesium, or potassium levels. (Note: Isolated electrolyte disturbances without underlying disease may be considered for re-screening after corrective treatment.)
- •Other conditions deemed by the investigator to pose a cardiovascular disease risk.
- •History of optic neuropathy or peripheral neuropathy, which in the investigator's opinion may progress/worsen during the study or is unsuitable for study participation.
- •Evidence of liver disease at screening:
- •Active viral hepatitis: Positive HBsAg, or positive HBeAg and HBV DNA, or positive HCV RNA test, accompanied by persistent or recurrent abnormal ALT.
- •Decompensated cirrhosis.
- •History of renal disease or renal disease-related manifestations at screening:
- •History of unstable or rapidly progressive renal disease.
- •Moderate/severe renal impairment or end-stage renal disease (eGFR < 60 mL/min/1.73 m²).
- •Serum creatinine (Cr) ≥133 μmol/L (1.5 mg/dL) for males, or Cr ≥124 μmol/L (1.4 mg/dL) for females.
- •Other laboratory abnormalities at screening:
- •Hemoglobin level < 8.0 g/dL.
- •Platelet count <75,000 /mm³.
- •Absolute neutrophil count (ANC) <1000 /mm³.
- •Aspartate aminotransferase (AST) or Alanine aminotransferase (ALT) >3 times the upper limit of normal (ULN).
- •Total bilirubin >2 times ULN, or >1.5 times ULN accompanied by other abnormal liver enzymes.
- •Albumin <30 g/L.
- •Pregnant or breastfeeding.
- •Any other condition (e.g., severe psychiatric disorder, neurological condition, substance abuse) that, in the opinion of the investigator, would make the participant unsuitable for the study or unable to adhere to the protocol.
研究组 & 干预措施
Experimental arm
All enrolled participants will receive the all-oral, shorter-course BLMZ regimen for a total of 9 months from end-TB study, as described in the Intervention section.
干预措施: BLMZ (Drug)
结局指标
主要结局
The proportion of participants with favorable outcome
时间窗: 18 months after treatment initiation
Favorable Outcome: A participant is considered to have a favorable outcome if they do not meet any criteria for an unfavorable outcome, and they meet the following key criterion: two consecutive negative sputum cultures, with the final culture obtained between 16 and 18 months after treatment initiation. Unfavorable Outcome: An outcome is classified as unfavorable if any of the following occur: * Treatment failure (change of regimen). * Extended treatment beyond the protocol-defined period. * Bacteriological relapse or failure (positive culture at the end of the study period). * Death from any cause. * Loss to follow-up.
次要结局
- The proportion of participants with favorable outcome(24 months after treatment initiation)
- The proportion of participants with sputum conversion(2 months from treatment initiation)
- Time to sputum conversion(9 months after treatment initiation)
- the incidence of grade 3 or worse AEs and SAEs(24 months after treatment initiation)
研究者
Chu naihui
Professor
Beijing Chest Hospital