Innovating Shorter, All- Oral, Precised Treatment Regimen for Rifampicin Resistant Tuberculosis：BDLL Chinese Cohort
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 120
- 试验地点
- 34
- 主要终点
- Proportion of participants with favorable outcomes in both treatment and follow-up period
研究概览
简要总结
This is an investigational, prospective, multicenter, single-arm, open label trial. The goal of this clinical trial is to evaluate the efficacy and safety of a 6-month all-oral regimen, consisting of Bedaquiline (BDQ, B), Delamanid (DLM, D), Linezolid (LZD, L), Levofloxacin (LFX) or Clofazimine (CFZ, C), or BDLLfxC regimen, to treat rifampin-resistant pulmonary tuberculosis (RR-TB) in Chinese teenagers and adults (aged 12 years or above). The main questions it aims to answer are:
- Is BDLLfxC regimen effective to treat RR-TB in Chinese participants?
- Is BDLLfxC regimen safe in Chinese RR-TB participants? Participants will take BDLLfxC regimen to treat their RR-TB. There will be no additional hospital visits, laboratory tests or radiological examinations other than routine clinical practice.
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
- •Participants are willing to sign informed consent of this trial, those without capacity for civil conduct need their legal guardian to sign
- •Participants (and their legal guardian if applicable) are willing to cooperate to complete all trial procedures
- •Male or female, 12 years or older, weight ≥ 30kg
- •Confirmed pulmonary tuberculosis with resistance to rifampin by phenotypic or genotypic susceptibility testing within 3 months, and must be re-confirmed by sputum culture sampled at trial inclusion
- •Women with childbearing potential should not be pregnant, confirmed by a volunteered negative pregnancy test, and are willing to use effective contraceptive method from giving consent to 3 months after study treatment
- •Men with childbearing potential must be willing to use condom or other effective contraceptive methods to avoid their sex partners from being pregnant
- •Women in breastfeeding period must be willing to discontinue breastfeeding from giving consent to 3 months after study treatment
- •Participants are willing to take HIV test, and willing to take appropriate antiretroviral therapy if positive
排除标准
- •Previously use of Bedaquiline or Delamanid for at least 28 days
- •Concomitant hematogenous disseminated tuberculosis, or severe pulmonary tuberculosis in investigator's opinion (including tuberculosis of the digestive system, osteoarticular tuberculosis or tuberculous meningitis)
- •Currently using any drug that has been prohibited in the protocol
- •History of allergic action to any of the study drugs
- •Currently participating in any other clinical trials
- •Cardiovascular risk at screening: (1) QTcF more than 480 milliseconds (ms); (2) History of clinically significant arrythmia, and at investigator's opinion, participation in this study will increase the risk; (3) Decompensated heart failure; (4) Grade 3 high blood pressure and the goals of treatment have not been reached; (5) Abnormal thyroid function; (6) Abnormal serum Ca, Mg or K level; (7) Other conditions with cardiovascular risks in investigator's opinion.
- •History of optic neuropathy or peripheral neuropathy, and the investigator considers that the condition may progress or deteriorate by participating in the study, or inappropriate to participate
- •Hepatic disorders at screening: (1) Active viral hepatitis: HBsAg positive or HBV DNA >1000 CPs/mL, with elevated AST or ALT or HCV RNA positive; (2) Decompensated cirrhosis
- •Renal disorders at screening: (1) Unstable or rapidly progressive renal disease; (2) Moderate / severe renal disfunction or end-stage renal disease (eGFR< 60 mL/min/1.73 m2); (3) Serum creatinine ≥133 μmol/L(1.5 mg/mL) in men, or ≥124 μmol/L (1.4 mg/mL) in women
- •Other abnormal laboratory test: (1) Hemoglobin < 8.0g/dL; (2) Platelet <75,000/mm3; (3) Absolute neutrophil count <1000/mm3; (4) Aspartate transaminase (AST) or alanine aminotransferase (ALT) >3×upper limit of normal (ULN); (5) Total bilirubin (TBil) >2×ULN, or >1.5×ULN together with abnormal AST or ALT; (6) Albumin <30g/L
- •The investigator considers that the participant is not able to complete the study process, or the participation is not safe.
研究组 & 干预措施
BDLL
6-month all-oral regimen, consisting of Bedaquiline (BDQ, B), Delamanid (DLM, D), Linezolid (LZD, L), Levofloxacin (LFX) or Clofazimine (CFZ, C), as known as BDLLfxC or BDLL regimen
干预措施: bedaquiline (Drug)
BDLL
6-month all-oral regimen, consisting of Bedaquiline (BDQ, B), Delamanid (DLM, D), Linezolid (LZD, L), Levofloxacin (LFX) or Clofazimine (CFZ, C), as known as BDLLfxC or BDLL regimen
干预措施: delamanid (Drug)
BDLL
6-month all-oral regimen, consisting of Bedaquiline (BDQ, B), Delamanid (DLM, D), Linezolid (LZD, L), Levofloxacin (LFX) or Clofazimine (CFZ, C), as known as BDLLfxC or BDLL regimen
干预措施: linezolid (Drug)
BDLL
6-month all-oral regimen, consisting of Bedaquiline (BDQ, B), Delamanid (DLM, D), Linezolid (LZD, L), Levofloxacin (LFX) or Clofazimine (CFZ, C), as known as BDLLfxC or BDLL regimen
干预措施: Levofloxacin (Drug)
BDLL
6-month all-oral regimen, consisting of Bedaquiline (BDQ, B), Delamanid (DLM, D), Linezolid (LZD, L), Levofloxacin (LFX) or Clofazimine (CFZ, C), as known as BDLLfxC or BDLL regimen
干预措施: Clofazimine (Drug)
结局指标
主要结局
Proportion of participants with favorable outcomes in both treatment and follow-up period
时间窗: Up to 72 weeks after start of treatment
Favorable outcome in treatment period (up to 28 weeks after start of treatment): a participant's outcome will be defined as "favorable" if it meets any of the following below and has not been defined as "unfavorable" before, 1. . Cured: complete at least 80% of total required dose per protocol, with negative culture results of last two sputum samples (collected 14 days apart) ; 2. . Treatment completed: complete at least 80% of total required dose per protocol, with NO negative culture results of last two sputum samples (collected 14 days apart); Favorable outcome in follow-up period (from end of treatment to 72 weeks after start of treatment): a participant's outcome will be defined as "favorable" if it meets any of the following below and has not been defined as "unfavorable" before, (1). Cured: sputum culture negative at 72 weeks from start of treatment; (2). Culture negative when last seen: loss to follow-up before 72 weeks, with negative sputum culture when last seen.
次要结局
- Proportion of participants with grade 3 or 4 adverse effect(Up to 72 weeks after start of treatment)
- Proportion of participants with favorable outcomes in treatment period, follow-up period and prolonged follow-up period, respectively(Up to 108 weeks after start of treatment)
- Time to culture conversion(Up to 72 weeks after start of treatment)
研究者
Wen-hong Zhang
Head of Infectious Disease Department
Huashan Hospital