Innovating Shorter, All- Oral, Precised Treatment Regimen for Rifampicin Resistant Tuberculosis：BDLL Chinese Cohort
- Conditions
- Drug-resistant TuberculosisPulmonary TuberculosisRifampin-resistant Tuberculosis
- Interventions
- Registration Number
- NCT06649721
- Lead Sponsor
- Huashan Hospital
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 120
- 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
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description BDLL bedaquiline 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 BDLL delamanid 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 BDLL linezolid 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 BDLL Levofloxacin 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 BDLL Clofazimine 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
- Primary Outcome Measures
Name Time Method Proportion of participants with favorable outcomes in both treatment and follow-up period 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.
- Secondary Outcome Measures
Name Time Method Proportion of participants with grade 3 or 4 adverse effect Up to 72 weeks after start of treatment Adverse effect will be graded using Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1.
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 The definitions of favorable outcome in treatment and follow-up period are as described in primary outcome. Favorable outcome in prolonged follow-up period (from end of treatment to 108 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 108 weeks from start of treatment; (2). Culture negative when last seen: loss to follow-up before 108 weeks, with negative sputum culture when last seen.
Time to culture conversion Up to 72 weeks after start of treatment Time from start of treatment to the first time that obtained two consecutive negative sputum culture results, and the sputum samples must be collected 14 days apart. The date when first sputum sample is collected will be recorded as the date for culture conversion.
Trial Locations
- Locations (34)
The Fifth Hospital of Shijiazhuang
🇨🇳Shijiazhuang, Hebei, China
Wenzhou Central Hospital
🇨🇳Wenzhou, Zhejiang, China
Beijing Chest Hospital
🇨🇳Beijing, China
Luoyang Center Hospital
🇨🇳Luoyang, Henan, China
Anhui Chest Hospital
🇨🇳Hefei, Anhui, China
The 8th Medical Center of Chinese PLA General Hospital
🇨🇳Beijing, Beijing, China
The First Affiliated Hospital of Xiamen University
🇨🇳Xiamen, Fujian, China
The Fourth People's Hospital of Nanning
🇨🇳Nanning, Guangxi, China
Liupanshui Third People's Hospital
🇨🇳Liupanshui, Guizhou, China
Hebei Chest Hospital
🇨🇳Shijiazhuang, Hebei, China
Infectious Disease Hospital of Heilongjiang Province
🇨🇳Harbin, Heilongjiang, China
Jiamusi Tuberculosis Hospital(Jiamusi Cancer Hospital)
🇨🇳Jiamusi, Heilongjiang, China
Harbin Chest Hospital
🇨🇳Harbin, Helongjiang, China
The First Affiliated Hospital of Xinxiang Medical University
🇨🇳Xinxiang, Henan, China
Changsha Central Hospital
🇨🇳Changsha, Hunan, China
Henan Chest Hospital
🇨🇳Zhengzhou, Henan, China
Henan Infectious Disease Hospital
🇨🇳Zhengzhou, Henan, China
Wuhan Pulmonary Hospital，Wuhan Tuberculosis Prevention and Control Institute
🇨🇳Wuhan, Hubei, China
Hulunbuir Infectious Disease Hospital
🇨🇳Hulunbuir, Inner Mongolia, China
The Second Hospital of Nanjing
🇨🇳Nanjing, Jiangsu, China
Jiangxi Chest Hospital
🇨🇳Nanchang, Jiangxi, China
Infectious Disease Hospital of Changchun
🇨🇳Changchun, Jilin, China
Jilin Tuberculosis Hospital
🇨🇳Jilin, Jilin, China
Shenyang Chest Hospital
🇨🇳Shenyang, Liaoning, China
Xi'an Chest Hospital
🇨🇳Xi'An, Shaanxi, China
Shandong Public Health Clinical Center, Shandong University
🇨🇳Jinan, Shandong, China
Linyi People Hospital
🇨🇳Linyi, Shandong, China
Qingdao Chest Hospital
🇨🇳Qingdao, Shandong, China
Weifang No.2 People's Hospital
🇨🇳Weifang, Shandong, China
Yantai Qishan Hospital
🇨🇳Yantai, Shandong, China
Shanxi Medical University Affiliated Chest Hospital
🇨🇳Taiyuan, Shanxi, China
Public Health Clinical Center of Chengdu
🇨🇳Chengdu, Sichuan, China
Tianjin Haihe Hospital
🇨🇳Tianjin, Tianjin, China
Huashan Hospital
🇨🇳Shanghai, China