Clinical trial NCT06649721: Innovating Shorter, All- Oral, Precised Treatment Regimen for Rifampicin Resistant Tuberculosis：BDLL Chinese Cohort
Official title: Innovating Shorter, All- Oral, Precised Treatment Regimen for Rifampicin Resistant Tuberculosis：BDLL Chinese Cohort
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Drug-resistant Tuberculosis
Pulmonary Tuberculosis
Rifampin-resistant Tuberculosis
Keywords: Drug-resistant tuberculosis
BDLL
Chinese Population
Short regimen
Lead sponsor: Huashan Hospital
Sponsor class: OTHER
Collaborators: name: Beijing Chest Hospital
First posted: 2024-10-21
Enrollment: 120
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Proportion of participants with favorable outcomes in both treatment and follow-up period
timeFrame: Up to 72 weeks after start of treatment
Secondary outcomes:
measure: Proportion of participants with grade 3 or 4 adverse effect
timeFrame: Up to 72 weeks after start of treatment
measure: Proportion of participants with favorable outcomes in treatment period, follow-up period and prolonged follow-up period, respectively
timeFrame: Up to 108 weeks after start of treatment
measure: Time to culture conversion
timeFrame: Up to 72 weeks after start of treatment
Other outcomes:
Locations:
city: Hefei
country: China
facility: Anhui Chest Hospital
state: Anhui
city: Beijing
country: China
facility: The 8th Medical Center of Chinese PLA General Hospital
state: Beijing
city: Xiamen
country: China
facility: The First Affiliated Hospital of Xiamen University
state: Fujian
city: Nanning
country: China
facility: The Fourth People's Hospital of Nanning
state: Guangxi
city: Liupanshui
country: China
facility: Liupanshui Third People's Hospital
state: Guizhou
city: Shijiazhuang
country: China
facility: Hebei Chest Hospital
state: Hebei
city: Shijiazhuang
country: China
facility: The Fifth Hospital of Shijiazhuang
state: Hebei
city: Harbin
country: China
facility: Infectious Disease Hospital of Heilongjiang Province
state: Heilongjiang
city: Jiamusi
country: China
facility: Jiamusi Tuberculosis Hospital(Jiamusi Cancer Hospital)
state: Heilongjiang
city: Harbin
country: China
facility: Harbin Chest Hospital
state: Helongjiang
city: Luoyang
country: China
facility: Luoyang Center Hospital
state: Henan
city: Xinxiang
country: China
facility: The First Affiliated Hospital of Xinxiang Medical University
state: Henan
city: Zhengzhou
country: China
facility: Henan Chest Hospital
state: Henan
city: Zhengzhou
country: China
facility: Henan Infectious Disease Hospital
state: Henan
city: Wuhan
country: China
facility: Wuhan Pulmonary Hospital，Wuhan Tuberculosis Prevention and Control Institute
state: Hubei
city: Changsha
country: China
facility: Changsha Central Hospital
state: Hunan
city: Hulunbuir
country: China
facility: Hulunbuir Infectious Disease Hospital
state: Inner Mongolia
city: Nanjing
country: China
facility: The Second Hospital of Nanjing
state: Jiangsu
city: Nanchang
country: China
facility: Jiangxi Chest Hospital
state: Jiangxi
city: Changchun
country: China
facility: Infectious Disease Hospital of Changchun
state: Jilin
city: Jilin
country: China
facility: Jilin Tuberculosis Hospital
state: Jilin
city: Shenyang
country: China
facility: Shenyang Chest Hospital
state: Liaoning
city: Xi'An
country: China
facility: Xi'an Chest Hospital
state: Shaanxi
city: Jinan
country: China
facility: Shandong Public Health Clinical Center, Shandong University
state: Shandong
city: Linyi
country: China
facility: Linyi People Hospital
state: Shandong
city: Qingdao
country: China
facility: Qingdao Chest Hospital
state: Shandong
city: Weifang
country: China
facility: Weifang No.2 People's Hospital
state: Shandong
city: Yantai
country: China
facility: Yantai Qishan Hospital
state: Shandong
city: Taiyuan
country: China
facility: Shanxi Medical University Affiliated Chest Hospital
state: Shanxi
city: Chengdu
country: China
facility: Public Health Clinical Center of Chengdu
state: Sichuan
city: Tianjin
country: China
facility: Tianjin Haihe Hospital
state: Tianjin
city: Wenzhou
country: China
facility: Wenzhou Central Hospital
state: Zhejiang
city: Beijing
country: China
facility: Beijing Chest Hospital
city: Shanghai
country: China
facility: Huashan Hospital
Study officials:
References: