innovating shorter, all- oral, precised treatment regimen for rifampicin resistant tuberculosis：bdll chinese cohort

Conditions: Drug-resistant Tuberculosis; Pulmonary Tuberculosis; Rifampin-resistant Tuberculosis

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 \ 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.

Keywords: drug-resistant tuberculosis bdll chinese population short regimen