Clinical trial NCT06081361: Innovating Shorter, All- Oral, Precised, Individualized Treatment Regimen for Rifampicin Resistant Tuberculosis：Contezolid, Delamanid and Bedaquiline Cohort
Official title: A Multicenter, Randomized, Open-Label Study To Evaluate The Efficacy And Safety Of A Contezolid, Delamanid and Bedaquiline-Containing Short Regimen For The Treatment Of Rifampicin-Resistant Pulmonary Tuberculosis
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Pulmonary Tuberculosis
Rifampicin-resistant Tuberculosis
Keywords: tuberculosis
Rifampicin-resistant
short regimen
contezolid
delamanid
Lead sponsor: Beijing Chest Hospital
Sponsor class: OTHER
Collaborators: name: National Medical Center for Infectious Diseases
First posted: 2023-10-13
Enrollment: 186
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The goal of this clinical trial is to compare the efficacy and safety of a Contezolid and Delamanid-Containing short regimen to standard longer regimen in Rifampicin-resistant pulmonary tuberculosis (RR-TB). The main questions it aims to answer are:

* Is the efficacy of short regimen non-inferior to standard regimen?
* Is the short regimen safe enough to replace the standard regimen?

Participants will:

* Be given with either short or standard regimen for RR-TB treatment
* Be asked to complete the scheduled visit as planned.


Eligibility criteria: Inclusion criteria:

1. Age ≥18y and \<70y when signing informed consent;
2. Initial or re-treatment for pulmonary tuberculosis with:

1) MTB positive in sputum or bronchoalveolar lavage fluid culture at or within 3 months before screening, or MTB positive in molecular test at or within 3 months before screening, and; 2) recorded Rifampicin-resistance at or before screening; 3. Imaging (Chest X-ray or CT scan) proved pulmonary tuberculosis within 1 year before screening; 4. Never used BDQ, DLM or CZD, or the accumulative duration of any of the treatment is not more than 2 weeks 5. For women in childbearing age, negative in pregnancy test and effective contraceptive measures throughout study is required; 6. For men, effective contraceptive measures is required; 7. Willing to participate the study and sign informed consent.

Exclusion criteria:

1. The participant will be excluded by investigator based on the medical history or concomitant diseases such as serious metabolic disease, cardiovascular disease, hepatobiliary disease, renal disease, autoimmune disease, neuropsychiatric disorders, hematological disease, malignant neoplastic disease and so on; or the study will have negative impact on the well-being of the participant, or the participant is considered unable to complete the evaluation by investigator;
2. History of alcohol or drug abuse that the study is considered have negative impact on the well-being of the participant by investigator;
3. HIV positive;
4. Chronic hepatitis with HBsAg, HBeAg and anti-HBC antibody positive, or HBV-DNA\>1000 CPs/mL with rising ALT/AST;
5. Allergic to or known hypersensitive to any of study drugs;
6. Extensive (or advanced) pulmonary TB disease: presence of bilateral cavitary disease or extensive parenchymal damage on chest radiography;
7. Hematogenous disseminated pulmonary tuberculosis and serious extrapulmonary tuberculosis (such as tuberculosis in digestive system, urogenital system, osteoarticular tuberculosis, tuberculous meningitis);
8. With any of following risk factors for cardiovascular disease: 1) history of arrhythmia and on consequential treatment; 2) QTcF\>500ms on ECG; 3) history of ventricular arrhythmia; 4) torsade de pointe with heart failure, hypokalemia or familial long Q-T syndrome; 5) other possible risk factor for arrythmia;
9. Previous or current optic nerve disorder that may progress or deteriorate during the study by investigator's consideration;
10. Was enrolled within 2 months before screening, or currently in other studies; except for those who participating observational study or in the post-treatment period;
11. Being considered unlikely to survive for more than 6 months by investigator;
12. BMI \< 17kg/m2
13. May need surgical procedures based on the evaluation of pulmonary lesions;
14. May continuous use prohibited concomitant medications that is considered not suitable for the study by investigator;
15. Positive in pregnancy test or known pregnancy, breastfeeding, or plan to become pregnant during or within 6 months after the study treatment;
16. Abnormal laboratory test results: 1) Plasma potassium lower than lower limit of normal (LLN); 2) Hb \< 8.0 g/dL； 3) platelet count \<75,000/mm3； 4) WBC count\<3000/mm3； 5）AST/ALT \>3×ULN； 6）creatinine\>2×ULN；7）total bilirubin\>2×ULN, or \>1.5×ULN，with abnormal AST or ALT; 8) Albumin \< 30g/L

Primary outcomes:
measure: Favourable outcome rate at 24 months after randomization
timeFrame: from randomization to 24 months after
Secondary outcomes:
measure: Unfavourable outcome rate at 24 months after randomization
timeFrame: from randomization to 24 months after
measure: Time to culture conversion
timeFrame: from randomization to 24 months after
measure: Grade 3 or higher adverse event rate
timeFrame: from randomization to 24 months after
Other outcomes:
measure: Contezolid plasma concentration
timeFrame: 7d±3d after the first dose of contezolid
Locations:
city: Beijing
country: China
facility: Beijing Chest Hospital affiliated to Capital Medical University
state: Beijing
city: Shijiazhuang
country: China
facility: Hebei Chest Hospital
state: Hebei
city: Harbin
country: China
facility: Harbin Chest Hospital
state: Heilongjiang
city: Hulunbuir
country: China
facility: Infectious Disease Hospital of Hulunbuir
state: Inner Mongolia
city: Qingdao
country: China
facility: Qingdao Chest Hospital
state: Shandong
city: Taiyuan
country: China
facility: Taiyuan Fourth People's Hospital
state: Shanxi
city: Beijing
country: China
facility: The 8th Medical Center of Chinese Pla General Hospital
city: Changsha
country: China
facility: Changsha Central Hospital
city: Changsha
country: China
facility: Hunan Province Chest Hospital
city: Chongqing
country: China
facility: Chongqing Public Heath Treatment Center
city: Dalian
country: China
facility: Dalian Public Health Center
city: Fuzhou
country: China
facility: Fuzhou Pulmonary Hospital of Fujian
city: Guangzhou
country: China
facility: Guangzhou Chest Hospital
city: Haerbin
country: China
facility: Heilongjiang Province center for tuberculosis Control and Prevention
city: Haikou
country: China
facility: Second Affiliated Hospital of Hainan Medical University
city: Hangzhou
country: China
facility: Hangzhou Red Cross Hospital
city: Hefei
country: China
facility: Anhui Chest Hospital
city: Hohhot
country: China
facility: Second People's Hospital of Hohhot
city: Jiamusi
country: China
facility: Jiamusi Infectious Disease Hospital
city: Jiamusi
country: China
facility: Jiamusi Tumor Hospital
city: Jilin
country: China
facility: Jilin Tuberculosis Hospital
city: Linyi
country: China
facility: People's Hospital of Linyi
city: Nanjing
country: China
facility: Second Hospital of Nanjing
city: Nanning
country: China
facility: Fourth People's Hospital of Nanning
city: Nanning
country: China
facility: Guangxi Chest Hospital
city: Shandong
country: China
facility: Shandong public health clinical center
city: Shanghai
country: China
facility: National Medical Center for Infectious Disease
city: Shaoxing
country: China
facility: Affiliated Hospital of Shaoxing University
city: Shenyang
country: China
facility: Shenyang Chest Hospital
city: Shijiazhuang
country: China
facility: Shijiazhuang Fifth Hospital
city: Tianjin
country: China
facility: Tianjin Haihe Hospital
city: Weifang
country: China
facility: Second People's Hospital of Weifang
city: Wuhan
country: China
facility: Wuhan Institute For Tuberculosis Control
city: Xi'an
country: China
facility: Xi'an Chest Hospital
city: Xiamen
country: China
facility: First Affiliated Hospital of Xiamen Medical University
city: Xinxiang
country: China
facility: The First Affiliated Hospital of Xinxiang Medical University
city: Zhengzhou
country: China
facility: Henan Provincial Chest Hospital
city: Zunyi
country: China
facility: Affiliated Hospital of Zunyi Medical University
city: Ürümqi
country: China
facility: The 8th Affiliated Hospital of Xinjiang Medical University
Study officials:
References: