Clinical trial NCT05494957: Clinical Study of New Intensive Treatment Regimen for Severe Nontuberculous Mycobacterial Pulmonary Disease
Official title: Clinical Study of New Intensive Treatment Regimen for Severe Nontuberculous Mycobacterial Pulmonary Disease
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE4
Conditions: Nontuberculous Mycobacterial Lung Disease
Keywords: Nontuberculous Mycobacterial Lung Disease
bedaquiline
Clofazimine
Lead sponsor: Shanghai Pulmonary Hospital, Shanghai, China
Sponsor class: OTHER
Collaborators: name: Shanghai Public Health Clinical Center
name: No.85 Hospital, Changning, Shanghai, China
name: Anhui Chest Hospital
name: Shanghai Pudong New Area Pulmonary Hospital, China
name: Huashan Hospital
name: Zhengzhou Sixth People's Hospital, China
First posted: 2022-08-10
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Treatment regimens containing bedaquiline, linezolid, clofazimine, and other drugs
Primary purpose: TREATMENT

Brief summary: Investigators have selected a number of new drugs, including bedaquiline, to form a regimen to conduct clinical studies for the treatment of severe NTM lung disease.

Detailed description: Currently, the annual prevalence of nontuberculous mycobacterial lung disease is increasing year by year. the clinical presentation of NTM is similar to that of tuberculosis, but most NTM is severely resistant to antibiotics, making it difficult to treat, and it responds poorly to classical antituberculous mycobacterial drugs. the overall response rate for the treatment of NTM lung disease is approximately 50% according to current domestic and international treatment guidelines. In severe NTM lung disease, after more than one anti-mycobacterial treatment, the resistance rate is even higher, the disease is more severe, and treatment is even more difficult. Current clinical treatment regimens are mainly long courses and combinations of drugs, however, the results are often unsatisfactory with an overall cure rate of only 30%. Therefore, we need to continue to explore new effective drugs for NTM lung disease and explore new and more effective drug regimens.

Several drugs have shown promising effects in basic research and clinical applications for NTM. For example, clofazimine has shown good efficacy in the treatment of nontuberculous mycobacterial lung disease. In addition, some new antibiotics or anti-tuberculosis drugs have attracted attention for showing good anti-NTM effects in in vitro experiments, such as tigecycline, linezolid, and bedaquiline. Based on the clinical experience of the investigators and related basic research, we conducted a clinical study of new regimens for intensive treatment of severe non-tuberculous mycobacterial lung disease.

Eligibility criteria: Inclusion Criteria:

1. Patients with non-tuberculous mycobacterial lung disease who meet the diagnostic criteria of the American Thoracic Society and British Thoracic Society guidelines or the Chinese Expert Consensus on the Diagnosis and Treatment of Non-tuberculous Mycobacteriosis (2020) and whose strain is identified as Mycobacterium intracellulare/abscessus
2. Proposed anti-NTM therapy based on current disease.
3. Patients aged 18 to 65 years.
4. able to understand and have signed an informed consent form.
5. culture drug sensitivity results showing resistance to clarithromycin; or previous anti-NTM therapy has been ineffective.
6. Patients with severe NTM lung disease, with chest CT showing greater than 50% of the extent of infection lesions in both lungs; or with short-term progressive worsening of the disease.

Exclusion Criteria:

1. History of allergy to any drug in the protocol
2. Combined hepatic, renal, metabolic, autoimmune diseases, endocrine, hematological, neurological diseases, psychiatric disorders, malignancies, long-term immunosuppressive drugs or HIV/AIDS patients
3. QTc interval \>470 ms in women and \>450 ms in men
4. Severe pulmonary hypoplasia (FEV \<30%)
5. Those with co-infection with other Mycobacterium species
6. Pregnant or breastfeeding females.
7. Those who are also participating in other clinical studies.

Primary outcomes:
measure: Treatment Outcome
timeFrame: Treatment period, approximately 12 months.
Secondary outcomes:
measure: Improvement rate of imaging
timeFrame: Treatment period, approximately 12 months.
Other outcomes:
measure: Improvement in lung function
timeFrame: Treatment period, approximately 12 months.
measure: Adverse Events
timeFrame: Treatment period, approximately 12 months.
measure: Mycobacterial culture negative conversion rate
timeFrame: Treatment period, approximately 12 months.
Locations:
city: Shanghai
country: China
facility: Shanghai Pulmonary Hospital
Study officials:
References: