TCM as an Adjuvant Treatment in Mycobacterium Abscessus Pulmonary Disease

Shanghai University of Traditional Chinese Medicine

Status and phase: Enrolling; Phase 2

Conditions: Mycobacterium Abscessus Pulmonary Disease

Treatments: Drug: Chinese herbs-I placebo; Drug: Chinese herbs-I; Drug: Chinese herbs-II; Drug: Chinese herbs-II placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT07295938

2024LCSY166

Details and patient eligibility

About

Chinese herbs can facilitate sputum culture conversion, promote lesion absorption, and enhance clinical symptoms and quality of life for patients with Mycobacterium abscessus pulmonary disease (MAB-PD). The investigators aimed to evaluate the efficacy of Chinese herbs as adjunct therapy to improve cure rates or reduce recurrence rates during the continuation phase of MAB-PD treatment.

Full description

Mycobacterium abscessus pulmonary disease (MAB-PD) is a significant form of non-tuberculous mycobacterial lung infection that clinically presents with symptoms such as cough, sputum production, hemoptysis, low-grade fever, and chest tightness. Current guidelines recommend treatment regimens that are divided into initial and continuation phases. The initial phase involves combination therapy with at least three antibiotics, which can be administered intravenously or orally. In contrast, the continuation phase requires the use of oral or inhaled antibiotics. Guidelines suggest continuing treatment for 12 months after sputum culture negativity, although standard protocols indicate only a 35% cure rate with up to a 40% post-treatment relapse rate. Research has shown that traditional Chinese herbal formulas have broad immunomodulatory effects, which promote sputum culture conversion, lesion absorption, and improvement in clinical symptoms and quality of life for patients with MAB-PD. This study will enroll patients with MAB-PD who have completed initial treatment and will be divided into two independent randomized controlled trials (RCTs) based on sputum M.abscessus culture results. RCT-1 will include patients with persistently positive bacterial cultures receiving Chinese herbal therapy supplemented with the guideline-recommended regimen, with primary endpoints being 52-week cure rates. RCT-2 will include patients with negative bacterial cultures receiving Chinese herbal therapy supplemented with the guideline-recommended regimen, with primary endpoints being 52-week rates of relapse or reinfection. Patients will receive complimentary Chinese herbal medicine. All participants will undergo sputum or bronchoalveolar lavage fluid bacteriological testing, chest imaging, pulmonary function tests, a 6-minute walk test, SF-36, QOL-B, SGRQ, and HADS scales. Additionally, exploratory studies will collect sputum, bronchoalveolar lavage fluid, blood, and stool samples to identify the comprehensive immune profile of MAB-PD and evaluate the intervention advantages of traditional Chinese medicine.

Enrollment: 352 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Patient diagnosed with Mycobacterium abscessus pulmonary disease;
• Patients have completed the initial phase of treatment as recommended by the guidelines;
• Patients who have given written informed consent
• One week prior to enrollment, organ function levels must meet the following criteria: a. Hemoglobin ≥60g/L; b. Neutrophil count ≥0.5×10^9/L; c. Platelet count ≥60×10^9/L; d. Serum total bilirubin ≤3 times the upper limit of normal; e. Aspartate aminotransferase ≤3 times the upper limit of normal; f. Alanine aminotransferase ≤3 times the upper limit of normal; g. Creatinine level below 2 times the upper limit of normal or creatinine clearance ≥60mL/min; h. Urea nitrogen ≤200mg/L; i. Urinary protein <++, with ≥500mg total protein in 24-hour urine if protein is present; j. Blood glucose: within normal range and/or stable blood glucose control in diabetic patients; k. Cardiac function: no history of myocardial infarction within 6 months; no unstable angina; no severe arrhythmia.

Exclusion criteria

• Patients with a drug allergy to the investigational medication;
• Patients infected with two or more non-tuberculous mycobacteria, or those with active pulmonary tuberculosis;
• Patients with a prior history of pulmonary parenchymal organ transplantation;
• Patients with severe conditions such as congenital or acquired immunodeficiency disorders, active malignant tumors (primary or metastatic), or any malignancies requiring chemotherapy or radiotherapy during screening or study;
• Patients undergoing dialysis;
• Patients with radiation pneumonitis requiring corticosteroid or immunoglobulin pulse therapy, or clinically proven active interstitial lung disease, uncontrolled massive pleural effusion, or pericardial effusion;
• Unstable systemic comorbidities (hypertensive crisis, unstable angina, congestive heart failure, myocardial infarction within the past 6 months, severe psychiatric disorders requiring medication, severe hepatic or renal dysfunction, neuropsychiatric conditions such as Alzheimer's disease);
• Patients with intestinal dysfunction or malabsorption syndrome;
• Pregnant or breastfeeding women;
• Patients receiving other investigational drugs within 4 weeks prior to first exposure to the study drug;
• Concurrent enrollment in another clinical trial, except for observational (non-interventional) studies or follow-up visits in interventional trials;
• Physical examinations or clinical tests that the investigator deems potentially interfering with results or increasing treatment-related complications.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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352 participants in 4 patient groups, including a placebo group

Treatment Group-I

Experimental group

Description:

104 participants with persistently positive bacterial cultures during the continuation phase received Chinese herbal therapy in addition to the guideline-recommended regimen, with the primary endpoint being the cure rates at 52 weeks.

Treatment:

Drug: Chinese herbs-I

Control Group-I

Placebo Comparator group

Description:

104 participants with persistently positive bacterial cultures during the continuation phase received a placebo comprising a 1/20 dose of Chinese herbs in addition to the guideline-recommended regimen, with the primary endpoint being the cure rates at 52 weeks.

Treatment:

Drug: Chinese herbs-I placebo

Treatment Group-II

Experimental group

Description:

72 participants with negative bacterial cultures during the continuation phase received Chinese herbal therapy in addition to the guideline-recommended regimen, with the primary endpoint being the relapse or reinfection rates at 52 weeks.

Treatment:

Drug: Chinese herbs-II

Control Group-II

Placebo Comparator group

Description:

72 participants with negative bacterial cultures during the continuation phase received a placebo comprising a 1/20 dose of Chinese herbs in addition to the guideline-recommended regimen, with the primary endpoint being the relapse or reinfection rates at 52 weeks.

Treatment:

Drug: Chinese herbs-II placebo