TCM as an Adjuvant Treatment in Mycobacterium Abscessus Pulmonary Disease

Official title

A Study to Assess the Traditional Chinese Medicine as Adjunctive Therapy to Improve Cure Rates During the Continuation Phase in Mycobacterium Abscessus Pulmonary Disease

Overview

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.

Detailed 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.

Interventions

• Drug Chinese herbs-I
  This is an empirical traditional Chinese medicine compound used in the treatment of Mycobacterium abscessus pulmonary disease for a long time
• Drug Chinese herbs-I placebo
  Chinese herbs-I placebo
• Drug Chinese herbs-II
  This is an empirical traditional Chinese medicine compound used in the treatment of Mycobacterium abscessus pulmonary disease during the continuation phase for a long time
• Drug Chinese herbs-II placebo
  Chinese herbs-II placebo

Primary outcome measures

• Clinical cure rate [Time frame: At the end of 52 weeks of treatment]
• Relapse or reinfection rates [Time frame: At the end of 52 weeks of treatment]

Secondary outcome measures (9)

• Time to sputum culture conversion [Time frame: From baseline to 52 weeks post-treatment completion]
• Absorption rate of lung lesions [Time frame: Baseline, 26 weeks and 52 weeks]
• Rate of closure of lung cavities [Time frame: Baseline, 26 weeks and 52 weeks]
• Pulmonary function tests [Time frame: Baseline, 26 weeks and 52 weeks]
• 6 minute walking test [Time frame: Baseline, 12 weeks, 26 weeks, 40 weeks and 52 weeks]
• 36 - item Short Form (SF - 36) [Time frame: Baseline, 12 weeks, 26 weeks, 40 weeks and 52 weeks]
• Quality of Life Questionnaire for Bronchiectasis (QoL-B) [Time frame: Baseline, 12 weeks, 26 weeks, 40 weeks and 52 weeks]
• Saint George's respiratory questionnaire (SGRQ) [Time frame: Baseline, 12 weeks, 26 weeks, 40 weeks and 52 weeks]
• Hospital Anxiety and Depression Scale (HADS) [Time frame: Baseline, 12 weeks, 26 weeks, 40 weeks and 52 weeks]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Triple blind

Primary purpose

Treatment

Study locations

China · 8 centers

• Beijing Chest Hospital Affiliated to Capital Medical University — Beijing
• China-Japan Friendship Hospital — Beijing
• Guangzhou Municipal Hospital of Chest Medicine — Guangdong
• Anhui Provincial Chest Hospital — Hefei
• Jiangxi Chest Hospital — Nanchang
• Fudan University Affiliated Huashan Hospital — Shanghai
• Longhua Hospital Affiliated Shanghai University of TCM — Shanghai
• Shanghai Pulmonary Hospital — Shanghai

Identifiers

NCT: NCT07295938 · 2024LCSY166

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗