A Study to Assess the Traditional Chinese Medicine as Adjunctive Therapy to Improve Cure Rates During the Continuation Phase in Mycobacterium Abscessus Pulmonary Disease
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 352
- 试验地点
- 8
- 主要终点
- Clinical cure rate
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
盲法说明
This is a Double-blind Trial
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
Treatment Group-I
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.
干预措施: Chinese herbs-I (Drug)
Control Group-I
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.
干预措施: Chinese herbs-I placebo (Drug)
Treatment Group-II
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.
干预措施: Chinese herbs-II (Drug)
Control Group-II
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.
干预措施: Chinese herbs-II placebo (Drug)
结局指标
主要结局
Clinical cure rate
时间窗: At the end of 52 weeks of treatment
Measured the change from the Baseline to the end of treatment. The sputum MAB culture was negative on three consecutive occasions, with at least a one-month interval between each, and there were no subsequent positive results.
Relapse or reinfection rates
时间窗: At the end of 52 weeks of treatment
Bacterial relapse is defined as the occurrence of at least two cultures and/or molecular biology tests identifying the same pathogenic M. abscessus strain as the initial infection after completing anti-M. abscessus treatment. When necessary, genotyping techniques may be employed to differentiate between relapse and reinfection. Reinfection refers to the emergence of different pathogenic strains or species in at least two positive cultures following the initiation of treatment.
次要结局
- Time to sputum culture conversion(From baseline to 52 weeks post-treatment completion)
- Absorption rate of lung lesions(Baseline, 26 weeks and 52 weeks)
- Rate of closure of lung cavities(Baseline, 26 weeks and 52 weeks)
- Quality of Life Questionnaire for Bronchiectasis (QoL-B)(Baseline, 12 weeks, 26 weeks, 40 weeks and 52 weeks)
- Pulmonary function tests(Baseline, 26 weeks and 52 weeks)
- 6 minute walking test(Baseline, 12 weeks, 26 weeks, 40 weeks and 52 weeks)
- 36 - item Short Form (SF - 36)(Baseline, 12 weeks, 26 weeks, 40 weeks and 52 weeks)
- Saint George's respiratory questionnaire (SGRQ)(Baseline, 12 weeks, 26 weeks, 40 weeks and 52 weeks)
- Hospital Anxiety and Depression Scale (HADS)(Baseline, 12 weeks, 26 weeks, 40 weeks and 52 weeks)
研究者
Zhenhui Lu
chief physician
Shanghai University of Traditional Chinese Medicine