Comparison of Two- Versus Three-antibiotic Therapy for Pulmonary Mycobacterium Avium Complex Disease
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 474
- 试验地点
- 26
- 主要终点
- Therapy completion
研究概览
简要总结
NTM therapy consists of a multi-drug macrolide based regimen for 18-24 months. Treated patients frequently experience debilitating side effects, and many patients delay the start of antibiotic treatment due to these risks. Common side effects include nausea, diarrhea, and fatigue, and rare but serious toxicities include ocular toxicity, hearing loss, and hematologic toxicity. To date, most of the evidence underlying the current treatment recommendations has come from observational studies in which either a macrolide has been combined with rifampin and ethambutol, or in some cases combined with ethambutol alone. The proposed study will answer whether a third drug is necessary or whether taking two drugs can increase tolerability without a substantial loss of efficacy.
详细描述
Mycobacterium avium complex (MAC) are a subset of nontuberculous mycobacteria (NTM), environmental bacteria that can cause chronic, debilitating pulmonary disease, primarily affecting those over age 60. The goals of treatment are to improve symptoms, stop disease progression, and clear the infection. We propose to address a longstanding controversy in the therapy of pulmonary MAC disease, whether patients must take three antibiotics concomitantly, or if two are sufficient. The study is a multicenter randomized pragmatic clinical trial to compare azithromycin + ethambutol (2-drug therapy) vs. azithromycin + ethambutol + rifampin (3-drug therapy) for non-cavitary pulmonary MAC disease. All clinical outcomes will be considered standard of care and abstracted from clinical records. Therapy changes and adverse events will be recorded at routine visits. Health-related quality of life (HRQoL) and self-reported toxicity will be captured centrally in a web-based database, and CT scans will be read centrally. Co-primary outcomes are culture conversion and tolerability of treatment. The primary analysis for culture conversion will be conducted as a per-protocol non-inferiority analysis, and the primary analysis for tolerability will be conducted as an intention-to-treat superiority analysis.
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
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Culture positive pulmonary MAC meeting ATS/IDSA disease criteria
- •Age over 18 years
- •Ability to provide informed consent
排除标准
- •Fibrocavitary disease
- •Planned surgery for MAC disease
- •Patients who have cumulatively taken 6 weeks or more of multi-drug antimicrobial treatment for MAC
- •Patients who are currently taking or have taken multi-drug antimicrobial treatment for NTM within the prior 30 days
- •Diagnosis of Cystic fibrosis
- •Diagnosis of HIV
- •History of solid organ or hematologic transplant
- •Significant drug-drug interaction not clinically manageable in the opinion of the investigator
- •Contraindication to any component of the study treatment regimen
研究组 & 干预措施
2-drug regimen
This arm is a 3 time per week (TIW) treatment regimen that includes azithromycin 500 mg po + ethambutol 25 mg/kg Treatment changes are at the discretion of the treating physician and patient. Where possible, changes in dosing or frequency that allow the patient to continue taking the assigned drugs during the 12 months study period are preferred.
干预措施: Azithromycin (Drug)
2-drug regimen
This arm is a 3 time per week (TIW) treatment regimen that includes azithromycin 500 mg po + ethambutol 25 mg/kg Treatment changes are at the discretion of the treating physician and patient. Where possible, changes in dosing or frequency that allow the patient to continue taking the assigned drugs during the 12 months study period are preferred.
干预措施: Ethambutol (Drug)
3-drug regimen
This arm is a 3 time per week (TIW) treatment regimen that includes azithromycin 500 mg po + ethambutol 25 mg/kg + rifampin 600 mg Treatment changes are at the discretion of the treating physician and patient. Where possible, changes in dosing or frequency that allow the patient to continue taking the assigned drugs during the 12 months study period are preferred.
干预措施: Azithromycin (Drug)
3-drug regimen
This arm is a 3 time per week (TIW) treatment regimen that includes azithromycin 500 mg po + ethambutol 25 mg/kg + rifampin 600 mg Treatment changes are at the discretion of the treating physician and patient. Where possible, changes in dosing or frequency that allow the patient to continue taking the assigned drugs during the 12 months study period are preferred.
干预措施: Ethambutol (Drug)
3-drug regimen
This arm is a 3 time per week (TIW) treatment regimen that includes azithromycin 500 mg po + ethambutol 25 mg/kg + rifampin 600 mg Treatment changes are at the discretion of the treating physician and patient. Where possible, changes in dosing or frequency that allow the patient to continue taking the assigned drugs during the 12 months study period are preferred.
干预措施: Rifampin (Drug)
结局指标
主要结局
Therapy completion
时间窗: 12 months post randomization
The proportion of patients who complete 12 months of therapy on their assigned regimen with "satisfactory adherence". "Satisfactory adherence" is defined as taking 80% of their prescribed doses/not missing more than 75 days of treatment.
Acid-fast bacilli (AFB) culture negativity
时间窗: 12 months post randomization
Two consecutive negative AFB cultures by 12 months post randomization without reversion to positive
次要结局
- Gastrointestinal AE proportion(up to 12 months)
- Fatigue AE proportion(Cumulative to 12 months)
- NTM Symptoms Score(12 months post randomization)
- PROMIS Fatigue 7a short form score(12 months post randomization)
- QOL-B Respiratory Symptoms Score(12 months post randomization)
- Liver AE proportion(up to 12 months)
- Macrolide resistance(12 months post randomization)
研究者
Kevin Winthrop
Professor
Oregon Health and Science University