Eosinophil-guided Reduction of Inhaled Corticosteroids
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 444
- 试验地点
- 9
- 主要终点
- Exacerbations, hospital and death
研究概览
简要总结
Clinical trial on eosinophil-guided time-updated person-specific reduction of inhaled corticosteroid (ICS) therapy and prophylactic azithromycin therapy in patients with severe or very severe chronic obstructive pulmonary disease (COPD) receiving long-acting b-agonist (LABA) / long-acting muscarinic receptor antagonists (LAMA) / ICS treatment.
详细描述
Inhaled corticosteroid (ICS) treatment is recommended by Global Initiative for Obstructive Lung Disease (GOLD) for patients with frequent and/or servere exacerbations and blood eosinophils > 0.3 x 10^9 cells/L and in those with ≥ 0,1 x 109 cells blood-eosinophils and recurrent exacerbations while on bronchodilators. ICS treatment, however, is associated with side effects such as diabetes, osteoporosis and pneumonia which is costly for both patients and society. By studying the effects of a personalized, eoseosinophil-guided approach to direct ICS in COPD patients with frequent AECOPDs through a randomized clinical trial this study will examine the possibilities of reducing ICS overtreatment and thus ICS-related adverse events.
Long term ICS treatment is known for affecting the bacterial load in stable COPD patients. Azithromycin exerts multiple effects on the structure and composition of the lower airway microbiota and has anti-inflammatory effects. This study will, moreover, investigate whether an oral low-dose prophylactic treatment with Azithromycin 250 mg three times weekly can reduce the number of moderate-severe AECOPD and improves time alive and out of hospital.
This study is a randomized, double-blinded, multicentre, four-arm intervention clinical trial and is conducted based on the principles of good clinical practise (GCP).
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 40 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •COPD (verified by a specialist in respiratory medicine + spirometry)
- •GOLD class E anytime within the last 2 years (corresponding to 2 ≥ AECOPD and/or ≥1 AECOPD leading to hospitalization during a 12 months period within the last 2 years) and/or FEV1<30%.
- •Treatment for last 4 weeks including LAMA, LABA and ICS
- •Informed consent
排除标准
- •Known asthma.
- •Male < 40 years.
- •Female <40 years, if non-menopausal (had menstruation within the last 12 months) conditioned by a negative urine HCG test
- •Severe mental illness which considerably complicates co-operation.
- •Language problems that considerably complicate co-operation.
- •Current treatment with systemic corticosteroids corresponding to > 5 mg prednisolone per day.
- •Systemic antibiotic treatment (if to participate in microbiota sub-study) or systemic corticosteroid treatment within 14 days (also prophylactic Azithromycin).
- •Contra-indication to treat with Azithromycin (as listed by the producer).
- •Non-bacterial exacerbation per investigator judgement in the last 3 months.
研究组 & 干预措施
Eosinophil_"Active"/Azithro_"Control":
a. Azithromycin: placebo b. ICS: All patients will receive LABA/LAMA medication. The ICS medication will be switched on/off according to the most recent blood eosinophil count (at inclusion + every 3 months): i. If blood eosinophil ≥ 300 cells/μL, ICS in usual dose next 3 months. Blood eosinophils are measured every 3 months.
ii. If blood eosinophil <300 cells/μL, ICS is discontinued.
干预措施: ICS (Drug)
Eosinophil_"Control"/Azithro_"Active" group
Azithromycin: 250 mg azithromycin three times weekly. b. ICS: The patients are given the usual LAMA/LABA/ICS product in the usual dose, where the medical treatment for severe COPD is unchanged throughout the entire project period
干预措施: Azithromycin (Drug)
Eosinophil_"Active"/Azithro_"Active":
- Azithromycin: 250 mg azithromycin three times weekly.
- ICS: All patients will receive LABA/LAMA medication. The ICS medication will be switched on/off according to the most recent blood eosinophil count (at inclusion + every 3 months):
干预措施: Azithromycin (Drug)
Eosinophil_"Active"/Azithro_"Active":
- Azithromycin: 250 mg azithromycin three times weekly.
- ICS: All patients will receive LABA/LAMA medication. The ICS medication will be switched on/off according to the most recent blood eosinophil count (at inclusion + every 3 months):
干预措施: ICS (Drug)
Eosinophil_"Control"/Azithro_"Control"
- Azithromycin: patients are given placebo
- ICS: The patients are given the usual LAMA/LABA/ICS product in the usual dose.
结局指标
主要结局
Exacerbations, hospital and death
时间窗: 365 days
Number of hospitalization-requiring exacerbations within 12 months and/or death within 365 days
次要结局
- Change in FEV1(365 days)
- Days alive, out of hospital(365 days)
- Change in MRC dyspnoea score(365 days)
- Deaths, uncontrolled AECOPD(365 days)
- Cumulative ICS dose(365 days)
- Cumulative OCS dose(365 days)
- Change in blood eosinophils(365 days)
- Microbiota, abundance and diversity(365 days)
- Number of exacerbations(365 days)
- Change in HbA1c(365 days)
- Number of antibiotic requiring infections(365 days)
- Diabetes mellitus(365 days)
- Mortality(365 days)
- Microbiota, immunological profile(365 days)
- Change in CAT score(365 days)
- Number of non-invasive ventilation (NIV) or intensive care admissions or death(365 days)