Rønn Christian, Bonnesen Barbara, Alispahic Imane Achir, Tønnesen Louise Lindhardt, Kjærgaard Jakob Lyngby, Moberg Mia, Ulrik Charlotte Suppli, Harboe Zitta Barrella, Browatzki Andrea, Jensen Torben Tranborg, Meyer Christian N, Bodtger Uffe, Bendstrup Elisabeth, Johansson Sofie Lock, Kaiser Diana Utech, Hyldgaard Charlotte, Vestbo Jørgen, Sivapalan Pradeesh, Jensen Jens-Ulrik Stæhr
Department of Internal Medicine, Copenhagen Respiratory Research, Copenhagen University Hospital - Gentofte, Hellerup, Denmark.
Department of Respiratory Medicine, Copenhagen University Hospital - Hvidovre, Hvidovre, Denmark.
Trials. 2025 Sep 2;26(1):335. doi: 10.1186/s13063-025-09032-0.
Inhaled corticosteroid (ICS) is frequently used for COPD. Based on the considerable adverse effects and the knowledge that many such patients do not gain benefit from this treatment, it remains unresolved whether ICS treatment can be managed with lower doses, or via an ICS-sparing strategy with periods with and without this medicine. The blood eosinophil count is a useful biomarker for steroid-responsive airway inflammation, and we want to investigate whether an individualized and eosinophil-guided approach on ICS treatment reduces ICS over-treatment and side effects. High-dose (500 mg thrice weekly or 250 mg daily) long-term azithromycin has been shown to reduce acute exacerbations of COPD in selected patients. Frequent gastro-intestinal adverse effects remain a challenge, but many patients tolerate lower doses; however, the effect of the treatment at lower doses is unknown, although many physicians prefer such doses. We want to investigate whether oral low-dose prophylactic azithromycin 250 mg three times weekly reduces acute exacerbations of COPD and improves time alive and out of hospital.
This is an ongoing, actively recruiting randomized, double-blinded, multicenter, four-arm factorial intervention clinical trial aiming to recruit 444 patients with specialist verified COPD GOLD risk class E and/or FEV1 < 30% who are currently on ICS. The patients are followed for one year and are randomized 1:1:1:1 to one of the four treatment arms: (1) eosinophil-guided ICS-sparing treatment and low-dose azithromycin, (2) eosinophil-guided ICS treatment and placebo, (3) continued ICS treatment and low-dose azithromycin, or (4) continued ICS treatment and placebo. If blood-eosinophils (measured every 3 months) are < 0.3 × 10 cells/L, ICS treatment will be paused in the arms with eosinophil-guided ICS-sparing treatment. Azithromycin/placebo is double-blinded and administered three times weekly. The primary endpoint is the number of hospitalization-requiring COPD exacerbations and/or death within 365 days.
Severe ICS-adverse effects like bacterial infections should be reduced. The ICS-sparing intervention, we test, may provide a useful tool to do this safely. Azithromycin low-dose prophylaxis is practiced by many physicians. This trial will provide evidence of whether this is effective.
ClinTrials.gov. NCT04481555. Registered on 14 AUG 2020, https://clinicaltrials.gov/study/NCT04481555 .
吸入性糖皮质激素（ICS）常用于慢性阻塞性肺疾病（COPD）。鉴于其存在相当多的不良反应，且许多此类患者并未从该治疗中获益，目前仍未解决的问题是，ICS治疗能否采用更低剂量进行管理，或者通过一种有药期和无药期交替的ICS节约策略来进行管理。血液嗜酸性粒细胞计数是类固醇反应性气道炎症的有用生物标志物，我们想研究个体化的、以嗜酸性粒细胞为导向的ICS治疗方法是否能减少ICS的过度治疗及其副作用。高剂量（每周三次500毫克或每日250毫克）长期使用阿奇霉素已被证明可减少特定患者的COPD急性加重。频繁的胃肠道不良反应仍是一个挑战，但许多患者能耐受较低剂量；然而，较低剂量治疗的效果尚不清楚，尽管许多医生倾向于使用此类剂量。我们想研究口服低剂量预防性阿奇霉素（每周三次250毫克）是否能减少COPD急性加重，并改善存活和非住院时间。
这是一项正在进行的、正在积极招募患者的随机、双盲、多中心、四臂析因干预临床试验，旨在招募444名经专科医生确诊为COPD GOLD风险等级E和/或FEV1<30%且目前正在使用ICS的患者。对患者进行一年的随访，并将他们以1:1:1:1的比例随机分配到四个治疗组之一：（1）以嗜酸性粒细胞为导向的ICS节约治疗和低剂量阿奇霉素，（2）以嗜酸性粒细胞为导向的ICS治疗和安慰剂，（3）继续使用ICS治疗和低剂量阿奇霉素，或（4）继续使用ICS治疗和安慰剂。如果血液嗜酸性粒细胞（每3个月测量一次）<0.3×10⁹/L，则在以嗜酸性粒细胞为导向的ICS节约治疗组中暂停ICS治疗。阿奇霉素/安慰剂采用双盲法，每周给药三次。主要终点是365天内需要住院治疗的COPD急性加重次数和/或死亡情况。
应减少如细菌感染等严重的ICS不良反应。我们所测试的ICS节约干预措施可能为安全地做到这一点提供一个有用的工具。许多医生都采用低剂量阿奇霉素预防措施。该试验将提供这是否有效的证据。
美国国立医学图书馆临床试验注册库。NCT04481555。于2020年8月14日注册，https://clinicaltrials.gov/study/NCT04481555 。
