Vermeersch Kristina, Gabrovska Maria, Deslypere Griet, Demedts Ingel K, Slabbynck Hans, Aumann Joseph, Ninane Vincent, Verleden Geert M, Troosters Thierry, Bogaerts Kris, Brusselle Guy G, Janssens Wim
KU Leuven, Laboratory of Respiratory Diseases, Department of Clinical and Experimental Medicine, Faculty of Medicine, Leuven, Belgium.
Department of Pneumology, Centre Hospitalier Universitaire Saint-Pierre, Brussels, Belgium.
Int J Chron Obstruct Pulmon Dis. 2016 Mar 31;11:687-96. doi: 10.2147/COPD.S95501. eCollection 2016.
Long-term use of macrolide antibiotics is effective to prevent exacerbations in chronic obstructive pulmonary disease (COPD). As risks and side effects of long-term intervention outweigh the benefits in the general COPD population, the optimal dose, duration of treatment, and target population are yet to be defined. Hospitalization for an acute exacerbation (AE) of COPD may offer a targeted risk group and an obvious risk period for studying macrolide interventions.
METHODS/DESIGN: Patients with COPD, hospitalized for an AE, who have a smoking history of ≥10 pack-years and had ≥1 exacerbation in the previous year will be enrolled in a multicenter, randomized, double-blind, placebo-controlled trial (NCT02135354). On top of a standardized treatment of systemic corticosteroids and antibiotics, subjects will be randomized to receive either azithromycin or placebo during 3 months, at an uploading dose of 500 mg once a day for 3 days, followed by a maintenance dose of 250 mg once every 2 days. The primary endpoint is the time-to-treatment failure during the treatment phase (ie, from the moment of randomization until the end of intervention). Treatment failure is a novel composite endpoint defined as either death, the admission to intensive care or the requirement of additional systemic steroids or new antibiotics for respiratory reasons, or the diagnosis of a new AE after discharge.
We investigate whether azithromycin initiated at the onset of a severe exacerbation, with a limited duration and at a low dose, might be effective and safe in the highest risk period during and immediately after the acute event. If proven effective and safe, this targeted approach may improve the treatment of severe AEs and redirect the preventive use of azithromycin in COPD to a temporary intervention in the subgroup with the highest unmet needs.
长期使用大环内酯类抗生素可有效预防慢性阻塞性肺疾病（COPD）急性加重。由于在一般COPD患者群体中，长期干预的风险和副作用超过了益处，因此最佳剂量、治疗持续时间和目标人群仍有待确定。COPD急性加重（AE）住院患者可能为研究大环内酯类药物干预提供一个有针对性的风险群体和一个明显的风险期。
方法/设计：因AE住院、吸烟史≥10包年且前一年有≥1次加重的COPD患者将被纳入一项多中心、随机、双盲、安慰剂对照试验（NCT02135354）。在全身用糖皮质激素和抗生素的标准化治疗基础上，受试者将被随机分组，在3个月内接受阿奇霉素或安慰剂治疗，起始剂量为500mg每日1次，共3天，随后维持剂量为250mg每2日1次。主要终点是治疗阶段的治疗失败时间（即从随机分组时刻至干预结束）。治疗失败是一个新的复合终点，定义为死亡、入住重症监护病房、因呼吸原因需要额外的全身用糖皮质激素或新的抗生素，或出院后诊断为新的AE。
我们研究在严重加重发作开始时、有限疗程且低剂量使用阿奇霉素在急性事件期间及之后的最高风险期是否可能有效且安全。如果被证明有效且安全，这种有针对性的方法可能会改善严重AE的治疗，并将COPD中阿奇霉素的预防性使用重新导向对需求未得到满足程度最高的亚组进行临时干预。
