Welte Tobias, Miravitlles Marc, Hernandez Paul, Eriksson Göran, Peterson Stefan, Polanowski Tomasz, Kessler Romain
Department of Respiratory Medicine, Hannover Medical School, Hannover, Germany.
Am J Respir Crit Care Med. 2009 Oct 15;180(8):741-50. doi: 10.1164/rccm.200904-0492OC. Epub 2009 Jul 30.
Budesonide/formoterol and tiotropium are commonly used maintenance treatments for patients with chronic obstructive pulmonary disease. Combining these medications may provide additional benefits.
To assess the efficacy and tolerability of budesonide/formoterol added to tiotropium in patients eligible for inhaled corticosteroid/long-acting beta(2)-agonist combination therapy.
In this 12-week, randomized, double-blind, parallel-group, multicenter study, after a 2-week run-in, 660 subjects (75% male; mean age, 62 yr; FEV(1), 1.1 L; 38% predicted normal), 40 years of age or older, received tiotropium (18 microg once daily) plus either budesonide/formoterol (320/9 microg) (n = 329) or placebo (n = 331) twice daily.
Clinic predose (primary outcome) and postdose FEV(1), predose and postdose forced vital capacity and inspiratory capacity, and health status were measured. Other outcomes included daily measurements taken at home (pre- and postdose morning FEV(1) and peak expiratory flow, morning symptoms and activities, and morning reliever use), severe exacerbations, and tolerability. Over the treatment period, budesonide/formoterol plus tiotropium significantly increased predose FEV(1) by 6% (65 ml) and postdose by 11% (123 and 131 ml at 5 and 60 min postdose, respectively) versus tiotropium alone (both P < 0.001). Other outcomes all significantly improved with budesonide/formoterol plus tiotropium versus tiotropium alone. The number of severe exacerbations decreased by 62% (rate ratio, 0.38; 95% confidence interval, 0.25-0.57; P < 0.001). Both treatments were well tolerated.
In patients with chronic obstructive pulmonary disease, budesonide/formoterol added to tiotropium versus tiotropium alone provides rapid and sustained improvements in lung function, health status, morning symptoms and activities, and reduces severe exacerbations. Clinical trial registered with www.clinicaltrials.gov (NCT00496470).
布地奈德/福莫特罗和噻托溴铵是慢性阻塞性肺疾病患者常用的维持治疗药物。联合使用这些药物可能会带来额外益处。
评估在适合吸入性糖皮质激素/长效β₂受体激动剂联合治疗的患者中，在噻托溴铵基础上加用布地奈德/福莫特罗的疗效和耐受性。
在这项为期12周的随机、双盲、平行组、多中心研究中，经过2周的导入期后，660名年龄40岁及以上的受试者（75%为男性；平均年龄62岁；第1秒用力呼气容积[FEV₁]为1.1L；占预计正常值的38%）接受噻托溴铵（每日1次，18μgμgμg�）加布地奈德/福莫特罗（320/9�）（n = 329）或安慰剂（n = 331），每日2次。
测量了临床给药前（主要结局）和给药后的FEV₁、给药前和给药后的用力肺活量及吸气量，以及健康状况。其他结局包括在家中进行的每日测量（给药前和给药后早晨的FEV₁和呼气峰值流速、早晨症状和活动情况以及早晨缓解药物使用情况）、严重加重发作情况和耐受性。在整个治疗期间，与单独使用噻托溴铵相比，布地奈德/福莫特罗加噻托溴铵使给药前FEV₁显著增加6%（65毫升），给药后5分钟和60分钟分别显著增加11%（123毫升和131毫升）（均P < 0.001）。与单独使用噻托溴铵相比，布地奈德/福莫特罗加噻托溴铵在其他结局方面也均有显著改善。严重加重发作次数减少了62%（率比，0.38；95%置信区间，0.25 - 0.57；P < 0.001）。两种治疗的耐受性均良好。
在慢性阻塞性肺疾病患者中，与单独使用噻托溴铵相比，在噻托溴铵基础上加用布地奈德/福莫特罗可使肺功能、健康状况、早晨症状和活动得到快速且持续的改善，并减少严重加重发作次数。该临床试验已在www.clinicaltrials.gov注册（NCT00496470）。
