Bleecker E R, Tinkelman D G, Ramsdell J, Ekholm B P, Klinger N M, Colice G L, Slade H B
Department of Medicine, University of Maryland, Baltimore, USA.
Chest. 1998 Feb;113(2):283-9. doi: 10.1378/chest.113.2.283.
To compare the bronchodilator effectiveness of albuterol reformulated in the chlorofluorocarbon-free propellant hydrofluoroalkane (HFA)134a (Proventil HFA) to that of Ventolin and HFA placebo over 12 weeks of regular dosing.
Randomized, double-blind, double-dummy, parallel group, placebo-controlled, multi-center trial of asthmatics requiring inhaled beta-adrenergic bronchodilators for symptom control.
Treatment qid with Proventil HFA, Ventolin, or HFA-134a placebo for 12 weeks.
At weeks 0, 4, 8, and 12, spirometry was performed predose and serially over 6 h after dosing with study drug. Bronchodilator efficacy variables, based on FEV1 response to study drug, were proportion of responders, time to onset of effect, peak percent change, time to peak effect, duration of effect, and area under the curve (AUC).
Demographic and baseline characteristics were similar for patients randomized to Proventil HFA (193), Ventolin (186), and HFA-134a placebo (186). No significant differences were found between the Proventil HFA and Ventolin treatment groups for any FEV1 efficacy variable, either predose or during 6 h of serial spirometry, at weeks 0, 4, 8, and 12. For all efficacy variables, except time to onset of effect, the Proventil HFA and Ventolin results were significantly greater than placebo. Time to onset of effect for the HFA-134a placebo group is misleading; only 13 patients (7%) were found to be responders in the intent-to-treat database. These efficacy results were found to be consistent across subgroup analyses of inhaled and nasal corticosteroid use, age (18 to 35 and 36 to 66 years), sex, race, weight (<60, 60 to 100, and >100 kg), and baseline FEV1 (< or =55% and >55% predicted). The peak FEV1 effect, duration of FEV1 effect, and AUC for FEV1 were all significantly smaller at weeks 4, 8, and 12 than week 0 for both the Proventil HFA and Ventolin treatment groups.
Proventil HFA provided bronchodilation comparable to Ventolin and superior effects to HFA-134a placebo over 12 weeks of regular dosing. There was a diminution in bronchodilator response to both Proventil HFA and Ventolin after 4 weeks of use.
比较在12周常规给药期间，用无氯氟烃推进剂氢氟烷烃（HFA）134a重新配制的沙丁胺醇（普米克令舒HFA）与万托林及HFA安慰剂的支气管扩张效果。
针对需要吸入β-肾上腺素能支气管扩张剂来控制症状的哮喘患者进行的随机、双盲、双模拟、平行组、安慰剂对照、多中心试验。
用普米克令舒HFA、万托林或HFA-134a安慰剂每日四次治疗12周。
在第0、4、8和12周，在给药前及给药后6小时内连续进行肺功能测定。基于第一秒用力呼气量（FEV1）对研究药物的反应，支气管扩张疗效变量包括反应者比例、起效时间、峰值变化百分比、达峰时间、作用持续时间和曲线下面积（AUC）。
随机分配至普米克令舒HFA组（193例）、万托林组（186例）和HFA-134a安慰剂组（186例）的患者，其人口统计学和基线特征相似。在第0、4、8和12周，无论是给药前还是在连续6小时的肺功能测定期间，普米克令舒HFA组和万托林治疗组在任何FEV1疗效变量上均未发现显著差异。对于所有疗效变量，除起效时间外，普米克令舒HFA组和万托林组的结果均显著优于安慰剂。HFA-134a安慰剂组的起效时间具有误导性；在意向性治疗数据库中仅发现13例患者（7%）为反应者。在吸入和鼻用糖皮质激素使用情况、年龄（18至35岁和36至66岁）、性别、种族、体重（<60、60至100和>100 kg）以及基线FEV（<或=55%和>55%预测值）的亚组分析中，这些疗效结果是一致的。普米克令舒HFA组和万托林治疗组在第4、8和12周时，FEV1的峰值效应、FEV1效应持续时间和AUC均显著小于第0周。
在12周常规给药期间，普米克令舒HFA的支气管扩张效果与万托林相当，且优于HFA-134a安慰剂。使用4周后，普米克令舒HFA和万托林的支气管扩张反应均有所减弱。
