Amin Reshma, Stanojevic Sanja, Kane Mica, Webster Hailey, Ratjen Felix
Division of Respiratory Medicine, Hospital for Sick Children, Toronto, Canada; University of Toronto, Toronto, Canada; Child Health and Evaluative Sciences, Research Institute, Hospital for Sick Children, Toronto, Canada.
Division of Respiratory Medicine, Hospital for Sick Children, Toronto, Canada; University of Toronto, Toronto, Canada; Physiology and Experimental Medicine, Research Institute, Hospital for Sick Children, Toronto, Canada.
Respir Med. 2016 Mar;112:59-64. doi: 10.1016/j.rmed.2016.01.020. Epub 2016 Feb 2.
Outcome measures that can evaluate treatment efficacy are important to enhance development of new therapeutic agents for Cystic Fibrosis (CF). We investigated whether the lung clearance index (LCI) measured by multiple breath washout (MBW) can detect a treatment effect of hypertonic saline (HS) inhalation after single dosing within a 24 h period.
In this randomized controlled cross-over trial, CF patients received inhalation of HS and isotonic saline (IS). MBW and spirometry were performed at 5 time points over 24 h. LCI was measured using both a nitrogen washout technique (LCIN2) and sulfur hexafluoride as a tracer gas (LCISF6). The primary endpoint was the change in the LCIN2 between baseline and 24 h. Secondary endpoints included change in LCISF6 and spirometry outcomes.
Twenty-one patients were randomized. Sixteen completed all study visits and all time point measurements. Eighteen patients contributed to the intention to treat analysis. Significant changes were not detected for either LCI or the spirometry outcomes. However, the primary outcome parameter (change in LCI between the baseline visits and 24 h after inhalation) demonstrated a trend towards improved LCI, in the HS treatment arm compared with the IS treatment arm, -0.60 LCIN2 (SE 0.32), p = 0.08); similar trends were not observed for spirometric measures. The overall effect size of HS was smaller than in previous studies of longer duration.
These data suggest that LCI may potentially be used as an outcome measure in early phase trials with therapeutic agents that have a larger treatment effects than a single inhalation of HS.
能够评估治疗效果的结局指标对于促进囊性纤维化（CF）新治疗药物的研发至关重要。我们研究了通过多次呼吸冲洗（MBW）测量的肺清除指数（LCI）是否能够在24小时内单次给药后检测到高渗盐水（HS）吸入的治疗效果。
在这项随机对照交叉试验中，CF患者吸入HS和等渗盐水（IS）。在24小时内的5个时间点进行MBW和肺功能测定。使用氮气冲洗技术（LCIN2）和六氟化硫作为示踪气体（LCISF6）测量LCI。主要终点是基线和24小时之间LCIN2的变化。次要终点包括LCISF6的变化和肺功能测定结果。
21名患者被随机分组。16名患者完成了所有研究访视和所有时间点的测量。18名患者参与了意向性分析。LCI或肺功能测定结果均未检测到显著变化。然而，主要结局参数（吸入后基线访视和24小时之间LCI的变化）显示，与IS治疗组相比，HS治疗组的LCI有改善趋势，LCIN2为-0.60（标准误0.32），p = 0.08）；肺功能测量未观察到类似趋势。HS的总体效应大小小于先前持续时间更长的研究。
这些数据表明，LCI可能潜在地用作早期试验中的结局指标，用于评估治疗效果大于单次吸入HS的治疗药物。
