Division of Respiratory Medicine, Department of Pediatrics, and Program in Physiology and Experimental Medicine, SickKids Research Institute, The Hospital for Sick Children, and University of Toronto, Toronto, Canada.
J Cyst Fibros. 2012 Dec;11(6):539-49. doi: 10.1016/j.jcf.2012.05.003. Epub 2012 Jun 8.
Denufosol stimulates chloride secretion independent of the chloride channel which is dysfunctional in cystic fibrosis (CF) and therefore has the potential to benefit CF patients regardless of genotype.
To assess the efficacy of denufosol in CF patients with mild lung function impairment age 5 years and older.
This multicenter, randomized, parallel group double-blind placebo-controlled trial was conducted at 102 CF care centers in Australia, Canada and the United States (NCT00625612) The active group (n=233) received 60 mg denufosol via inhalation three times daily The primary efficacy endpoint was change in FEV(1) in liters from Day 0 to week 48.
685 patients were screened for the study and 466 patients (233 in each group) were randomized to study treatment. The adjusted mean change in FEV(1)was 40 mL for denufosol and 32 mL for placebo with a resulting treatment effect of 8 mL (95% CI -0.040, 0.056). The average rate of change in FEV(1) percent of predicted over 0 to 48 weeks was -3.04% for placebo vs. -2.30 for denufosol (a difference of 24% relative to placebo) among all patients. The incidence of pulmonary exacerbation was 26% vs. 21% for the placebo and denufosol groups with no differences in the time to first event. The study treatments were well tolerated and there was no evidence of systemic effects in any safety parameter assessed.
In patients with CF treatment with denufosol for 48 weeks did not improve pulmonary function or reduce the incidence of pulmonary exacerbations.
地诺前列酮刺激氯离子分泌，而氯离子通道在囊性纤维化（CF）中功能失调，因此无论基因型如何，都有可能使 CF 患者受益。
评估地诺前列酮在 5 岁及以上轻度肺功能损害的 CF 患者中的疗效。
这项多中心、随机、平行组、双盲安慰剂对照试验在澳大利亚、加拿大和美国的 102 个 CF 护理中心进行（NCT00625612）。实验组（n=233）每天接受 60 毫克地诺前列酮吸入治疗，每日 3 次。主要疗效终点为从第 0 天到第 48 周时 FEV1（1 升的呼气量）的变化。
对 685 名患者进行了研究筛选，其中 466 名患者（每组 233 名）被随机分配到研究治疗组。地诺前列酮组 FEV1 的调整平均变化为 40 毫升，安慰剂组为 32 毫升，治疗效果为 8 毫升（95%CI-0.040，0.056）。在所有患者中，0 至 48 周期间 FEV1 预测百分比的平均变化率为安慰剂组为-3.04%，地诺前列酮组为-2.30%（相对于安慰剂组的差异为 24%）。安慰剂组和地诺前列酮组的肺部恶化发生率分别为 26%和 21%，首次事件时间无差异。研究治疗药物耐受性良好，在评估的任何安全性参数中均未发现全身效应的证据。
在 CF 患者中，地诺前列酮治疗 48 周并未改善肺功能或降低肺部恶化的发生率。
