采用改良工艺制备的妥布霉素吸入粉在囊性纤维化中的随机 EDIT 试验。
Tobramycin inhalation powder manufactured by improved process in cystic fibrosis: the randomized EDIT trial.
机构信息
Pediatric Clinic, UMHAT Alexandrovska, Sofia, Bulgaria.
出版信息
Curr Med Res Opin. 2013 Aug;29(8):947-56. doi: 10.1185/03007995.2013.805122. Epub 2013 Jun 5.
BACKGROUND
Tobramycin inhalation powder (TIP) was reported to be effective in two Phase III studies in patients with cystic fibrosis (CF) chronically infected with Pseudomonas aeruginosa (Pa). The EDIT study evaluated the efficacy and safety of TIP manufactured by an improved process in CF subjects aged 6-21 years.
METHODS
CF patients with a forced expiratory volume in 1 second (FEV₁) ≥25% to ≤80% predicted, positive Pa cultures and inhaled antipseudomonal therapy naïve (or at least for past 4 months) were enrolled into this double-blind, multicenter trial. Patients were randomized to receive TIP or placebo (1:1) twice daily for one treatment cycle (28.5 days on drug, 28 days off drug). The primary endpoint was relative change in FEV₁ percentage predicted from baseline to day 29. A pre-specified sensitivity analysis evaluated absolute change in FEV₁% predicted. Other endpoints included Pa sputum density and safety.
RESULTS
A total of 62 patients out of a target of 100 (mean age 12.9 years, baseline FEV₁ 59.2% predicted, Pa sputum density 7.4 log₁₀ colony forming units [CFU] per gram) were randomized. Mean treatment differences (TIP - placebo) were 5.9% (p=0.148) and 4.4% (p<0.05) for relative and absolute change in FEV₁% predicted respectively. TIP significantly reduced Pa sputum density by -1.2 log10 CFU (p=0.002). Treatment with TIP was well tolerated.
CONCLUSIONS
Relative change in FEV₁% predicted with TIP treatment was in the expected range based on the literature, but did not reach statistical significance versus placebo. Placebo control and use of treatment naïve patients led to significant recruitment challenges and an underpowered study with consequent impact on the generated data. However, significant improvements in other outcomes including absolute change in FEV₁% predicted and reduction in Pa sputum density indicate that TIP is efficacious and well tolerated in CF patients. CLINICALTRIALS.GOV IDENTIFIER: NCT00918957.
背景
妥布霉素吸入粉（TIP）在两项 III 期研究中被报道对慢性铜绿假单胞菌（Pa）感染的囊性纤维化（CF）患者有效。EDIT 研究评估了改良工艺制造的 TIP 在 6-21 岁 CF 患者中的疗效和安全性。
方法
本双盲、多中心试验纳入了用力呼气量第一秒（FEV₁）≥25%至≤80%预计值、Pa 培养阳性且无吸入性抗假单胞菌治疗（或至少过去 4 个月无治疗）的 CF 患者。患者被随机分为每日两次接受 TIP 或安慰剂（1:1）治疗一个治疗周期（用药 28.5 天，停药 28 天）。主要终点为从基线到第 29 天 FEV₁预计值的相对变化。一项预设的敏感性分析评估了 FEV₁%预计值的绝对变化。其他终点包括 Pa 痰密度和安全性。
结果
在目标 100 名患者中，共有 62 名患者（平均年龄 12.9 岁，基线 FEV₁ 59.2%预计值，Pa 痰密度 7.4log₁₀ 菌落形成单位[CFU]每克）被随机分组。FEV₁%预计值的 TIP 与安慰剂治疗的平均差值分别为 5.9%（p=0.148）和 4.4%（p<0.05）。TIP 显著降低了 Pa 痰密度-1.2log10 CFU（p=0.002）。TIP 治疗耐受性良好。
结论
TIP 治疗的 FEV₁%预计值的相对变化在文献报道的范围内，但与安慰剂相比无统计学意义。安慰剂对照和使用治疗初治患者导致了显著的招募挑战和研究能力不足，从而对产生的数据产生了影响。然而，其他结局（包括 FEV₁%预计值的绝对变化和 Pa 痰密度的降低）的显著改善表明 TIP 在 CF 患者中是有效且耐受良好的。临床试验注册号：NCT00918957。
Zotero 插件