The Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ontario, Canada.
PLoS One. 2012;7(4):e36077. doi: 10.1371/journal.pone.0036077. Epub 2012 Apr 30.
Many patients with cystic fibrosis develop persistent airway infection/colonization with Aspergillus fumigatus, however the impact of A. fumigatus on clinical outcomes remains unclear. The objective of this study was to determine whether treatment directed against Aspergillus fumigatus improves pulmonary function and clinical outcomes in patients with cystic fibrosis (CF).
We performed a double-blind randomized placebo-controlled pilot clinical trial involving 35 patients with CF whose sputum cultures were chronically positive for A. fumigatus. Participants were centrally randomized to receive either oral itraconazole 5 mg/kg/d (N = 18) or placebo (N = 17) for 24 weeks. The primary outcome was the proportion of patients who experienced a respiratory exacerbation requiring intravenous antibiotics over the 24 week treatment period. Secondary outcomes included changes in FEV(1) and quality of life.
Over the 24 week treatment period, 4 of 18 (22%) patients randomized to itraconazole experienced a respiratory exacerbation requiring intravenous antibiotics, compared to 5 of 16 (31%) placebo treated patients, P = 0.70. FEV(1) declined by 4.62% over 24 weeks in the patients randomized to itraconazole, compared to a 0.32% improvement in the placebo group (between group difference = -4.94%, 95% CI: -15.33 to 5.45, P = 0.34). Quality of life did not differ between the 2 treatment groups throughout the study. Therapeutic itraconazole blood levels were not achieved in 43% of patients randomized to itraconazole.
We did not identify clinical benefit from itraconazole treatment for CF patients whose sputum was chronically colonized with A. fumigatus. Limitations of this pilot study were its small sample size, and failure to achieve therapeutic levels of itraconazole in many patients.
ClinicalTrials.gov NCT00528190.
许多囊性纤维化患者会持续发生气道曲霉属感染/定植，然而曲霉属对临床结果的影响尚不清楚。本研究的目的是确定针对烟曲霉的治疗是否能改善囊性纤维化（CF）患者的肺功能和临床结果。
我们进行了一项双盲、随机、安慰剂对照的试点临床试验，纳入了 35 例痰液持续培养为烟曲霉阳性的 CF 患者。参与者采用中央随机化方法，接受每日 5mg/kg 的口服伊曲康唑（N=18）或安慰剂（N=17）治疗 24 周。主要结局是在 24 周治疗期间经历需要静脉使用抗生素的呼吸恶化的患者比例。次要结局包括 FEV1 和生活质量的变化。
在 24 周的治疗期间，随机接受伊曲康唑治疗的 18 例患者中有 4 例（22%）发生需要静脉使用抗生素的呼吸恶化，而接受安慰剂治疗的 16 例患者中有 5 例（31%），P=0.70。随机接受伊曲康唑治疗的患者的 FEV1 在 24 周内下降了 4.62%，而安慰剂组则改善了 0.32%（组间差异为-4.94%，95%CI：-15.33 至 5.45，P=0.34）。在整个研究过程中，两组的生活质量没有差异。随机接受伊曲康唑治疗的患者中，有 43%未达到伊曲康唑的治疗血药浓度。
我们没有发现伊曲康唑治疗持续被烟曲霉定植的 CF 患者的临床获益。这项试点研究的局限性在于样本量小，以及许多患者未能达到伊曲康唑的治疗血药浓度。
ClinicalTrials.gov NCT00528190。
