McCoy K, Hamilton S, Johnson C
Division of Pulmonary Medicine, Children's Hospital, Columbus, Ohio, USA.
Chest. 1996 Oct;110(4):889-95. doi: 10.1378/chest.110.4.889.
The 12-week efficacy and safety of aerosolized recombinant human DNase (dornase alfa) were evaluated in previously untreated patients with cystic fibrosis (CF) with advanced lung disease.
In this multicenter, double-blind, placebo-controlled study, CF patients with advanced lung disease were randomized to receive either dornase alfa or placebo once a day for 12 weeks.
A total of 320 patients in clinically stable condition with documented CF and an FVC less than 40% of predicted were recruited from 65 CF Foundation care centers in the United States. The dornase alfa and placebo groups were comparable with respect to age (range, 7 to 57 years), height, and weight. Male subjects outnumbered female subjects (55% vs 45%) and few subjects were younger than 17 years of age (15%). The percentages of predicted FEV1 and FVC were significantly lower in the dornase alfa group at baseline (p < or = 0.05).
Patients were randomly assigned to receive either 2.5 mg dornase alfa once daily (n = 158) or placebo once daily (n = 162). All patients continued to receive standard medications and treatments administered for CF.
Dornase alfa improved the mean percent change in FEV1 from baseline by 9.4% compared with 2.1% for placebo (p < 0.001). The actively treated group showed a 12.4% improvement in FVC compared with 7.3% for placebo (p < 0.01). There were no differences between the treatment groups in dyspnea score number of days receiving i.v. antibiotics, or length of hospital stay; the overall incidence of adverse events was comparable between treatment groups. Fifteen patients died: 9 in the dornase alfa group and 6 in the placebo group; no differentiating clinical characteristics were demonstrated.
Pulmonary function as measured by FEV1 and FVC improved significantly in the dornase alfa-treated patients. Dornase alfa was found to be safe and well tolerated over the 12-week study period.
评估雾化重组人脱氧核糖核酸酶（多黏菌素α）对既往未接受治疗的晚期肺部疾病囊性纤维化（CF）患者的12周疗效及安全性。
在这项多中心、双盲、安慰剂对照研究中，晚期肺部疾病CF患者被随机分组，每天接受一次多黏菌素α或安慰剂治疗，为期12周。
从美国65个CF基金会护理中心招募了总共320例临床状况稳定、有CF记录且用力肺活量（FVC）低于预测值40%的患者。多黏菌素α组和安慰剂组在年龄（范围7至57岁）、身高和体重方面具有可比性。男性受试者多于女性受试者（55%对45%），且年龄小于17岁的受试者较少（15%）。多黏菌素α组在基线时预测的第1秒用力呼气容积（FEV1）和FVC百分比显著更低（p≤0.05）。
患者被随机分配，每天接受一次2.5毫克多黏菌素α（n = 158）或安慰剂（n = 162）。所有患者继续接受针对CF的标准药物和治疗。
与安慰剂组的2.1%相比，多黏菌素α使FEV1自基线的平均变化百分比提高了9.4%（p < 0.001）。积极治疗组的FVC改善了12.4%，而安慰剂组为7.3%（p < 0.01）。治疗组在呼吸困难评分、接受静脉注射抗生素的天数或住院时间方面没有差异；治疗组之间不良事件的总体发生率相当。15例患者死亡：多黏菌素α组9例，安慰剂组6例；未显示出有鉴别意义的临床特征。
在接受多黏菌素α治疗的患者中，以FEV1和FVC衡量的肺功能有显著改善。在为期12周的研究期间，发现多黏菌素α安全且耐受性良好。
