马来酸噻吗洛尔外用凝胶治疗浅表型婴幼儿血管瘤的随机双盲前瞻性临床研究

Effect of Timolol Maleate Gel-forming Solution in the Treatment of Superficial Infantile Hemangiomas: a Prospective, Randomized, Double-Blind, Controlled Trial

目的：评估不同浓度马来酸噻吗洛尔凝胶，用于治疗浅表型婴幼儿血管瘤的临床疗效及安全性。方法本研究为随机、双盲的单中心研究。自2012年7月至2013年2月，选取1～6月龄患有浅表型婴幼儿血管瘤的患儿，利用随机量表，分发不同药物浓度的马来酸噻吗洛尔凝胶，进行为期3～6个月的外用药物治疗，以视觉模拟评分法（Visual Analogue Scale，VAS）评价疗效，并记录不良反应；同时，分析临床疗效与患儿的年龄、性别、瘤体部位、瘤体厚度、药物浓度、用药次数和用药时间的相关性。结果使用马来酸噻吗洛尔凝胶治疗后的平均VAS值为30.94±32.97，总治疗有效率62.3%，VAS值与治疗次数、使用时间具有明显的相关性（P＜0.05）。2.9%患儿出现局部皮肤症状，0.97%出现轻度气急现象。结论马来酸噻吗洛尔外用凝胶治疗浅表型婴幼儿血管瘤安全有效，药物浓度并非是提高药效的有效途径。

Objective To investigate the efficacy and safety of timolol maleate gel-forming solution with different concentrations for the treatment of superficial infantile hemangiomas （IHs）. Methods From July 2012 to February 2013, patients aged from 1 to 6 months with superficial infantile hemangiomas were enrolled onto this study：a prospective, randomized, double-blind, controlled trial. Participants were randomly divided into 3 groups according to different concentration of timolol maleate gel-forming solution：group 1 （0.25%timolol gel）, group 2 （0.5%timolol gel） and group 3 （1.0%timolol gel）. Adverse effects and duration of the treatments were recorded. A visual analogue scale （VAS） was used to evaluate the efficacy of the drugs. Multiple logistic regression analysis was used to determine the independent correlation of each factor （e.g. age, gender, tumors location, the thickness of tumor, drug concentration, application frequency and duration of the treatment） and the efficacy. Results The mean VAS score was 30.94±32.97 for the patients treated by timolol gels with a total clinical efficacy of 62.3%. There were significant correlations between the VAS scores and the frequency ＆ the duration of treatment （P〈0.05）. The main side effects were local skin reactions （2.9%） and mild wheezing （0.97%）. Conclusion Timolol gel is safe and effective in the treatment for superficial IHs. Concentrations are not relevant for the treatment effect.