Santos Felipe, Shu Edina, Lee Daniel J, Jung David H, Quesnel Alicia M, Stankovic Konstantina M, Abdul-Aziz Dunia E, Bay Camden P, Quinkert Amy, Welling D Bradley
Department of Otolaryngology Head and Neck Surgery Harvard Medical School Boston Massachusetts USA.
Department of Infectious Disease Massachusetts Eye and Ear and Massachusetts General Hospital Boston Massachusetts USA.
Laryngoscope Investig Otolaryngol. 2020 May 14;5(4):657-664. doi: 10.1002/lio2.395. eCollection 2020 Aug.
To determine the efficacy of fibroblast growth factor-2 (FGF-2) in treating chronic nonhealing tympanic membrane (TM) perforations.
Double-blinded, randomized placebo controlled phase 2 clinical trial for patients with chronic TM perforations of more than 3 months duration with a cross-over arm. Patients received either FGF-2 or placebo (sterile water) saturated gelatin sponge in the perforation after rimming the perforation under topical anesthesia. The perforation was then covered with Tisseel fibrin glue. The primary endpoint was complete closure of the TM perforation. Secondary end points included change in hearing and partial TM closure rates. The TM was examined every 3 weeks with otoendoscopy for closure. The treatment was repeated if there was incomplete closure every 3 weeks up to a total of three treatments per arm.
Seventy four patients were recruited for the study. Fifty seven met eligibility criteria and fifty four completed the study. Ten of 14 perforations closed completely in the placebo group (71.4%) and 23 of 40 perforations closed completely in the FGF-2 treatment group (57.5%), value = .36. Pure tone averages and word recognition scores were not statistically significantly different between study groups post-treatment. After initial complete closure, re-perforation occurred in seven FGF-2 treated patients and two placebo patients making the effective final closure rate 40% for FGF and 57% for placebo, respectively.
No statistically significant difference in tympanic membrane perforation closure rate was found between the FGF-2 and placebo groups. There were no differences in hearing outcomes between the groups.
1b.
确定成纤维细胞生长因子-2（FGF-2）治疗慢性不愈合鼓膜穿孔的疗效。
对病程超过3个月的慢性鼓膜穿孔患者进行双盲、随机、安慰剂对照的2期临床试验，并设有交叉组。患者在局部麻醉下将穿孔边缘修整后，在穿孔处接受FGF-2或安慰剂（无菌水）饱和明胶海绵治疗。然后用Tisseel纤维蛋白胶覆盖穿孔。主要终点是鼓膜穿孔完全闭合。次要终点包括听力变化和鼓膜部分闭合率。每3周用耳内镜检查鼓膜是否闭合。如果未完全闭合，每3周重复治疗一次，每组最多治疗三次。
74例患者被纳入研究。57例符合入选标准，54例完成研究。安慰剂组14个穿孔中有10个完全闭合（71.4%），FGF-2治疗组40个穿孔中有23个完全闭合（57.5%），P值=0.36。治疗后研究组之间的纯音平均值和单词识别分数无统计学显著差异。最初完全闭合后，7例接受FGF-2治疗的患者和2例安慰剂治疗的患者出现再次穿孔，FGF和安慰剂的最终有效闭合率分别为40%和57%）。
FGF-2组和安慰剂组在鼓膜穿孔闭合率上无统计学显著差异。两组听力结果无差异。
1b。
