Center for Pediatric ENT-Head and Neck Surgery, Boynton Beach, Florida.
Otolaryngology Department, Hospital Vall d'Hebron, Barcelona, Spain.
JAMA Otolaryngol Head Neck Surg. 2017 Apr 1;143(4):341-349. doi: 10.1001/jamaoto.2016.3537.
Acute otitis media with tympanostomy tubes (AOMT) in children commonly presents with otorrhea and negatively affects their daily activities.
To evaluate the efficacy and safety of topical ciprofloxacin, 0.3%, plus fluocinolone acetonide, 0.025%, otic solution relative to ciprofloxacin, 0.3%, otic solution alone and fluocinolone acetonide, 0.025%, otic solution alone in the treatment of AOMT in children.
DESIGN, SETTING, AND PARTICIPANTS: Two twin multicenter, randomized, double-blind clinical trials with identical designs were conducted from June 24, 2011, through June 23, 2014, at ear, nose, and throat pediatric practices, general practices, hospitals, and clinical research centers. The study population comprised 662 children (331 in each trial) with AOMT in at least 1 ear who presented with moderate or severe purulent otorrhea for 3 weeks or less. Data analyses were performed on an intention-to-treat basis.
Patients were randomly assigned to receive ciprofloxacin plus fluocinolone, ciprofloxacin alone, or fluocinolone alone twice daily for 7 days and were evaluated on days 1 (baseline), 3 to 5 (undergoing therapy), 8 to 10 (end of therapy), and 18 to 22 (test of cure).
The primary efficacy measure was time to cessation of otorrhea. The principal secondary end point was sustained microbiological cure, defined as eradication or presumed eradication at end-of-therapy and test-of-cure visits.
A total of 662 children participating in the 2 studies were randomized to receive ciprofloxacin plus fluocinolone (n = 223), ciprofloxacin alone (n = 221), or fluocinolone alone (n = 218). The median age was 2.5 years (range, 0.6-12.7 years). The median time to cessation of otorrhea was 4.23 days (95% CI, 3.65-4.95 days) in patients receiving ciprofloxacin plus fluocinolone compared with 6.95 days (95% CI, 5.66-8.20 days) in those receiving ciprofloxacin and not estimable findings in those receiving fluocinolone alone (P < .001). The clinical cure rate at the test-of-cure visit was 80.6% in the ciprofloxacin plus fluocinolone group, 67.4% in the ciprofloxacin group (difference, 13.2%; 95% CI, 5.0%-21.4%; P = .002), and 47.6% in the fluocinolone group (difference, 33.0%; 95% CI, 24.0%-42.0%; P < .001). The sustained microbiological cure rate was 79.7% in the ciprofloxacin plus fluocinolone group vs 67.7% in the ciprofloxacin group (difference, 12.0%; 95% CI, 0.8%-23.0%; P = .04) and 37.6% in the fluocinolone group (difference, 42.1%; 95% CI, 29.3%-54.8%; P < .001). Only 7 (3.1%) of the patients receiving ciprofloxacin plus fluocinolone, 8 (3.6%) of the patients receiving ciprofloxacin, and 10 (4.7%) of the patients receiving fluocinolone presented with adverse events related to study medication.
The combination of ciprofloxacin plus fluocinolone is more effective than treatment with ciprofloxacin or fluocinolone alone for AOMT, and it is safe and well tolerated in children.
clinicaltrials.gov Identifiers: NCT01395966 and NCT01404611.
重要性：儿童患有伴有鼓膜切开术的急性中耳炎（AOMT）通常表现为耳漏，并对其日常生活活动产生负面影响。
目的：评估环丙沙星 0.3%加氟轻松醋酸酯 0.025%滴耳液与单独使用环丙沙星 0.3%滴耳液和单独使用氟轻松醋酸酯 0.025%滴耳液治疗儿童 AOMT 的疗效和安全性。
设计、地点和参与者：这是两项双胞胎多中心、随机、双盲临床试验，设计完全相同，于 2011 年 6 月 24 日至 2014 年 6 月 23 日在耳鼻喉科儿科诊所、普通科诊所、医院和临床研究中心进行。研究人群包括 662 名患有至少 1 耳 AOMT 的儿童（每个试验 331 名），这些儿童的中度或重度脓性耳漏持续时间为 3 周或更短。数据分析采用意向治疗分析。
干预措施：患者被随机分配接受环丙沙星加氟轻松、环丙沙星单独或氟轻松单独治疗，每天 2 次，共 7 天，并在第 1 天（基线）、第 3-5 天（治疗期间）、第 8-10 天（治疗结束）和第 18-22 天（治愈测试）进行评估。
主要结果和措施：主要疗效指标是耳漏停止的时间。主要次要终点是持续的微生物学治愈，定义为在治疗结束和治愈测试访视时的根除或假定根除。
结果：共有 662 名参与这两项研究的儿童被随机分配接受环丙沙星加氟轻松（n=223）、环丙沙星单独治疗（n=221）或氟轻松单独治疗（n=218）。中位年龄为 2.5 岁（范围，0.6-12.7 岁）。与接受环丙沙星治疗的患者相比，接受环丙沙星加氟轻松治疗的患者中位耳漏停止时间为 4.23 天（95%CI，3.65-4.95 天），而接受环丙沙星治疗的患者为 6.95 天（95%CI，5.66-8.20 天），接受氟轻松单独治疗的患者无法估计（P<.001）。在治愈测试访视时，环丙沙星加氟轻松组的临床治愈率为 80.6%，环丙沙星组为 67.4%（差异为 13.2%；95%CI，5.0%-21.4%；P=.002），氟轻松组为 47.6%（差异为 33.0%；95%CI，24.0%-42.0%；P<.001）。环丙沙星加氟轻松组的持续微生物学治愈率为 79.7%，环丙沙星组为 67.7%（差异为 12.0%；95%CI，0.8%-23.0%；P=.04），氟轻松组为 37.6%（差异为 42.1%；95%CI，29.3%-54.8%；P<.001）。只有 7 名（3.1%）接受环丙沙星加氟轻松的患者、8 名（3.6%）接受环丙沙星的患者和 10 名（4.7%）接受氟轻松的患者出现与研究药物相关的不良事件。
结论和相关性：环丙沙星加氟轻松联合治疗对儿童 AOMT 的疗效优于单独使用环丙沙星或氟轻松，且安全性和耐受性良好。
试验注册：clinicaltrials.gov 标识符：NCT01395966 和 NCT01404611。
