Reduced Clavulanate Formulation of Amoxicillin-Clavulanate in Children 6-23 Months With Acute Otitis Media
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 112
- 试验地点
- 1
- 主要终点
- The Distribution of Participants Receiving Formulation 1 for Whom Diaper Dermatitis Was Reported and Associated With Study Product
研究概览
简要总结
To evaluate the safety profile of amoxicillin-clavulanate potassium containing a reduced concentration of clavulanate potassium, 600 mg/21.5 mg/5 mL (a ratio of 28:1), administered at 90/3.2 mg/kg/day (formulation 1) or at 80/2.85 mg/kg/day (formulation 2) in two divided doses for 10 days. Investigators will focus on the proportion of subjects who develop protocol-defined diarrhea and proportion who develop diaper dermatitis that occasions the prescription of antifungal medication.
详细描述
Amoxicillin-clavulanate potassium has been shown to be efficacious in eradicating causative pathogens in acute otitis media (AOM) with resulting high clinical cure rates at end-of-treatment (85%). However, relatively high rates (~25%) of clinically significant diarrhea have been reported, the occurrence of which has been directly related to the clavulanate potassium component of the drug combination. A reduced concentration of clavulanate potassium in the drug formulation would be expected to have an improved safety profile regarding the occurrence of diarrhea. This study will examine whether the concentration of the clavulanate potassium component of amoxicillin-clavulanate potassium could be reduced in the treatment of children 6 months through 23 months of age diagnosed with AOM using stringent criteria. A total of 75 participants (n=75) with AOM will receive amoxicillin-clavulanate potassium (600 mg/21.5 mg/5 mL; 28:1) administered at 90/3.2 mg/kg/day (formulation 1) or at 80/2.85 mg/kg/day (formulation 2) in two divided doses for 10 days.
The primary outcome measure will be rates of clinically significant diarrhea and diaper dermatitis. These rates will be compared with the rate observed in our previous studies of AOM in children who received amoxicillin-clavulanate potassium (600 mg/42.9 mg/5 mL; 14:1) administered at 90/6.4 mg/kg/day in two divided doses for 10 days.
A subset of this group will have pharmacokinetic studies performed. Each participant that agrees will have a single blood draw (n=50). Investigators will analyze amoxicillin and clavulanate potassium in the blood samples using validated methods.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 6 Months 至 23 Months（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age range: 6 to 23 months
- •Evidence of AOM
- •Recent (within 48 hours) onset of signs and symptoms.
- •Middle ear effusion evidenced by the presence of at least 2 of the following: decreased or absent mobility of the tympanic membrane (TM), yellow of white discoloration of the TM, and/or opacification of the TM
- •Acute inflammation evidenced by one of the following: 1+ bulging of the TM with either intense erythema or otalgia or 2+ or 3+ bulging of the TM
排除标准
- •Toxic appearance (capillary refill >3 seconds, systolic blood pressure <60 mm Hg)
- •Inpatient hospitalization
- •Clinical or anatomical characteristics that might obscure response to treatment (e.g., tympanostomy tubes in place, cleft palate, Down syndrome)
- •Sensorineural hearing loss (unilateral or bilateral)
- •Allergy to amoxicillin or amoxicillin clavulanate
- •Recent treatment of AOM within the last 14 days
研究组 & 干预措施
amoxicillin-clavulanate potassium
amoxicillin-clavulanate potassium (600 mg/221.5 mg/5 mL; 28:1) administered prior to February 25, 2016 at 90/3.2 mg/kg/day in two divided doses for 10 days; oral, liquid (formulation 1) or administered as of February 25, 2016 at 80/2.85 mg/kg/day in two divided doses for 10 days; oral, liquid (formulation 2)
干预措施: Amoxicillin-Clavulanate potassium (Drug)
结局指标
主要结局
The Distribution of Participants Receiving Formulation 1 for Whom Diaper Dermatitis Was Reported and Associated With Study Product
时间窗: Day 1 of administration of amoxicillin-clavulanate until day 12.
Participants receiving formulation 1 were administered amoxicillin-clavulanate potassium containing a reduced concentration of clavulanate potassium, 600 mg/21.5 mg/5 mL (a ratio of 28:1), administered at 90/3.2 mg/kg/day in two divided doses for 10 days. Diaper dermatitis is defined as dermatitis in the diaper area calling for prescription of a topical antifungal agent and is limited to events associated with study product.
The Distribution of Participants Receiving Formulation 2 for Whom Diaper Dermatitis Was Reported and Associated With Study Product
时间窗: Day 1 of administration of amoxicillin-clavulanate until day 12.
Participants receiving formulation 2 were administered amoxicillin-clavulanate potassium containing a reduced concentration of clavulanate potassium, 600 mg/21.5 mg/5 mL (a ratio of 28:1), administered at 80/2.85 mg/kg/day in two divided doses for 10 days. Diaper dermatitis is defined as dermatitis in the diaper area calling for prescription of a topical antifungal agent and is limited to events associated with study product..
The Distribution of Participants Receiving Formulation 1 for Whom Protocol-Defined Diarrhea (PDD) Was Reported and Associated With Study Product
时间窗: Day 1 of administration of amoxicillin-clavulanate until day 12.
Participants receiving formulation 1 were administered amoxicillin-clavulanate potassium containing a reduced concentration of clavulanate potassium, 600 mg/21.5 mg/5 mL (a ratio of 28:1), administered at 90/3.2 mg/kg/day in two divided doses for 10 days. Protocol-defined diarrhea is defined as the occurrence of three or more watery stools in 1 day or two watery stools daily for 2 consecutive days and is limited to events associated with study product.
The Distribution of Participants Receiving Formulation 2 for Whom Protocol-Defined Diarrhea (PDD) Was Reported and Associated With Study Product
时间窗: Day 1 of administration of amoxicillin-clavulanate until day 12.
Participants receiving formulation 2 were administered amoxicillin-clavulanate potassium containing a reduced concentration of clavulanate potassium, 600 mg/21.5 mg/5 mL (a ratio of 28:1), administered at 80/2.85 mg/kg/day in two divided doses for 10 days. Protocol-defined diarrhea is defined as the occurrence of three or more watery stools in 1 day or two watery stools daily for 2 consecutive days and is limited to events associated with study product.
次要结局
- The Distribution of Participants Receiving Formulation 2 Categorized as Treatment Failure (TF) at or Before the End-of-Treatment Visit(From 72 hours after the initial AOM until the end-of-treatment visit. The mean day for this visit was 13.9.)
- The Distribution of Participants Receiving Formulation 1 Categorized as Treatment Failure (TF) at or Before the End-of-Treatment Visit(From 72 hours after the initial AOM until the end-of-treatment visit. The mean day for this visit was 14.9.)
- The Mean Score Representing the Parent or Guardian's Level of Satisfaction With Therapy for Participants Receiving Formulation 2(The end-of-treatment visit. The mean day for this visit was 13.9.)
- The Distribution of Participants Receiving Formulation 1 Demonstrating Resolution of Acute Otitis Media (AOM) and Substantial Improvement of Symptoms That Would Allow Discontinuing Therapy at the Day 7 Visit(Day 1 of administration of amoxicillin-clavulanate until the day 7 visit. The mean day for this visit was 7.5.)
- The Distribution of Participants Receiving Formulation 2 Demonstrating Resolution of Acute Otitis Media (AOM) and Substantial Improvement of Symptoms That Would Allow Discontinuing Therapy at the Day 7 Visit(Day 1 of administration of amoxicillin-clavulanate until the day 7 visit. The mean day for this visit was 7.6.)
- The Mean Score Representing the Parent or Guardian's Level of Satisfaction With Therapy for Participants Receiving Formulation 1(The end-of-treatment visit. The mean day for this visit was 14.9.)
- Distribution of Population Plasma Concentration of Amoxicillin According to Time For Participants Receiving Formulation 1(From administration of a single dose of amoxicillin-clavulanate until approximately 4 hours after.)
- Distribution of Population Plasma Concentration of Amoxicillin According to Time For Participants Receiving Formulation 2(From administration of a single dose of amoxicillin-clavulanate until approximately 4 hours after.)
- Distribution of Population Plasma Concentration of Clavulanate According to Time For Participants Receiving Formulation 1(From administration of a single dose of amoxicillin-clavulanate until approximately 4 hours after.)
- Distribution of Population Plasma Concentration of Clavulanate According to Time For Participants Receiving Formulation 2(From administration of a single dose of amoxicillin-clavulanate until approximately 4 hours after.)
研究者
Nader Shaikh
Associate Professor of Pediatrics
University of Pittsburgh