A Phase 2b, Multicenter, Randomized, Double Blind, Placebo-Controlled Clinical Trial to Evaluate the Efficacy of Short-Course Antimicrobial Therapy for Young Children With Acute Otitis Media (AOM) and Impact on Antimicrobial Resistance
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- 入组人数
- 520
- 试验地点
- 2
- 主要终点
- The Distribution of Children Categorized as Treatment Failure (TF) at or Before the Day 12-14 End-of-Treatment Visit Specific to the Index Episode of AOM
研究概览
简要总结
The investigators will study whether, in young children with acute otitis media (AOM), shortening length of antibiotic treatment as a strategy for reducing antimicrobial resistance provides satisfactory clinical outcome. This is a Phase 2b multicenter, randomized, double-blind, placebo-controlled clinical trial in 600 children aged 6 through 23 months comparing the efficacy of consistent reduced-duration antimicrobial treatment (5 days) with that of consistent standard-duration treatment (10 days) for each episode of AOM developing during a single respiratory season (October 1 through May 31).
详细描述
Eligible subjects will be randomized at the enrollment visit and will have a telephone call in the course of therapy, and a subsequent visit at the end of therapy. Thereafter, they will be followed through the end of the respiratory season, and their parents will be encouraged to bring their child when concerned about a potential recurrence of AOM. At each recurrence subjects will receive the treatment regimen (either standard- or reduced-duration) to which they were randomized at study entry (consistent treatment strategy).
The recruitment of eligible children with AOM of varying degrees of severity from various primary care practices in 2 separate geographic regions, i.e. Western Pennsylvania and Kentucky, representing urban, suburban and rural demographics will enhance generalizability of study findings and encourage translation to clinical practice.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •Aged 6 through 23 months
- •Have evidence of AOM defined as:
- •recent (within 48 hours) onset of signs and symptoms as described in the Acute Otitis Media - Severity of Symptoms (AOM-SOS) Scale AND a score of ≥3 at the time of enrollment on the AOM-SOS scale
- •middle ear effusion evidenced by the presence of at least 2 of the following:
- •decreased or absent mobility of the tympanic membrane
- •yellow or white discoloration of the tympanic membrane
- •opacification of the tympanic membrane
- •acute inflammation evidenced by one of the following:
- •1+ bulging of the tympanic membrane with either intense erythema or otalgia
- •2+ or 3+ bulging of the tympanic membrane
- •Has received at least 2 doses of pneumococcal conjugate vaccine
- •Parent has provided informed consent
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 (tympanostomy tubes in place, cleft palate, or Down syndrome)
- •Sensorineural hearing loss (unilateral or bilateral)
- •Serious underlying systemic problems that might obscure response to infection (cystic fibrosis, neoplasm, juvenile diabetes)
- •Concomitant infection that would preclude evaluation of the response of the child's AOM to study product (pneumonia, periorbital cellulitis)
- •Acute wheezing exacerbation which may require treatment with systemic corticosteroids
- •Known renal or hepatic dysfunction or insufficiency
- •History of amoxicillin-clavulanate-associated cholestatic jaundice
- •Immune dysfunction or receipt of immunosuppressive therapy; chronic gastrointestinal conditions (i.e., malabsorption, inflammatory bowel disease)
- •Co-medications (systemic corticosteroids, more than one dose of systemic antimicrobial therapy within 96 hours, receipt of any investigational drug or vaccine within 30 days)
- •Hypersensitivity to penicillin, amoxicillin or amoxicillin-clavulanate, or phenylketonuria or known hypersensitivity to aspartame
- •Unable to complete study, or no access to phone
- •Previously enrolled in this study or currently enrolled in another study
研究组 & 干预措施
Amoxicillin-Clavulanate, 10 days
amoxicillin-clavulanate, 90/6.4 mg/kg/day, 2 divided doses, 10 days
干预措施: Amoxicillin-Clavulanate, 10 days (Drug)
Amoxicillin-Clavulanate, 5 days
amoxicillin-clavulanate, 90/6.4 mg/kg/day, 2 divided doses, 5 days plus placebo, 2 divided doses, 5 days
干预措施: Amoxicillin-Clavulanate, 5 days (Drug)
结局指标
主要结局
The Distribution of Children Categorized as Treatment Failure (TF) at or Before the Day 12-14 End-of-Treatment Visit Specific to the Index Episode of AOM
时间窗: From 72 hours after randomization until day 21 of the index episode. The mean day for this visit was 13.2.
Proportion of children initially diagnosed with AOM who experience treatment failure at or before the day 12-14 visit. TF is defined as substantial persistence or worsening of symptoms specifically attributable to AOM, or of otoscopic signs of AOM, after 72 hours from the time of randomization, such that additional antimicrobial therapy is deemed advisable. If a parent/legal guardian is unwilling to continue the assigned study product regimen, the participant will be categorized as TF. Should a participant be administered another systemic antibiotic while taking study medication or prior to Day 16, the participant will be considered a TF. Clinical success is defined as complete or substantial resolution of symptoms specifically attributable to AOM for 48 hours and of otoscopic signs of acute inflammation (bulging of the tympanic membrane (TM) or intense erythema), with or without persistence of middle-ear effusion, such that no additional antibiotic therapy is deemed advisable.
次要结局
- The Distribution of AOM Recurrences Categorized as Treatment Failure (TF) at or Before the Day 12-14 End-of-Treatment Visit(From 72 hours after the AOM recurrence was diagnosed until day 21 of the recurrence. The mean day for this visit was 13.3.)
- The Distribution of AOM Recurrences With a Nasopharyngeal (NP) Culture at Onset That is Positive for One or More Nonsusceptible Pathogens in Which the Follow-up NP Culture at Day 12-14 Yields a Nonsusceptible Pathogen(The end-of-treatment visit. The mean day for this visit was 13.4.)
- The Distribution of Children With a Nasopharyngeal (NP) Culture at Enrollment That is Negative for AOM Pathogens in Which the Follow-up NP Culture at Day 12-14 Yields a Nonsusceptible Pathogen(The day 12-14 visit. The mean day for this visit was 13.3.)
- The Distribution of AOM Recurrences for Which the Follow-up Nasopharyngeal (NP) Culture at the Day 12-14 Visit Yields a Nonsusceptible Streptococcus Pneumoniae (S pn) Isolate(The day 12-14 visit following a recurrence. The mean day for this visit was 13.6.)
- The Distribution of Children With AOM Recurrences and Relapses Within 60 Days of Enrollment(Day 1 of study entry until day 60.)
- The Distribution of Children With AOM Recurrences and Relapses Within the Entire Respiratory Season(Day 1 of study entry until day 244. The respiratory season is October 1 - May 31, inclusive.)
- The Mean Rate, Per Month, of Protocol AOM Recurrences and Relapses Within 60 Days of Enrollment(Day 1 of study entry until day 60.)
- The Distribution of AOM Recurrences With a Nasopharyngeal (NP) Culture at Onset That is Negative for AOM Pathogens in Which the Follow-up NP Culture at Day 12-14 Yields a Nonsusceptible Pathogen(The day 12-14 visit. The mean day for this visit was 13.4.)
- The Distribution of Children With a Nasopharyngeal (NP) Culture at Enrollment That is Positive Only for One or More Susceptible Pathogens in Which the Follow-up NP Culture at Day 12-14 Yields a Nonsusceptible Pathogen(The day 12-14 visit. The mean day for this visit was 13.2.)
- The Distribution of AOM Recurrences With a Nasopharyngeal (NP) Culture at Onset That is Positive Only for One or More Susceptible Pathogens in Which the Follow-up NP Culture at Day 12-14 Yields a Nonsusceptible Pathogen(The day 12-14 visit. The mean day for this visit was 13.9.)
- The Distribution of Children With a Nasopharyngeal (NP) Culture at Enrollment That is Positive for One or More Nonsusceptible Pathogens in Which the Follow-up NP Culture at Day 12-14 Yields a Nonsusceptible Pathogen(The end-of-treatment visit. The mean day for this visit was 13.6.)
- The Distribution of AOM Recurrences for Which the Follow-up Nasopharyngeal (NP) Culture at the Day 12-14 Visit Yields a Nonsusceptible Haemophilus Influenzae (H Flu) Isolate(The day 12-14 visit following a recurrence. The mean day for this visit was 13.6.)
- The Distribution of Children Whose Nasopharyngeal (NP) Isolates at Enrollment Are Pathogen Negative or Positive Only for at Least One Susceptible Pathogen Who Become Colonized With Nonsusceptible Pathogens at Any Time Over the Course of Follow-up(Day 1 of study entry until day 365)
- The Distribution of 6 Week Follow-up, Non-Illness Visits During the Respiratory Season at Which a Nonsusceptible Pathogen is Recovered(Day 1 of study entry until day 244. The respiratory season is October 1 - May 31, inclusive.)
- The Distribution of Children for Whom the Follow-up Nasopharyngeal (NP) Culture at the Day 12-14 Visit, Specific to the Index Episode, Yields a Nonsusceptible Streptococcus Pneumoniae (S pn) Isolate(The day 12-14 visit specific to the index episode. The mean day for this visit was 13.4.)
- The Distribution of Children for Whom the Follow-up Nasopharyngeal (NP) Culture at the Day 12-14 Visit, Specific to the Index Episode, Yields a Nonsusceptible Haemophilus Influenzae (H Flu) Isolate(The day 12-14 visit specific to the index episode. The mean day for this visit was 13.4.)
- The Mean Rate, Per Month, of Protocol AOM Recurrences and Relapses Within the Entire Respiratory Season(Day 1 of study entry until day 244. The respiratory season is October 1 - May 31, inclusive.)
- The Mean Number of Days Systemic Antibiotics Were Received During the Entire Respiratory Season(Day 1 of study entry until day 244. The respiratory season is October 1 - May 31, inclusive.)
- The Mean Acute Otitis Media - Severity of Symptom (AOM-SOS) Scores Days 6 to 14(From day 6 of administration of study product until day 14 for all episodes)
- The Distribution of Children for Whom Protocol-Defined Diarrhea (PDD) Was Reported and Associated With Study Product(Day 1 of administration of study product until day 16 for all episodes)
- The Distribution of Children for Whom Diaper Dermatitis Was Reported and Associated With Study Product(Day 1 of administration of study product until day 16 for all episodes)
研究者
Alejandro Hoberman
Professor of Pediatrics
University of Pittsburgh