Clinical trial NCT02554383: Efficacy of Antibiotics in Children With Acute Sinusitis: Which Subgroups Benefit?
Official title: Efficacy of Antibiotics in Children With Acute Sinusitis: Which Subgroups Benefit?
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Sinusitis
Respiratory Tract Infections
Keywords: pediatrics
antibiotics
placebo
Lead sponsor: University of Pittsburgh
Sponsor class: OTHER
Collaborators: name: National Institute of Allergy and Infectious Diseases (NIAID)
First posted: 2015-09-18
Enrollment: 515
Sex: ALL
Minimum age (years): 2
Maximum age (years): 11
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The objective of this trial is to determine whether certain subgroups of children with acute sinusitis exist in whom antibiotic therapy can be appropriately withheld.

Detailed description: The current clinical practice guideline from the American Academy of Pediatrics for the Diagnosis and Management of Acute Bacterial Sinusitis recommends that the diagnosis of acute sinusitis is made when symptoms of an upper respiratory infection (URI) persist beyond 10 days without showing signs of improvement (persistent presentation), when symptoms appear to worsen (on the 6th to 10th day) after a period of improvement (worsening presentation), or when both high fever and purulent nasal discharge are present concurrently for at least 3 consecutive days (severe presentation). In studies to date, children with persistent and worsening presentations comprise \>95% of cases. The investigators preliminary data and the available literature suggest that only a subset of children being diagnosed with acute sinusitis on the basis of current criteria are likely to have bacterial disease. This is not entirely surprising because current criteria rely solely on the duration and the quality of respiratory tract symptoms (which are both common and non-specific). Accordingly, it seems likely that many children currently being diagnosed as having acute sinusitis actually have an uncomplicated upper respiratory infection. This is important because acute sinusitis is one of the most common diagnoses for which antimicrobials are prescribed for children in the United States, accounting for 7.9 million prescriptions annually. A critical need thus exists to establish which subgroups of children currently being diagnosed with acute sinusitis actually benefit from antimicrobial therapy.

The objective of this trial is to determine whether certain subgroups of children with acute sinusitis exist in whom antibiotic therapy can be appropriately withheld. This objective will be achieved by conducting a large, randomized, double-blind, placebo-controlled clinical trial in children 2 to 12 years of age with persistent or worsening presentations of acute sinusitis. Based on the investigators preliminary data, the investigators hypothesize that only certain subgroups of children currently being treated for acute sinusitis actually benefit from antimicrobial therapy. By identifying, in a large placebo-controlled trial, subgroups of children who respectively do and do not benefit from antimicrobial therapy, the investigators will be better able to determine which children should be classified as having acute bacterial sinusitis. Accordingly, the results of this trial may impact not only the treatment guidelines for acute sinusitis but also the diagnostic criteria, and will help ensure that, to the extent possible, antibiotic use is limited to appropriate patients. This, in turn, will maximize the likelihood of achieving optimal outcomes and minimize the risk of promoting antibiotic resistance.

Eligibility criteria: Inclusion Criteria:

* Meets criteria for "persistent" or "worsening" presentations of sinusitis
* Baseline score ≥9 on the Pediatric Rhinosinusitis Symptom Scale

Exclusion Criteria:

* Severe presentation (≥3 days of colored nasal discharge and fever ≥39°C
* Asthma/allergic rhinitis explains symptoms
* Allergy to amoxicillin-clavulanate
* Immotile cilia syndrome
* Cystic fibrosis
* Immunodeficiency
* Parental inability to read/write English or Spanish
* Other concurrent infection (e.g., pneumonia, acute otitis media, streptococcal pharyngitis)
* Systemic toxicity
* Wheezing on exam
* Antibiotic use within 15 days

Primary outcomes:
measure: The Mean Pediatric Rhinosinusitis Symptom Scale (PRSS) Score Over the First 10 Days of Follow-up According to the Presence of Pathogens in the Nasopharynx at Enrollment
timeFrame: Days 2 to 11
measure: The Mean Pediatric Rhinosinusitis Symptom Scale (PRSS) Score Over the First 10 Days of Follow-up According to the Presence of Colored Nasal Discharge at Enrollment
timeFrame: Days 2 to 11
Secondary outcomes:
measure: The Distribution of Children Experiencing Treatment Failure (TF)
timeFrame: Day of enrollment to the day of the follow-up visit. The mean length of actual follow-up was 13.4 days. For each child with incomplete follow-up, multiple imputation was used and PRSS scores for the remaining days were imputed.
measure: The Distribution of Children Developing Acute Otitis Media (AOM) Over the First 10 Days of Follow-up
timeFrame: Days 2 to 11, where Day 1 is day of enrollment. The mean number of days of follow-up in this interval was 9.8.
measure: The Distribution of Children Receiving a Systemic Antibiotic Over the First 10 Days of Follow-up
timeFrame: Days 2 to 11, where Day 1 is day of enrollment. The mean number of days of follow-up in this interval was 9.8.
measure: The Distribution of Children for Whom Diarrhea or Generalized Rash Was Reported
timeFrame: Day 1 through Day 23.
measure: The Distribution of Children Compliant With Study Medication
timeFrame: Days 1 to 11, where Day 1 is day of enrollment
Other outcomes:
measure: The Distribution of Children With a Nonsusceptible Pathogen at the Follow-up Visit
timeFrame: The follow-up visit. The mean number of days from enrollment to the follow-up visit was 13.4.
Locations:
city: Bardstown
country: United States
facility: Kentucky Pediatric/Adult Research
state: Kentucky
city: Gresham
country: United States
facility: Cyn3rgy Research
state: Oregon
city: Philadelphia
country: United States
facility: The Children's Hospital of Philadelphia
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Children's Hospital of Pittsburgh
state: Pennsylvania
city: Morgantown
country: United States
facility: WVU Medicine Pediatric and Adolescent Group Practice
state: West Virginia
city: Madison
country: United States
facility: American Family Children's Hospital
state: Wisconsin
Study officials:
affiliation: University of Pittsburgh
name: Nader Shaikh, MPH, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Wisconsin, American Family Children's Hospital
name: Ellen R Wald, MD
role: PRINCIPAL_INVESTIGATOR
References: