Efficacy of Antibiotics in Children With Acute Sinusitis: Which Subgroups Benefit?
|Sinusitis Respiratory Tract Infections||Drug: Amoxicillin-clavulanate Drug: Placebo||Phase 3|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||Efficacy of Antibiotics in Children With Acute Sinusitis: Which Subgroups Benefit?|
- Symptom Severity [ Time Frame: From Day 1 after randomization until day 11 ]Treatment effect will be measured primarily using the validated Pediatric Rhinosinusitis Symptom Scale (PRSS) which will be administered every evening as an electronic diary.
- Treatment Failure [ Time Frame: From Day 1 after randomization to day 18 ]
- Worsening at any time-PRSS score increased by >20% from entry.
- No change by 48 hours-PRSS score decreased by <2 points from entry (Day 1) to Day 3.
- Failure to improve significantly by 72 hours-PRSS score decreased by <20% from entry (Day 1) to Day 4.
- Still symptomatic (PRSS score ≥50% of entry score) at the time of the end-of-study follow-up visit (Days 12 to 18).
- Number of Participants with Acute Otitis Media [ Time Frame: From Day 1 after randomization to day 11 ]Acute symptoms and a bulging tympanic membrane on Days 1 to 11.
- Number of Participants who received systemic antibiotics for any indication [ Time Frame: From Day 1 after randomization to day 11 ]Receipt of an antibiotic (other than the assigned study medication) on Days 1 to 11 for any indication.
- Adverse Events [ Time Frame: From Day 1 after randomization to Day 18 ]The proportions of children experiencing adverse events will be compared (protocol-defined diarrhea and Moderate or severe rash or other severe AE). Protocol-defined diarrhea will be defined as the occurrence of ≥3 watery stools in 1 day or 2 watery stools per day for 2 consecutive days, and will be tracked in the daily diary.
- Proportion Compliant with Study Product [ Time Frame: From Day 1 after randomization to Day 18 ]Compliance - In the daily diary, the investigators will ask participants to record whether they administered the doses of study product. Administration of ≥70% of the doses will be considered compliant.
- Costs of Care [ Time Frame: From Day 1 after randomization to Day 18 ]Direct medical costs and indirect medical costs will be obtained.
|Study Start Date:||February 2016|
|Estimated Study Completion Date:||September 2020|
|Estimated Primary Completion Date:||September 2020 (Final data collection date for primary outcome measure)|
Active Comparator: Treatment A
Amoxicillin-clavulanate (90/6.4 mg/kg/d in 2 divided dosed for 10 days)
Amoxicillin-clavulanate (90/6.4 mg/kg/d in 2 divided dosed for 10 days)
Other Name: Augmentin-Extra strength
Placebo Comparator: Treatment B
Placebo made to match the study antibiotic will be taken bid orally for 10 days
placebo made to match the study antibiotic given twice a day orally for 10 days
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT02554383
|Contact: Jennifer P Nagg, RN, MSfirstname.lastname@example.org|
|Contact: Rebecca Stallings, BAemail@example.com|
|United States, Kentucky|
|Kentucky Pediatric/Adult Research||Recruiting|
|Bardstown, Kentucky, United States, 40004|
|Contact: Marty Osbourn, RN CCRC 502-349-1569 firstname.lastname@example.org|
|United States, New York|
|Legacy [ediatrics||Not yet recruiting|
|Rochester, New York, United States, 14618|
|Contact: Janet Casey, MD email@example.com|
|United States, Pennsylvania|
|The Children's Hospital of Philadelphia||Active, not recruiting|
|Philadelphia, Pennsylvania, United States, 19104|
|Children's Hospital of UPMC||Recruiting|
|Pittsburgh, Pennsylvania, United States, 15224|
|Contact: Jennifer P Nagg, RN, MS 412-692-8586 firstname.lastname@example.org|
|Contact: Rebecca Stallings, BA 412-692-9638 email@example.com|
|United States, West Virginia|
|WVU Medicine Pediatric and Adolescent Group Practice||Not yet recruiting|
|Morgantown, West Virginia, United States, 26501|
|Contact: Michelle Shaffer, CCRP 304-893-1039 firstname.lastname@example.org|
|Principal Investigator: Timothy Lefeber, MD|
|United States, Wisconsin|
|American Family Children's Hospital||Recruiting|
|Madison, Wisconsin, United States, 53792|
|Contact: Jody Belling, RN, MSN 608-265-1894 email@example.com|
|Contact: Cherie E Schommer, BA 608-262-2631 firstname.lastname@example.org|
|Principal Investigator:||Nader Shaikh, MPH, MD||University of Pittsburgh|
|Principal Investigator:||Ellen R Wald, MD||University of Wisconsin, American Family Children's Hospital|