Efficacy of Antibiotics in Children With Acute Sinusitis: Which Subgroups Benefit?

NCT ID: NCT02554383

Last Updated: 2023-06-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 515 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-02-29
• Study Completion Date: 2023-03-09

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.

Conditions

Sinusitis; Respiratory Tract Infections

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Treatment A

Amoxicillin-clavulanate (90/6.4 mg/kg/d in 2 divided dosed for 10 days)

Group Type: ACTIVE_COMPARATOR

Amoxicillin-clavulanate

Intervention Type: DRUG

Amoxicillin-clavulanate (90/6.4 mg/kg/d in 2 divided dosed for 10 days)

Treatment B

Placebo made to match the study antibiotic will be taken bid orally for 10 days

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

placebo made to match the study antibiotic given twice a day orally for 10 days

Interventions

Amoxicillin-clavulanate

Amoxicillin-clavulanate (90/6.4 mg/kg/d in 2 divided dosed for 10 days)

Intervention Type: DRUG

Placebo

placebo made to match the study antibiotic given twice a day orally for 10 days

Intervention Type: DRUG

Other Intervention Names

Augmentin-Extra strength

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

• Minimum Eligible Age: 2 Years
• Maximum Eligible Age: 11 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: collaborator

Nader Shaikh

OTHER

Sponsor Role: lead

Responsible Party

Nader Shaikh

Associate Professor of Pediatrics, University of Pittsburgh School of Medicine

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Nader Shaikh, MPH, MD

Role: PRINCIPAL_INVESTIGATOR

University of Pittsburgh

Ellen R Wald, MD

Role: PRINCIPAL_INVESTIGATOR

University of Wisconsin, American Family Children's Hospital

Locations

Kentucky Pediatric/Adult Research

Bardstown, Kentucky, United States

Cyn3rgy Research

Gresham, Oregon, United States

The Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

UPMC Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, United States

WVU Medicine Pediatric and Adolescent Group Practice

Morgantown, West Virginia, United States

American Family Children's Hospital

Madison, Wisconsin, United States

Countries

United States

References

Shaikh N, Hoberman A, Shope TR, Jeong JH, Kurs-Lasky M, Martin JM, Bhatnagar S, Muniz GB, Block SL, Andrasko M, Lee MC, Rajakumar K, Wald ER. Identifying Children Likely to Benefit From Antibiotics for Acute Sinusitis: A Randomized Clinical Trial. JAMA. 2023 Jul 25;330(4):349-358. doi: 10.1001/jama.2023.10854.

Reference Type: DERIVED

PMID: 37490085 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

U01AI118506

Identifier Type: NIH

Identifier Source: secondary_id

View Link

STUDY20110386

Identifier Type: -

Identifier Source: org_study_id