Comparative Effectiveness of Available Treatments for Sinus and Ear Infections in Children (Acute Sinusitis) (MEASURE)

This study is being conducted at multiple hospitals and clinics to better understand whether antibiotics truly help children feel better when they have a sinus infection (acute sinusitis). Children in the study are randomly assigned (like flipping a coin) to receive either amoxicillin, amoxicillin-clavulanate, or a placebo (a look-alike medicine with no active antibiotic). Neither families nor study staff know which treatment the child is receiving during the study. The main goal is to compare how severe children's symptoms are each day while on these treatments. Parents or caregivers will report symptoms daily using a simple electronic diary. The study will also examine whether factors such as the severity of the child's illness or signs of allergies affect how well antibiotics work. The results will help guide better treatment decisions for children with sinus infections.

Study Overview

• Status: Not yet recruiting
• Conditions: Sinusitis; ACUTE SINUSITIS
• Intervention / Treatment: Drug: Amoxicillin Placebo; Drug: Amoxicillin; Drug: Amoxi Clavulanate; Drug: Amoxicillin-Clavulanate Placebo

Detailed Description

This is a multi-center, randomized, double-blind, placebo-controlled study designed to better understand whether the choice of antibiotic affects symptom burden in children with acute sinusitis (AS). Children enrolled in the study are randomly assigned to receive amoxicillin, amoxicillin-clavulanate, or a matching placebo. Neither the families nor the study team know which treatment a child is receiving during the study period. The primary objective is to compare average daily symptom severity across treatment groups using validated caregiver-reported symptom scales collected through daily electronic diaries. Analyses will assess whether symptoms suggestive of allergy (sneezing or itchy eyes) or more severe nasal findings (such as marked congestion or perinasal crusting) influence treatment response. The goal is to provide rigorous, comparative evidence on antibiotic use in this common pediatric infection to support more informed clinical decision-making and responsible antimicrobial prescribing. The study will also examine whether factors such as the severity of the child's illness and signs of allergies affect how well antibiotics work. The results will help guide better treatment decisions for children with sinus infections

• Study Type: Interventional
• Enrollment (Estimated): 1100
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Jane Luce, MPH; Phone Number: 412-383-7853; Email: lucej2@upmc.edu

Study Locations

• United States
  • Colorado
    • Denver, Colorado, United States, 80204
      • University of Colorado, Denver
      • Contact: Sean O'Leary, MD; Phone Number: 303-724-1582; Email: sean.oleary@cuanschutz.edu
  • North Carolina
    • Durham, North Carolina, United States, 27705
      • Duke University Hospital
      • Contact: Charles Wood, MD; Phone Number: 919-620-4772; Email: charles.wood@duke.edu
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Children's Hospital
      • Contact: Bill Brinkman, MD; Phone Number: 513-636-2576; Email: bill.brinkman@cchmc.org
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • UPMC Children's Hospital of Pittsburgh
      • Contact: Nader Shaikh, MD; Phone Number: 412-692-8111; Email: Nader.Shaikh@chp.edu
  • Washington
    • Seattle, Washington, United States, 98105
      • Seattle Children's Hospital
      • Contact: Douglas Opel, MD; Phone Number: 206-987-6894; Email: douglas.opel@seattlechildrens.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age 2 years to <12 years.
• Clinical diagnosis of AS.

Exclusion Criteria:

• Known allergy or other contraindication to oral amoxicillin or clavulanate
• Prior use of systemic antibiotics in the last 7 days
• History of renal impairment
• History of hepatic impairment
• Phenylketonuria or allergy to aspartame
• History of craniofacial abnormalities
• Concurrent bacterial infection requiring systemic antibiotic therapy (e.g., pneumonia, streptococcal pharyngitis)
• Ill appearance, systemic toxicity, or immunodeficiency
• Incomplete pneumococcal vaccination, defined as receipt of fewer than three doses of a pneumococcal conjugate vaccine
• Parent or caregiver unable to complete study surveys in English or Spanish
• Previous randomization into either MEASURE trial within the last 6 months
• Periorbital redness and/or swelling, proptosis, or swelling of the forehead
• Individuals who qualify for both the AS and AOM trials (to avoid dual enrollment) will be excluded from the AS trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Amoxicillin; Participants randomized to this arm will receive oral amoxicillin for the treatment of acute sinusitis (AS). Caregivers will complete daily electronic symptom diaries throughout the treatment period.	Drug: Amoxicillin; Amoxicillin administered orally at protocol-specified, weight-based dosing consistent with standard pediatric treatment guidelines for AS, for the defined treatment duration.
Active Comparator: Amoxicillin-Clavulanate; Participants randomized to this arm will receive oral amoxicillin-clavulanate for the treatment of AS. Caregivers will complete daily electronic symptom diaries throughout the treatment period.	Drug: Amoxi Clavulanate; Amoxicillin-clavulanate administered orally at protocol-specified, weight-based dosing consistent with standard pediatric treatment guidelines for AOM or AS, for the defined treatment duration.
Placebo Comparator: Amoxicillin Placebo; Participants randomized to this arm will receive a matching oral placebo for the treatment of AS. Caregivers will complete daily electronic symptom diaries throughout the treatment period.	Drug: Amoxicillin Placebo; Matching placebo administered orally according to the same dosing schedule and treatment duration as the active comparator arms
Placebo Comparator: Amoxicillin-Clavulanate Placebo; Participants randomized to this arm will receive a matching oral placebo for the treatment of AS. Caregivers will complete daily electronic symptom diaries throughout the treatment period.	Drug: Amoxicillin-Clavulanate Placebo; Matching placebo administered orally according to the same dosing schedule and treatment duration as the active comparator arms.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Average Daily Symptom Burden	Symptom burden measured daily using the Pediatric Rhinosinusitis Symptom Scale (PRSS Version 2.0). PRSS scores range from 0 to 40, with higher scores indicating worse symptoms. Daily scores are averaged over Days 1-10	Days 1-10

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety Outcome: Diarrhea	Occurrence of diarrhea, defined as at least 3 watery stools in one day or at least 2 watery stools per day on two consecutive days.	Randomization through Day 10
Recurrence of Acute Sinusitis or Acute Otitis Media	Occurrence of one or more new episodes of clinically diagnosed acute sinusitis or acute otitis media following resolution of the index episode.	Days 11-90

Collaborators and Investigators

• Sponsor: Nader Shaikh
• Collaborators: Patient-Centered Outcomes Research Institute
• Investigators: Principal Investigator: Nader Shaikh, MD, University of Pittsburgh

Publications and helpful links

General Publications

• Varni JW, Sherman SA, Burwinkle TM, Dickinson PE, Dixon P. The PedsQL Family Impact Module: preliminary reliability and validity. Health Qual Life Outcomes. 2004 Sep 27;2:55. doi: 10.1186/1477-7525-2-55.
• Varni JW, Burwinkle TM, Seid M, Skarr D. The PedsQL 4.0 as a pediatric population health measure: feasibility, reliability, and validity. Ambul Pediatr. 2003 Nov-Dec;3(6):329-41. doi: 10.1367/1539-4409(2003)0032.0.co;2.
• Varni JW, Limbers CA, Neighbors K, Schulz K, Lieu JE, Heffer RW, Tuzinkiewicz K, Mangione-Smith R, Zimmerman JJ, Alonso EM. The PedsQL Infant Scales: feasibility, internal consistency reliability, and validity in healthy and ill infants. Qual Life Res. 2011 Feb;20(1):45-55. doi: 10.1007/s11136-010-9730-5. Epub 2010 Aug 22.
• Wald ER, Applegate KE, Bordley C, Darrow DH, Glode MP, Marcy SM, Nelson CE, Rosenfeld RM, Shaikh N, Smith MJ, Williams PV, Weinberg ST; American Academy of Pediatrics. Clinical practice guideline for the diagnosis and management of acute bacterial sinusitis in children aged 1 to 18 years. Pediatrics. 2013 Jul;132(1):e262-80. doi: 10.1542/peds.2013-1071.
• 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.
• Shaikh N, Wald ER, Jeong JH, Kurs-Lasky M, Nash D, Pichichero ME, Kearney DH, Haralam MA, Bowen A, Flom LL, Hoberman A. Development and Modification of an Outcome Measure to Follow Symptoms of Children with Sinusitis. J Pediatr. 2019 Apr;207:103-108.e1. doi: 10.1016/j.jpeds.2018.11.016. Epub 2018 Dec 10.

Study record dates

Study Major Dates

• Study Start (Estimated): October 1, 2026
• Primary Completion (Estimated): December 18, 2031
• Study Completion (Estimated): March 17, 2032

Study Registration Dates

• First Submitted: July 23, 2026
• First Submitted That Met QC Criteria: July 23, 2026
• First Posted (Actual): July 29, 2026

Study Record Updates

• Last Update Posted (Actual): July 29, 2026
• Last Update Submitted That Met QC Criteria: July 23, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: Sinusitis; Pediatric Sinusitis
• Additional Relevant MeSH Terms: Respiratory Tract Infections; Infections; Respiratory Tract Diseases; Nose Diseases; Otorhinolaryngologic Diseases; Paranasal Sinus Diseases; Sinusitis; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pharmaceutical Preparations; Amides; Drug Combinations; Penicillin G; beta-Lactams; Lactams; Clavulanic Acid; Clavulanic Acids; Ampicillin; Penicillins; Amoxicillin; Amoxicillin-Potassium Clavulanate Combination
• Other Study ID Numbers: STUDY26010103 (AS); PLACER-2024C3-42497 (Other Grant/Funding Number: PCORI)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual participant data (IPD) underlying the results reported in publications and the final study report, including relevant data dictionaries and metadata necessary to interpret the data, will be shared in accordance with PCORI's Policy for Data Management and Data Sharing. The shared data set will include the final cleaned and locked analyzable data set used for primary and secondary analyses reported from the study. Data will be de-identified in accordance with applicable federal and institutional privacy requirements, including the HIPAA Privacy Rule. Supporting documentation necessary to reproduce study findings and facilitate secondary analyses will also be made available.
• IPD Sharing Time Frame: De-identified IPD and supporting documentation will become available after publication of the primary study results and completion of PCORI's peer review and public release process, and no later than 12 months following publication of the primary results. Data and supporting documentation will remain available for at least seven years following study completion, consistent with PCORI policy requirements.
• IPD Sharing Access Criteria: Access to de-identified IPD and supporting documentation may be provided to qualified researchers for scientifically sound secondary research purposes, consistent with participant informed consent, institutional review board (IRB) requirements, and applicable laws and regulations. Requests may require submission of a research proposal, statistical analysis plan, and execution of a data use agreement. Data will be shared through a secure institutional or repository-based mechanism determined by the study team and sponsoring institution. Access decisions will be reviewed by the study investigators and/or designated data access committee in accordance with institutional and PCORI data sharing policies.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No