Nasal Steroids, Irrigation, Oral Antibiotics, and Subgroup Targeting for Effective Management of Acute Sinusitis (NOSES)

Sinus infections (also called acute rhinosinusitis or ARS) affect about 15% of adults each year, and are one of the top reasons people receive antibiotics in outpatient settings. Since most sinus infections are caused by viruses, many patients who take antibiotics for this condition do not actually benefit. Even though this has decreased over recent years, 70% of people are still prescribed them after a visit for ARS. Our goal is to better understand which patients truly benefit from antibiotics and which other treatment options can help people with sinus infections.

Study Overview

• Status: Recruiting
• Conditions: Sinus Infection; Acute Sinusitis
• Intervention / Treatment: Drug: Budesonide nasal spray; Drug: Placebo; Drug: amoxicillin/clavulanate potassium

Detailed Description

One in seven adults are diagnosed with acute sinus infections (also known as rhinosinusitis or ARS) every year in the United States, for an annual total of 30 million office visits. The majority of physician-diagnosed, acute sinus infections in outpatient setting are caused by viral infection, but antibiotics are prescribed in over 70% of these visits--without significant benefits to patients compared to placebo. Most ARS cases resolve without antibiotics; however, some patients do benefit from antibiotics. Previous research suggests that individuals with an elevated c-reactive protein level, double-sickening (worsening of sinus symptoms after initial improvement), or evidence of purulence on clinical examination, are more likely to respond to antibiotic treatment. The overarching goal of this study is to improve outcomes for patients with ARS by better understanding which groups of patients are most likely to benefit from antibiotics, supportive care, watchful waiting, intranasal corticosteroids (INCS), or a combination of treatments.

To assess the comparative effectiveness of the treatments, a large, pragmatic, randomized controlled trial, will be conducted in primary and urgent care clinics within six geographical areas. This trial will enroll adults 18-75 years of age who present to a clinician with symptoms consistent with ARS. Patients participating in this study will enter one of two phases. Phase 1 is a pre-randomization, waiting period of 9 or more days, with options for supportive care. Participants who do not improve by the end of 9 days, had symptoms for more than 9 days at enrollment, or have experienced double-sickening, will proceed to Phase 2 and be randomly assigned to one of the four intervention arms. Sixty percent of the 3,720 enrolled are estimated to participate in Phase 2, resulting in a sample size of 1,860 randomized after attrition. During Phase 1 (up to 9 days) and Phase 2 (14 days), all participants complete a two-minute daily diary and periodic follow-ups about their symptoms.

• Study Type: Interventional
• Enrollment (Estimated): 3720
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Lead Project Coordinator; Phone Number: 202-687-6454; Email: researchfammed@georgetown.edu

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90095
      • Recruiting
      • University of California, Los Angeles
      • Principal Investigator: Derjung Mimi Tarn, MD, PhD
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20007
      • Recruiting
      • Georgetown University Medical Center
      • Principal Investigator: Daniel Merenstein, MD
  • Maryland
    • Hyattsville, Maryland, United States, 20782
      • Not yet recruiting
      • Medstar Health Research Institute
      • Principal Investigator: Nawar Shara, PhD
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Recruiting
      • Penn State College of Medicine
      • Principal Investigator: David Rabago, MD
  • Virginia
    • Richmond, Virginia, United States, 23219
      • Recruiting
      • Virginia Commonwealth University
      • Principal Investigator: Alexander Krist, MD, MPH
  • Washington
    • Seattle, Washington, United States, 98195
      • Recruiting
      • University of Washington
      • Principal Investigator: Sebastian Tong, MD, MPH
  • Wisconsin
    • Madison, Wisconsin, United States, 53705
      • Recruiting
      • University of Wisconsin-Madison
      • Principal Investigator: Bruce Barrett, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. 18-75 years old; AND are experiencing either:
2. "persistent" symptoms or signs compatible with ARS or sinus infection lasting for 1-21 days without any evidence of clinical improvement (Symptoms include facial pain or pressure, facial congestion or fullness, nasal obstruction, nasal discharge, no or reduced sense of smell, fever ≤39°C or 102°F, headache, bad smelling breath, fatigue, ear pain or pressure, and dental pain); OR
3. onset with worsening symptoms or signs characterized by the new onset of fever, headache, or increase in nasal discharge following a typical viral upper respiratory infection (URI) that lasted 5-6 days and were initially improving (''double-sickening'').

Exclusion Criteria:

• allergy or intolerance to penicillin
• received systemic antibiotic therapy in the past 4 weeks
• prior sinus surgery (cosmetic surgery, such as rhinoplasty, septal deviation, etc. are not exclusionary)
• complications of sinusitis (facial edema (swelling), cellulitis), or orbital, meningeal or cerebral signs)
• health care clinician determined IV (intravenous) antibiotics or hospital admission are required
• pregnancy or breastfeeding
• presence of a comorbidity or medication that may impair a patient's immune response as determined by a health care clinician
• hospitalization in past 5 days
• unable or unwilling to provide informed consent or comply with study protocol requirements
• fever >39°C or 102°F today
• taking intranasal corticosteroids (INCS) regularly in the past two weeks and unwilling to stop its use while in the study; OR
• previously enrolled or participated in the feasibility phase or this stage of study

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: antibiotic; amoxicillin/clavulanate	Drug: amoxicillin/clavulanate potassium; Amoxicillin/clavulanate, oral, 875mg/125mg twice daily for 7 days; Other Names: Augmentin
Active Comparator: antibiotic plus intranasal corticosteroid; amoxicillin/clavulanate plus budesonide	Drug: Budesonide nasal spray; Budesonide nasal spray, 32 mcg per spray, 2 sprays per nostril, once per day; Other Names: Rhinocort; Drug: amoxicillin/clavulanate potassium; Amoxicillin/clavulanate, oral, 875mg/125mg twice daily for 7 days; Other Names: Augmentin
Other: placebo antibiotic plus intranasal corticosteroid; placebo antibiotic plus budesonide	Drug: Budesonide nasal spray; Budesonide nasal spray, 32 mcg per spray, 2 sprays per nostril, once per day; Other Names: Rhinocort; Drug: Placebo; Placebo for amoxicillin/clavulanate, oral, twice daily for 7 days; Other Names: Control; Inactive
Placebo Comparator: placebo antibiotic; placebo antibiotic (for amoxicillin/clavulanate)	Drug: Placebo; Placebo for amoxicillin/clavulanate, oral, twice daily for 7 days; Other Names: Control; Inactive

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Symptom Improvement	Improvement of symptoms will be assessed using the Modified Sino-Nasal Outcome Test (mSNOT-16), a disease-specific quality of life questionnaire. Sixteen sinus symptoms are self-assessed on a 0-3 point scale, with 0=No Problem, 1=Mild or Slight Problem, 2=Moderate Problem, 3=Severe Problem. The mean of the total score is used to assess symptom severity. Daily measures will be collected both in Phase 1 and Phase 2.	Change from Day 1 to Day 3 in Phase 2; differences in longitudinal trends across groups during Phase 2

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent improved beyond minimal clinically important difference	Percent of patients who improved more than 0.5; improvement of symptoms will be assessed using the Modified Sino-Nasal Outcome Test (mSNOT-16), a disease-specific quality of life questionnaire. Sixteen sinus symptoms are self-assessed on a 0-3 point scale, with 0=No Problem, 1=Mild or Slight Problem, 2=Moderate Problem, 3=Severe Problem.	Phase 1: Baseline to Day 9; Phase 2: Day 1 to Day 3
Patient non-randomization rate	Percentage of patients who were enrolled in Phase 1 but did not proceed to randomization because they reported their condition had improved. This is determined by the patient at the Day 9 assessment, by decreased mSNOT-16 scores from baseline, or no longer reports symptoms listed in the inclusion criteria.	Phase 1: baseline to Day 9
Supportive care	Types and frequency of supportive care used.	Phase 1: Baseline to Day 9; Phase 1: Days 1, 3, 5, 7, 10, 14
Work Productivity and Activity Impairment Questionnaire	Work and activity impairment due to acute sinusitis; the Work Productivity and Activity Impairment Questionnaire: Specific Health Problem 2.0 is a 6-question self-reported questionnaire on the effects of sinus symptoms on the amount of absenteeism (percent work time missed), presenteeism (percent impairment while working), overall work impairment, and daily activity impairment. Higher percentages indicate greater impairment and less productivity (scale 0-100%).	Phase 1: Baseline, Day 9 day; Phase 2: Days 1, 7, and 14
Global Rating of Improvement as Quality of Life	Self-assessment of current sinus symptoms at each follow-up interview using a 6-point categorical scale (1=no symptoms, 2=a lot better, 3=a little better, 4=the same, 5=a little worse, or 6=a lot worse).	Phase 1: Baseline, Day 9; Phase 2: Days 1, 7, and 14
Symptomatic care	Use patterns of over-the-counter medicines or supplements.	Phase 1: daily; Phase 2: daily
Adverse events	Adverse events reported during a follow-up or on the diary. Events are graded form 1-5 using the NCI Common Terminology Criteria for Adverse Events.	Phase 1: daily; Phase 2: daily
Adherence	Self-reported adherence to study pill and nasal spray are calculated by [number of doses taken]/[prescribed number of doses] x 100, over the 7-day intervention period.	Phase 2: Days 1-7
Prevalence of double-sickening	Worsening of symptoms after an initial improvement.	Direct randomization to Phase 2

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Saline nasal irrigation - Concentration	Number who used 0.9 or 2% saline concentration	Phase 1: daily; Phase 2; daily
Saline nasal irrigation - Frequency	Number who used SNI 1, 2 or 3 times per day	Phase 1: daily; Phase 2; daily
Saline nasal irrigation - Timing	Number who used SNI before 12 pm or after 12 pm	Phase 1: daily; Phase 2; daily
C-reactive protein (CRP)	Measurement of C-reactive protein (CRP) level as a predictor of bacterial infection, of not improving in Phase 1 and proceeding to Phase 2, and of poorer outcomes in non-antibiotic groups	Phase 1 and Phase 2
Clinician's Estimation of the Likelihood of Bacterial Infection and/or Benefit From Antibiotics	Number of clinicians who responded low, intermediate, or high probability	Enrollment day
Seasonal/Geographical Fluctuations in Symptom Severity	Difference in baseline mSNOT-16s score across sites and seasons	Enrollment day
Change in mSNOT-16 scores from symptom start day to 14 days post-randomization	Longitudinal differences between daily mSNOT-16 scores from symptom start day, baseline and and visit days: Day 1-9 before randomization to Days 1-14 post-randomization. A decrease in mSNOT-16 score would indicate an improvement in symptoms.	Symptom start day to 14 days post-randomization

Collaborators and Investigators

• Sponsor: Daniel Merenstein
• Collaborators: Patient-Centered Outcomes Research Institute; University of California, Los Angeles; University of Wisconsin, Madison; University of Washington; Virginia Commonwealth University; Medstar Health Research Institute; Penn State College of Medicine
• Investigators: Principal Investigator: Dan Merenstein, MD, Georgetown University

Study record dates

Study Major Dates

• Study Start (Actual): November 21, 2023
• Primary Completion (Estimated): October 1, 2028
• Study Completion (Estimated): December 1, 2028

Study Registration Dates

• First Submitted: September 25, 2023
• First Submitted That Met QC Criteria: October 3, 2023
• First Posted (Actual): October 10, 2023

Study Record Updates

• Last Update Posted (Actual): March 3, 2026
• Last Update Submitted That Met QC Criteria: February 27, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: antibiotics; comparative effectiveness; sinusitis; intranasal corticosteroids; saline nasal irrigation
• 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; Polycyclic Compounds; Amides; Pregnanes; Steroids; Fused-Ring Compounds; Pregnenediones; Pregnenes; Drug Combinations; Penicillin G; beta-Lactams; Lactams; Clavulanic Acid; Clavulanic Acids; Ampicillin; Penicillins; Amoxicillin; Budesonide; Amoxicillin-Potassium Clavulanate Combination
• Other Study ID Numbers: PLACER-2021C3-24476; 23-02-622 (Other Identifier: IRB)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No