Nasal Steroids, Irrigation, Oral Antibiotics, and Subgroup Targeting for Effective Management of Sinusitis

Study Overview
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Brief Summary
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Sinus infections are sometimes treated with antibiotics or nasal sprays, while some patients get better on their own. Some patients may wait a few days or use common over-the-counter remedies to see if their symptoms improve without further treatment. The overall goal of this clinical trial to see which patients with sinus infections are more likely to respond to different treatments, and which improve with supportive care alone.

Detailed Description
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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. Most acute sinus infections seen in outpatient setting are caused by viral infection, but antibiotics are prescribed in over 70% of these visits. The overarching goal is to improve outcomes for patients with ARS by understanding which subgroups 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 practice-based research networks within six geographical areas. Enrolled adults ages 18-65 years presenting to a clinician with symptoms consistent with ARS for less than 10 days will begin with a pre-randomization period with options for supportive care. Patients who reached more than 9 days of symptoms at the time of enrollment or during the waiting period will be randomly assigned to one of the four treatment arms. In preparation for the full-scale trial, a smaller feasibility study of the protocol will be piloted in a subset of clinics within the same research networks.

Official Title
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Nasal Steroids, Irrigation, Oral Antibiotics, and Subgroup Targeting for Effective Management of Sinusitis

Conditions
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Sinus Infection, Acute Sinusitis

Intervention / Treatment
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* Drug: Amoxicillin/clavulanate
* Drug: Placebo antibiotic
* Drug: Budesonide nasal spray
* Other: C-reactive protein
* Other: Mid-turbinate swab (optional)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ○ 18-65 years old; AND experiencing ongoing symptoms or signs that suggest an acute sinus infection lasting for 1-21 days, without any signs clinical improvement Exclusion Criteria: allergy or intolerance to penicillin received systemic antibiotic therapy in the past 4 weeks prior sinus surgery 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 unable to read, speak or understand English or Spanish hospitalization in past 5 days unable or unwilling to provide informed consent or comply with study protocol requirements fever >39°C or 102°F; OR taking intranasal corticosteroids (INCS) regularly in the past two weeks

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: antibiotic<br>amoxicillin/clavulanate | Drug: Amoxicillin/clavulanate<br>* Amoxicillin/clavulanate, oral, 875mg/125mg twice daily for 7 days<br>* Other names: Augmentin;Other: C-reactive protein<br>* Measurement of C-reactive protein level in capillary blood<br>* Other names: CRP;Other: Mid-turbinate swab (optional)<br>* Optional collection of mid-turbinate nasal swab sample<br>* Other names: Mid-nasal swab;|
| Placebo Comparator: placebo antibiotic<br>placebo antibiotic | Drug: Placebo antibiotic<br>* Placebo antibiotic, oral, twice daily for 7 days<br>* Other names: Control;Other: C-reactive protein<br>* Measurement of C-reactive protein level in capillary blood<br>* Other names: CRP;Other: Mid-turbinate swab (optional)<br>* Optional collection of mid-turbinate nasal swab sample<br>* Other names: Mid-nasal swab;|
| Active Comparator: antibiotic plus intranasal corticosteroid<br>amoxicillin/clavulanate plus budesonide | Drug: Amoxicillin/clavulanate<br>* Amoxicillin/clavulanate, oral, 875mg/125mg twice daily for 7 days<br>* Other names: Augmentin;Drug: Budesonide nasal spray<br>* Budesonide nasal spray, 32 mcg per spray, 2 sprays per nostril, once per day<br>* Other names: Rhinocort;Other: C-reactive protein<br>* Measurement of C-reactive protein level in capillary blood<br>* Other names: CRP;Other: Mid-turbinate swab (optional)<br>* Optional collection of mid-turbinate nasal swab sample<br>* Other names: Mid-nasal swab;|
| Other: placebo antibiotic plus intranasal corticosteroid<br>placebo antibiotic plus budesonide | Drug: Placebo antibiotic<br>* Placebo antibiotic, oral, twice daily for 7 days<br>* Other names: Control;Drug: Budesonide nasal spray<br>* Budesonide nasal spray, 32 mcg per spray, 2 sprays per nostril, once per day<br>* Other names: Rhinocort;Other: C-reactive protein<br>* Measurement of C-reactive protein level in capillary blood<br>* Other names: CRP;Other: Mid-turbinate swab (optional)<br>* Optional collection of mid-turbinate nasal swab sample<br>* Other names: Mid-nasal swab;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improvement of symptoms | 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. Scores will be measured at baseline and 3 days post-randomization. | Baseline and 3 days post-randomization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improvement of symptoms | 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. Scores will be measured at daily from baseline until 14 days post-randomization. | Baseline to 14 days post-randomization | 
| Work Productivity and Activity Impairment Questionnaire | The Work Productivity and Activity Impairment Questionnaire: Specific Health Problem (WPAI: SHP) 2.0 is a 6-question self-reported questionnaire on the effects of sinus symptoms on the amount of absenteeism, presenteeism, work impairment, and daily activity impairment. WPAI will be assessed at baseline, 9 days of symptoms is reached, and 1, 7, and 14 days post-randomization. | Baseline, 9 days of symptoms, and 1, 7, and 14 days post-randomization | 
| Global Rating of Improvement | 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). Scores will be measured at baseline, when 9 days of symptoms is reached, and 3, 7, and 14 days post-randomization. | Baseline, 9 days of symptoms, and 3, 7, and 14 days post-randomization | 
| Symptomatic care | Number of patients reporting use of over-the-counter medicines or supplements during the pre- and post-randomization study periods. | Baseline to 14 days post-randomization | 
| Adverse events | Number of adverse events reported during a follow-up or on the diary during the the pre- and post-randomization study periods. Events are graded form 1-5 using the NCI Common Terminology Criteria for Adverse Events. | Baseline to 14 days post-randomization | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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sinusitis, antibiotics, intranasal corticosteroids, saline nasal irrigation, comparative effectiveness