Sinus Infection, Acute Sinusitis
Conditions
Keywords
sinusitis, antibiotics, intranasal corticosteroids, saline nasal irrigation, comparative effectiveness
Brief summary
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.
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.
Interventions
Amoxicillin/clavulanate, oral, 875mg/125mg twice daily for 7 days
DRUGPlacebo
Placebo for amoxicillin/clavulanate, oral, twice daily for 7 days
Budesonide nasal spray, 32 mcg per spray, 2 sprays per nostril, once per day
Sponsors
Daniel Merenstein
Patient-Centered Outcomes Research Institute
Medstar Health Research Institute
University of Washington
Virginia Commonwealth University
University of California, Los Angeles
University of Wisconsin, Madison
Penn State College of Medicine
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Symptom Improvement | Change from Day 1 to Day 3 in Phase 2; differences in longitudinal trends across groups during Phase 2 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent improved beyond minimal clinically important difference | Phase 1: Baseline to Day 9; Phase 2: Day 1 to Day 3 | 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. |
| Patient non-randomization rate | Phase 1: baseline to Day 9 | 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. |
| Supportive care | Phase 1: Baseline to Day 9; Phase 1: Days 1, 3, 5, 7, 10, 14 | Types and frequency of supportive care used. |
| Work Productivity and Activity Impairment Questionnaire | Phase 1: Baseline, Day 9 day; Phase 2: Days 1, 7, and 14 | 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%). |
| Global Rating of Improvement as Quality of Life | Phase 1: Baseline, Day 9; Phase 2: Days 1, 7, and 14 | 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). |
| Adverse events | Phase 1: daily; Phase 2: daily | 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. |
| Adherence | Phase 2: Days 1-7 | 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. |
| Symptomatic care | Phase 1: daily; Phase 2: daily | Use patterns of over-the-counter medicines or supplements. |
| Prevalence of double-sickening | Direct randomization to Phase 2 | Worsening of symptoms after an initial improvement. |
Countries
United States
Contacts
CONTACTLead Project Coordinator
PRINCIPAL_INVESTIGATORDan Merenstein, MD
Georgetown University
Outcome results
None listed