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

Overview

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

• Drug amoxicillin/clavulanate potassium
  Amoxicillin/clavulanate, oral, 875mg/125mg twice daily for 7 days
• Drug Placebo
  Placebo for amoxicillin/clavulanate, oral, twice daily for 7 days
• Drug Budesonide nasal spray
  Budesonide nasal spray, 32 mcg per spray, 2 sprays per nostril, once per day

Primary outcome measures

• Symptom Improvement [Time frame: Change from Day 1 to Day 3 in Phase 2; differences in longitudinal trends across groups during Phase 2]

Secondary outcome measures (9)

• Percent improved beyond minimal clinically important difference [Time frame: Phase 1: Baseline to Day 9; Phase 2: Day 1 to Day 3]
• Patient non-randomization rate [Time frame: Phase 1: baseline to Day 9]
• Supportive care [Time frame: Phase 1: Baseline to Day 9; Phase 1: Days 1, 3, 5, 7, 10, 14]
• Work Productivity and Activity Impairment Questionnaire [Time frame: Phase 1: Baseline, Day 9 day; Phase 2: Days 1, 7, and 14]
• Global Rating of Improvement as Quality of Life [Time frame: Phase 1: Baseline, Day 9; Phase 2: Days 1, 7, and 14]
• Symptomatic care [Time frame: Phase 1: daily; Phase 2: daily]
• Adverse events [Time frame: Phase 1: daily; Phase 2: daily]
• Adherence [Time frame: Phase 2: Days 1-7]
• Prevalence of double-sickening [Time frame: Direct randomization to Phase 2]

Eligibility criteria

Inclusion criteria

• 18-75 years old; AND are experiencing either:
• "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
• 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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Factorial

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

United States · 7 centers

• University of California, Los Angeles — Los Angeles
• Georgetown University Medical Center — Washington D.C.
• MedStar Health Research Institute — Hyattsville
• Penn State College of Medicine — Hershey
• Virginia Commonwealth University — Richmond
• University of Washington — Seattle
• University of Wisconsin-Madison — Madison

Identifiers

NCT: NCT06076304 · PLACER-2021C3-24476 · 23-02-622

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗