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

Daniel Merenstein

Status and phase: Active, not recruiting; Phase 4

Conditions: Acute Sinusitis; Sinus Infection

Treatments: Drug: Amoxicillin/Clavulanate Potassium 875 MG-125 MG Oral Tablet; Drug: Budesonide nasal spray; Other: C-reactive protein; Drug: Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT06076304

PLACER-2021C3-24476

23-02-622 (Other Identifier)

Details and patient eligibility

About

Sinus infections are sometimes treated with oral antibiotics or nasal steroid 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. Sometimes this is enough to help patients wait a few days to see if their infection clears up without needing to use antibiotics or nasal steroid sprays. The overall goal of this clinical trial to see which specific groups of patients benefit more from which intervention or combination of intervention, and which improve with supportive care alone.

Full 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. 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 primary and urgent care clinics within six geographical areas. Enrolled adults ages 18-75 years presenting to a clinician with symptoms consistent with ARS will enter the study in one of 2 phases, dependent on the number of days with symptoms. Phase 1 is a pre-randomization, waiting period of 9 or more days, with options for supportive care. Patients who qualify will enter Phase 2 and will be randomly assigned to one of the four arms. All groups will use approved or over-the counter drugs or spray, or a placebo (inactive or dummy pill). Patients will be in Phase 2 for approximately 14 days. All patients will complete a two-minute daily diary and periodic follow-ups about their symptoms.

Enrollment: 3,720 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Factorial Assignment

Masking: Quadruple Blind

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3,720 participants in 4 patient groups, including a placebo group

antibiotic

Active Comparator group

Description:

amoxicillin/clavulanate

Treatment:

Other: C-reactive protein

Drug: Amoxicillin/Clavulanate Potassium 875 MG-125 MG Oral Tablet

placebo antibiotic

Placebo Comparator group

Description:

placebo antibiotic, amoxicillin/clavulanate

Treatment:

Drug: Placebo

Other: C-reactive protein

antibiotic plus intranasal corticosteroid

Active Comparator group

Description:

amoxicillin/clavulanate plus budesonide

Treatment:

Other: C-reactive protein

Drug: Budesonide nasal spray

Drug: Amoxicillin/Clavulanate Potassium 875 MG-125 MG Oral Tablet

placebo antibiotic plus intranasal corticosteroid

Other group

Description:

placebo antibiotic plus budesonide

Treatment:

Drug: Placebo

Other: C-reactive protein

Drug: Budesonide nasal spray