Comparing nasal steroid spray, saline rinses, and antibiotics for adults with acute sinus infections

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

Phase 4 Interventional Georgetown University · NCT06076304

This test will see if antibiotics, a budesonide nasal spray, saline nasal irrigation, or combinations work best for adults 18–75 with acute sinus infections and which patients truly need antibiotics.

Quick facts

PhasePhase 4
Study typeInterventional
Enrollment3720 (estimated)
Ages18 Years to 75 Years
SexAll
SponsorGeorgetown University Academic / other
Locations7 sites (Los Angeles, California and 6 other locations)
Trial IDNCT06076304 on ClinicalTrials.gov

What this trial studies

This is a large, pragmatic, randomized controlled trial enrolling adults 18–75 who present to primary or urgent care with symptoms of acute rhinosinusitis. Participants will be randomized to receive oral amoxicillin/clavulanate versus placebo and to receive budesonide nasal spray versus not, with supportive measures such as saline irrigation also used per protocol. The study includes a pre-randomization waiting period (9+ days) for some participants and uses subgroup analyses (for example, elevated CRP, double-sickening, or purulence on exam) to identify who benefits most from antibiotics. Sites are spread across multiple geographic regions and include academic and health system partners.

Who should consider this trial

Good fit: Adults aged 18–75 with 1–21 days of persistent sinus symptoms without improvement or with 'double-sickening' after a viral URI, who have not recently taken systemic antibiotics and are not allergic to penicillin, are ideal candidates.

Not a fit: People with a penicillin allergy, recent systemic antibiotic use, prior sinus surgery that changes anatomy, complicated sinus infections, or chronic sinus disease may be ineligible or unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, the trial could reduce unnecessary antibiotic use and help clinicians match antibiotics, nasal steroids, or supportive care to the patients most likely to benefit.

How similar studies have performed: Prior research shows most ARS patients do not benefit from antibiotics but that subgroups with elevated CRP, double-sickening, or purulence are more likely to respond, so subgroup-targeted treatment is supported by evidence but not definitively proven in large pragmatic RCTs.

Eligibility criteria

Show full inclusion / exclusion criteria
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

Where this trial is running

Los Angeles, California and 6 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
Conditions Sinus InfectionAcute Sinusitissinusitisantibioticsintranasal corticosteroidssaline nasal irrigationcomparative effectiveness
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.