Sinus InfectionPhase 4NOSESNCT06076304
Nasal Steroids, Irrigation, Oral Antibiotics, and Subgroup Targeting for Effective Management of Acute Sinusitis
A Phase 4 study testing amoxicillin/clavulanate potassium and Budesonide nasal spray in people with Sinus Infection and Acute Sinusitis, run by Daniel Merenstein at 7 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Sinus Infection, Acute Sinusitis
- What is being tested?
- amoxicillin/clavulanate potassium and Budesonide nasal spray
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 3,720 participants
- Where
- 7 sitesUnited States
- Study dates
- 21 Nov 2023to Dec 2028
- Phase
- Phase 4
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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'').
Who cannot join
- 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
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- 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 locations and contacts
7 sites in 1 country. Contact the study team or a site near you to ask about taking part.
7 sites in 1 country
United States7 sites, 7 recruiting
- Recruiting
Penn State College of Medicine
Hershey, Pennsylvania, 17033
David Rabago, MD
- Not yet recruiting
MedStar Health Research Institute
Hyattsville, Maryland, 20782
Nawar Shara, PhD
- Recruiting
University of California, Los Angeles
Los Angeles, California, 90095
Derjung Mimi Tarn, MD, PhD
- Recruiting
University of Wisconsin-Madison
Madison, Wisconsin, 53705
Bruce Barrett, MD, PhD
- Recruiting
Virginia Commonwealth University
Richmond, Virginia, 23219
Alexander Krist, MD, MPH
- Recruiting
University of Washington
Seattle, Washington, 98195
Sebastian Tong, MD, MPH
- Recruiting
Georgetown University Medical Center
Washington D.C., District of Columbia, 20007
Daniel Merenstein, MD
About this study
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.
Read the 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.
- Conditions
- Sinus Infection, Acute Sinusitis
- Being tested
- amoxicillin/clavulanate potassium, Placebo, Budesonide nasal spray
- Keywords
- sinusitis, antibiotics, intranasal corticosteroids, saline nasal irrigation, comparative effectiveness
- Medical subject headings
- Sinusitis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
amoxicillin/clavulanate potassiumDrug
Also called Augmentin
Amoxicillin/clavulanate, oral, 875mg/125mg twice daily for 7 days
PlaceboDrug
Also called Inactive, Control
Placebo for amoxicillin/clavulanate, oral, twice daily for 7 days
Budesonide nasal sprayDrug
Also called Rhinocort
Budesonide nasal spray, 32 mcg per spray, 2 sprays per nostril, once per day
| Study group | Role | What they receive |
|---|---|---|
| antibiotic | Active comparator | amoxicillin/clavulanate Receives: Drug: amoxicillin/clavulanate potassium |
| placebo antibiotic | Placebo comparator | placebo antibiotic (for amoxicillin/clavulanate) Receives: Drug: Placebo |
| antibiotic plus intranasal corticosteroid | Active comparator | amoxicillin/clavulanate plus budesonide Receives: Drug: amoxicillin/clavulanate potassium; Drug: Budesonide nasal spray |
| placebo antibiotic plus intranasal corticosteroid | Other | placebo antibiotic plus budesonide Receives: Drug: Placebo; Drug: Budesonide nasal spray |
What is being measured
The primary outcome is the main question the study is designed to answer.
Symptom Improvement
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.
Measured: Change from Day 1 to Day 3 in Phase 2; differences in longitudinal trends across groups during Phase 2
Secondary outcomes (9)
Percent improved beyond minimal clinically important difference
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.
Measured: Phase 1: Baseline to Day 9; Phase 2: Day 1 to Day 3
Patient non-randomization rate
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.
Measured: Phase 1: baseline to Day 9
Supportive care
Types and frequency of supportive care used.
Measured: Phase 1: Baseline to Day 9; Phase 1: Days 1, 3, 5, 7, 10, 14
Work Productivity and Activity Impairment Questionnaire
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%).
Measured: Phase 1: Baseline, Day 9 day; Phase 2: Days 1, 7, and 14
Global Rating of Improvement as Quality of Life
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).
Measured: Phase 1: Baseline, Day 9; Phase 2: Days 1, 7, and 14
Symptomatic care
Use patterns of over-the-counter medicines or supplements.
Measured: Phase 1: daily; Phase 2: daily
Adverse events
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.
Measured: Phase 1: daily; Phase 2: daily
Adherence
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.
Measured: Phase 2: Days 1-7
Prevalence of double-sickening
Worsening of symptoms after an initial improvement.
Measured: Direct randomization to Phase 2
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Oct 2023
- Study start21 Nov 2023
- Primary completionOct 2028 (estimated)
- Study completionDec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Sinus InfectionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 3,720 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Daniel Merenstein
- Sponsor type
- University, hospital or other
- Collaborators
- 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
- Responsible party
- Sponsor-investigator, Daniel Merenstein, Georgetown University
- Investigators
- Dan Merenstein, MD, Principal investigator, Georgetown University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06076304
- Sponsor's protocol ID
- PLACER-2021C3-24476
- Other IDs
- 23-02-622
- Acronym
- NOSES
- Status last verified
- Feb 2026
- First submitted
- 25 Sep 2023
- Last updated
- 3 Mar 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No