A Phase 4 interventional study of amoxicillin/clavulanate potassium and Placebo in Sinus Infection and Acute Sinusitis, sponsored by Daniel Merenstein. Recruiting at 7 sites in United States. Open to participants aged 18 Years to 75 Years. Per ClinicalTrials.gov, last updated 2026-03-03.
Sponsored by Daniel Merenstein · Phase 4, Interventional, and Treatment
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.
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.
256 studies on the registry are indexed under Sinusitis; 23 are open to participants now.
This study's planned enrollment of 3,720 is above the median of 60 across 196 interventional studies indexed under Sinusitis.
Browse Sinusitis studies →This is the only study on the registry with Daniel Merenstein as lead sponsor.
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Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
amoxicillin/clavulanate
Drug: amoxicillin/clavulanate potassium
placebo antibiotic (for amoxicillin/clavulanate)
Drug: Placebo
amoxicillin/clavulanate plus budesonide
Drug: amoxicillin/clavulanate potassium · Drug: Budesonide nasal spray
placebo antibiotic plus budesonide
Drug: Placebo · Drug: Budesonide nasal spray
Drug pages: Amoxicillin · Clavulanic Acid
Amoxicillin/clavulanate, oral, 875mg/125mg twice daily for 7 days
Also known as: Augmentin
Placebo for amoxicillin/clavulanate, oral, twice daily for 7 days
Also known as: Inactive, Control
Budesonide nasal spray, 32 mcg per spray, 2 sprays per nostril, once per day
Also known as: Rhinocort
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.
Time frame: Change from Day 1 to Day 3 in Phase 2; differences in longitudinal trends across groups during Phase 2
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.
Time frame: 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.
Time frame: Phase 1: baseline to Day 9
Supportive care
Types and frequency of supportive care used.
Time frame: 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%).
Time frame: 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).
Time frame: Phase 1: Baseline, Day 9; Phase 2: Days 1, 7, and 14
Symptomatic care
Use patterns of over-the-counter medicines or supplements.
Time frame: 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.
Time frame: 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.
Time frame: Phase 2: Days 1-7
Prevalence of double-sickening
Worsening of symptoms after an initial improvement.
Time frame: Direct randomization to Phase 2
Saline nasal irrigation - Concentration
Number who used 0.9 or 2% saline concentration
Time frame: Phase 1: daily; Phase 2; daily
Saline nasal irrigation - Frequency
Number who used SNI 1, 2 or 3 times per day
Time frame: Phase 1: daily; Phase 2; daily
Saline nasal irrigation - Timing
Number who used SNI before 12 pm or after 12 pm
Time frame: Phase 1: daily; Phase 2; daily
C-reactive protein (CRP)
Measurement of C-reactive protein (CRP) level as a predictor of bacterial infection, of not improving in Phase 1 and proceeding to Phase 2, and of poorer outcomes in non-antibiotic groups
Time frame: Phase 1 and Phase 2
Clinician's Estimation of the Likelihood of Bacterial Infection and/or Benefit From Antibiotics
Number of clinicians who responded low, intermediate, or high probability
Time frame: Enrollment day
Seasonal/Geographical Fluctuations in Symptom Severity
Difference in baseline mSNOT-16s score across sites and seasons
Time frame: Enrollment day
Change in mSNOT-16 scores from symptom start day to 14 days post-randomization
Longitudinal differences between daily mSNOT-16 scores from symptom start day, baseline and and visit days: Day 1-9 before randomization to Days 1-14 post-randomization. A decrease in mSNOT-16 score would indicate an improvement in symptoms.
Time frame: Symptom start day to 14 days post-randomization
Started Nov 2023 (actual). Primary completion is estimated for Oct 2028, 59 months after the start.
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Studies of the drugs tested here: Amoxicillin · Clavulanic Acid · Budesonide