Treatment of Acute Sinusitis With High-Dose vs. Standard-Dose Amoxicillin/Clavulanate

Study Overview
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Brief Summary
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Comparative-effectiveness study of the treatment of acute bacterial sinusitis with amoxicillin/clavulanate 875mg/125mg bid for 7 days with or without the addition of immediate-release amoxicillin 875 mg bid x 7 days. .

Detailed Description
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Double-blind comparative-effectiveness study of the treatment of acute bacterial sinusitis with standard dose of amoxicillin/clavulanate 875mg/125mg bid for 7 days, as recommended by the Infectious Disease Society of America, with or without the addition of immediate-release amoxicillin 875 mg bid x 7 days. The study aims are 1) to confirm, or not, our recent findings of more rapid improvement in overall symptoms with the additional amoxicillin, but also of more frequent diarrhea and vaginal yeast infections and 2) to assess, from the participants' point of view, the balance between improvement and adverse effects.

Official Title
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Treatment of Acute Sinusitis With High-Dose vs. Standard-Dose Amoxicillin/Clavulanate: A Confirmation Study

Conditions
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Sinusitis, Acute

Intervention / Treatment
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* Drug: Amoxicillin 875 mg
* Dietary Supplement: Placebo (lactase)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults 18 and older who are patients at the Albany Medical Center Internal Medicine and Pediatrics practice (study site). Clinical diagnosis of acute bacterial sinusitis in accordance with the guidelines of the Infectious Disease Society of America (fitting into one of 3 categories: persistent sinus symptoms for 10 days or more; severe sinus symptoms for 3 days or more; or worsening sinus symptoms after initial improvement (double sickening). Exclusion Criteria: Previous enrollment in the current study Allergy or intolerance to any penicillin or to amoxicillin/clavulanate Serious hypersensitivity reaction to any beta lactam Elevated risk of amoxicillin-resistant bacteria: a. amoxicillin, penicillin, or other beta-lactam within the past month; b. known to have had methicillin-resistant Staph aureus Chronic or recurrent sinus problems (defined as a) persistent symptoms of sinus congestion, not attributed to nasal allergies, for 8 weeks or more or b) 2 or more episodes of antibiotic-treated sinusitis in past 3 months Need to use high-dose amoxicillin/clavulanate or levofloxacin or to send to emergency department or to hospitalize because of a) signs of severe infection or b) immunocompromise Cognitive impairment, so unable to give reliable symptom ratings (even if a health proxy can give consent) Pregnant women and nursing mothers Drug warnings: a) taking allopurinol; b) current mononucleosis; c) chronic kidney disease stage 4 (estimated glomerular filtration rate <30); d) hepatic impairment (not including isolated transaminase elevated < 2 times upper limit of normal); e) history of antibiotic-associated colitis (C. difficile)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Ill adult patients coming to a primary care office will be diagnosed by the treating physicians with acute bacterial sinusitis in accordance with the guidelines of the Infectious Disease Society of America. If they do not meet exclusion criteria, they will be offered enrollment in the study. If they agree, they will be provided unlabeled study medication, either amoxicillin/clavulanate 875/125 + placebo pills bid x 7 days (standard dose) or amoxicillin/clavulanate 875/125 + amoxicillin immediate-release 875 (high dose). Outcomes will be assessed, by telephone or over the web (through Qualtrics), at 3 and 10 days after enrollment.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: High dose<br>Amoxicillin/clavulanate 875mg/125mg & amoxicillin 875 mg twice a day x 7 days | Drug: Amoxicillin 875 mg<br>* Doubling the dose of amoxicillin by adding amoxicillin 875 to each dose of the standard treatment of amoxicillin/clavulanate 875/125<br>* Other names: Amoxil;|
| Active Comparator: Standard dose<br>Amoxicillin/clavulanate 875 mg/125mg & placebo (lactase) twice a day x 7 days. | Dietary Supplement: Placebo (lactase)<br>* Placebo (in place of additional amoxicillin in experimental arm)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With a Global Rating of Improvement of 5 & 6 at the End of 3 Days of Treatment | Rating on a scale of 1=a lot worse, 2=a little worse, 3=the same, 4=a little better, 5=a lot better, 6=no symptoms, with a higher score indicating greater improvement. | At end of 3 days of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With a Global Rating of Improvement of 5 or 6 at End of 10 Days Since Enrollment | Rating of 5 (a lot better) or 6 (no symptoms) on Global Rating of Improvement scale, with range of 1 (a lot worse) to 6 (no symptoms), with a higher score indicating greater improvement | At end of 10 days since enrollment | 
| Change From Baseline in the Total Score on the Sinonasal Outcome Test-16 (SNOT-16) at the End of 3 Days of Treatment | The change between enrollment and the end of 3 days of treatment in the total score on the Sinonasal Outcome Test-16 (SNOT-16). The total SNOT-16 is the sum of the participant's ratings of 16 symptoms of illness on the scale of 0 (no problem) to 3 (severe problem), with a possible range of 0 to 48, with a higher sum indicating more troubling symptoms. A decrease in total score would indicate an improvement in symptoms. | At end of 3 days of treatment | 
| Change From Baseline in the Total Score on the Sinonasal Outcome Test-16 (SNOT-16) at the End of 10 Days Since Enrollment | The change between enrollment and the end of 10 days since enrollment in the total score on the Sinonasal Outcome Test-16 (SNOT-16). The total SNOT-16 is the sum of the participant's ratings of 16 symptoms of illness on the scale of 0 (no problem) to 3 (severe problem), with a possible range of 0 to 48, with a higher sum indicating more troubling symptoms. A decrease in total score would indicate an improvement in symptoms. | At end of 10 days since enrollment | 
| Balance of Benefits and Detriments | Assessment of balance between good effects and bad effects of antibiotic on scale of -3=bad effects much greater than good effects to +3=good effects much greater than bad effects | At end of 10 days since enrollment | 
| Number of Participants Answering Yes to Willingness to Take the Antibiotic Again in the Future | Response of yes at the end of 10 days since enrollment to the question whether the participant would take this antibiotic again, with possible answers of yes, no, or uncertain. | At end of 10 days since enrollment |