Clinical Trial of the Treatment of Acute Sinusitis With Standard-dose Versus High-dose Amoxicillin/Clavulanate

Study Overview
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Brief Summary
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The aim is to determine if high-dose amoxicillin/clavulanate is more effective than standard-dose amoxicillin/clavulanate in treating acute bacterial sinusitis in adults seen at a primary care office.

Detailed Description
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The aim was amended in February 2016--because of the unexpected unavailability of the original high-dose formulation of amoxicillin/clavulanate--to compare the effectiveness (versus standard dose) of extended-release (the original formulation) versus immediate-release amoxicillin/clavulanate.

Official Title
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Clinical Trial of the Treatment of Acute Sinusitis With Standard-dose Versus High-dose Amoxicillin/Clavulanate

Conditions
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Sinusitis

Intervention / Treatment
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* Drug: standard dose amoxicillin/clavulanate
* Drug: high dose amoxicillin/clavulanate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult 18 or over Meets definition of acute sinusitis by Infectious Disease Society of America (2012) Clinician and participant chose to start antibiotic treatment Exclusion Criteria: Previously enrolled in the study Allergic or intolerant to amoxicillin, penicillin, or amoxicillin/clavulanate Specific medication concerns: lactating (since safety of clavulanate unknown); taking allopurinol (increased risk of rash); concurrent mononucleosis (increased risk of rash with amoxicillin); chronic kidney disease with glomerular filtration rate < 30; significant hepatic impairment; history of antibiotic-associated colitis Cognitive impairment so that unable to give informed consent or give reliable assessment of improvement Need to use high-dose amoxicillin/clavulanate: treatment with amoxicllin or penicillin within the past month (risk of penicillin-resistant pneumococci), very ill patient (though not ill enough to send to hospital); immunocompromise Need to hospitalize the patient

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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Accepts Healthy Volunteers

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
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: standard dose<br>amoxicillin/clavulanate 875/125 mg + placebo tablet twice a day for 7 days | Drug: standard dose amoxicillin/clavulanate<br>* amoxicillin/clavulanate 875/125 + placebo bid x 7 days<br>|
| Experimental: high dose<br>Time Period I (November 18, 2014-January 5, 2016): extended-release amoxicillin/clavulanate 1000/62.5 mg 2 tablets (by different manufacturer) twice a day for 7 days Time Period 2 (February 6, 2016-February 27, 2017): immediate-release amoxicillin/clavunate 875/125 mg plus standard immediate-release amoxicillin 875 mg twice a day for 7 days | Drug: high dose amoxicillin/clavulanate<br>* Time Period I: extended-release amoxicillin/clavulanate 1000/62.5 two tablets bid x 7 days Time Period 2: immediate-release amoxicillin/clavulanate 875/125 plus amoxicllin 875 bid x 7 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Subjective Improvement - Day 3 (Rating of a Lot Better or no Symptoms) | rating of a lot better or no symptoms | end of 3 days of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| SNOT-16 - Day 3 | Ratings on a scale from 0=none to 3=severe of 16 sinusitis-related symptoms. Total score can range from 0 to 48 (with 48 the most severe possible) of the 16 symptoms. The outcome measure was the mean difference in the ratings of each of the 16 symptoms between day 0 and day 3 (values at day 0 minus values at day 3). | day 0, end of 3 days of treatment | 
| Subjective Improvement - Day 10 | rating of a lot better or no symptoms | end of 10th day | 
| SNOT-16 - Day 10 | Ratings on a scale from 0=none to 3=severe of 16 sinusitis-related symptoms. Total score can range from 0 to 48 (with 48 the most severe possible) of the 16 symptoms. The outcome measure was the mean difference in the ratings of each of the 16 symptoms between day 0 and day 10 (values at day 0 minus values at day 10). | day 0, end of 10th day | 
| Nasal Colonization With Resistant Bacteria | Clinicians performed anterior nasal cultures to look for colonization with penicillin-resistant pneumococci and other pathogens (stopped after participant #231 because of lack of funds). | baseline | 
| Willingness to Take the Study Antibiotic in the Future | whether participants said they would NOT take the antibiotic again | end of 10th day | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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acute sinusitis, amoxicillin/clavulanate, adults, outcomes