Sinusitis
Conditions
Keywords
acute sinusitis, amoxicillin/clavulanate, adults, outcomes
Brief summary
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
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.
Interventions
DRUGstandard dose amoxicillin/clavulanate
amoxicillin/clavulanate 875/125 + placebo bid x 7 days
DRUGhigh dose amoxicillin/clavulanate
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
Sponsors
Albany Medical College
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
1. Adult 18 or over 2. Meets definition of acute sinusitis by Infectious Disease Society of America (2012) 3. Clinician and participant chose to start antibiotic treatment
Exclusion criteria
1. Previously enrolled in the study 2. Allergic or intolerant to amoxicillin, penicillin, or amoxicillin/clavulanate 3. 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 4. Cognitive impairment so that unable to give informed consent or give reliable assessment of improvement 5. 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 6. Need to hospitalize the patient
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Subjective Improvement - Day 3 (Rating of a Lot Better or no Symptoms) | end of 3 days of treatment | rating of a lot better or no symptoms |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| SNOT-16 - Day 3 | day 0, end of 3 days of treatment | 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). |
| Subjective Improvement - Day 10 | end of 10th day | rating of a lot better or no symptoms |
| SNOT-16 - Day 10 | day 0, end of 10th day | 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). |
| Nasal Colonization With Resistant Bacteria | baseline | 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). |
| Willingness to Take the Study Antibiotic in the Future | end of 10th day | whether participants said they would NOT take the antibiotic again |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Standard Dose amoxicillin/clavulanate 875/125 mg + placebo tablet twice a day for 7 days
standard dose amoxicillin/clavulanate: amoxicillin/clavulanate 875/125 + placebo bid x 7 days | 159 |
| High Dose 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
high dose amoxicillin/clavulanate: 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 | 156 |
| Total | 315 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Time Period 1 | Lost to Follow-up | 6 | 7 |
| Time Period 1 | Withdrawal by Subject | 6 | 8 |
| Time Period 2 | Lost to Follow-up | 10 | 8 |
| Time Period 2 | Withdrawal by Subject | 9 | 7 |
Baseline characteristics
| Characteristic | Total | High Dose | Standard Dose |
|---|---|---|---|
| Active tobacco use | 39 Participants | 20 Participants | 19 Participants |
| Age, Continuous | 46.9 years STANDARD_DEVIATION 15.4 | 45.9 years STANDARD_DEVIATION 14.8 | 48.0 years STANDARD_DEVIATION 15.9 |
| allergic rhinitis | 162 Participants | 80 Participants | 82 Participants |
| COPD/asthma | 59 Participants | 30 Participants | 29 Participants |
| Day 0 SNOT-16 mean item score | 1.94 units on a scale STANDARD_DEVIATION 0.55 | 1.99 units on a scale STANDARD_DEVIATION 0.55 | 1.89 units on a scale STANDARD_DEVIATION 0.56 |
| Days of illness | 14.5 days STANDARD_DEVIATION 8.4 | 14.3 days STANDARD_DEVIATION 8.1 | 14.8 days STANDARD_DEVIATION 8.8 |
| Diabetes | 31 Participants | 15 Participants | 16 Participants |
| Heart disease | 19 Participants | 8 Participants | 11 Participants |
| History of sinusitis | 123 Participants | 60 Participants | 63 Participants |
| Race and Ethnicity Not Collected | 0 Participants | — | — |
| Sex: Female, Male Female | 223 Participants | 108 Participants | 115 Participants |
| Sex: Female, Male Male | 92 Participants | 48 Participants | 44 Participants |
| Sinusitis category 1 | 204 Participants | 103 Participants | 101 Participants |
| Sinusitis category 2 | 37 Participants | 19 Participants | 18 Participants |
| Sinusitis category 3 | 74 Participants | 34 Participants | 40 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 90 | 0 / 89 | 0 / 69 | 0 / 67 |
| other Total, other adverse events | 30 / 87 | 37 / 80 | 19 / 62 | 27 / 57 |
| serious Total, serious adverse events | 0 / 90 | 0 / 89 | 0 / 69 | 0 / 67 |
Outcome results
Primary
Subjective Improvement - Day 3 (Rating of a Lot Better or no Symptoms)
rating of a lot better or no symptoms
Time frame: end of 3 days of treatment
Population: The number of participants who gave ratings at the end of day 3 of treatment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Standard Dose Time Period I | Subjective Improvement - Day 3 (Rating of a Lot Better or no Symptoms) | 33 Participants |
| High Dose Time Period 1 | Subjective Improvement - Day 3 (Rating of a Lot Better or no Symptoms) | 31 Participants |
| Standard Dose Time Period 2 | Subjective Improvement - Day 3 (Rating of a Lot Better or no Symptoms) | 22 Participants |
| High Dose Time Period 2 | Subjective Improvement - Day 3 (Rating of a Lot Better or no Symptoms) | 33 Participants |
Secondary
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).
Time frame: baseline
Population: All 231 participants were analyzed together regardless of treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Standard Dose Time Period I | Nasal Colonization With Resistant Bacteria | No growth or normal flora | 139 Participants |
| Standard Dose Time Period I | Nasal Colonization With Resistant Bacteria | Methicillin-sensitive Staphylococcus aureus | 32 Participants |
| Standard Dose Time Period I | Nasal Colonization With Resistant Bacteria | Haemophilus influenzae | 25 Participants |
| Standard Dose Time Period I | Nasal Colonization With Resistant Bacteria | Streptococcus pneumoniae | 9 Participants |
| Standard Dose Time Period I | Nasal Colonization With Resistant Bacteria | Moxarella catarrhalis | 9 Participants |
| Standard Dose Time Period I | Nasal Colonization With Resistant Bacteria | Staphylococcus epidermidis | 7 Participants |
| Standard Dose Time Period I | Nasal Colonization With Resistant Bacteria | Methicillin-resistant Staphylococcus aureus | 5 Participants |
Secondary
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).
Time frame: day 0, end of 10th day
Population: The number of participants who gave ratings at day 10.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Standard Dose Time Period I | SNOT-16 - Day 10 | 1.32 units on a scale | Standard Deviation 0.71 |
| High Dose Time Period 1 | SNOT-16 - Day 10 | 1.48 units on a scale | Standard Deviation 0.64 |
| Standard Dose Time Period 2 | SNOT-16 - Day 10 | 1.37 units on a scale | Standard Deviation 0.67 |
| High Dose Time Period 2 | SNOT-16 - Day 10 | 1.40 units on a scale | Standard Deviation 0.73 |
Secondary
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).
Time frame: day 0, end of 3 days of treatment
Population: The number of participants who gave ratings at day 3.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Standard Dose Time Period I | SNOT-16 - Day 3 | .75 units on a scale | Standard Deviation 0.63 |
| High Dose Time Period 1 | SNOT-16 - Day 3 | .87 units on a scale | Standard Deviation 0.59 |
| Standard Dose Time Period 2 | SNOT-16 - Day 3 | .91 units on a scale | Standard Deviation 0.63 |
| High Dose Time Period 2 | SNOT-16 - Day 3 | .97 units on a scale | Standard Deviation 0.69 |
Secondary
Subjective Improvement - Day 10
rating of a lot better or no symptoms
Time frame: end of 10th day
Population: The number of participants who gave a rating at day 10.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Standard Dose Time Period I | Subjective Improvement - Day 10 | 63 Participants |
| High Dose Time Period 1 | Subjective Improvement - Day 10 | 59 Participants |
| Standard Dose Time Period 2 | Subjective Improvement - Day 10 | 35 Participants |
| High Dose Time Period 2 | Subjective Improvement - Day 10 | 40 Participants |
Secondary
Willingness to Take the Study Antibiotic in the Future
whether participants said they would NOT take the antibiotic again
Time frame: end of 10th day
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Standard Dose Time Period I | Willingness to Take the Study Antibiotic in the Future | 8 Participants |
| High Dose Time Period 1 | Willingness to Take the Study Antibiotic in the Future | 11 Participants |
| Standard Dose Time Period 2 | Willingness to Take the Study Antibiotic in the Future | 5 Participants |
| High Dose Time Period 2 | Willingness to Take the Study Antibiotic in the Future | 8 Participants |