Back to resultsTreatment of Acute Sinusitis With High-Dose vs. Standard-Dose Amoxicillin/Clavulanate
Primary Purpose
Sinusitis, Acute
Status
Terminated
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Amoxicillin 875 mg
Placebo (lactase)
Sponsored by
About this trial
This is an interventional treatment trial for Sinusitis, Acute
Eligibility Criteria
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)
Sites / Locations
- Albany Medical Center Internal Medicine and Pediatrics
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
High dose
Standard dose
Arm Description
Amoxicillin/clavulanate 875mg/125mg & amoxicillin 875 mg twice a day x 7 days
Amoxicillin/clavulanate 875 mg/125mg & placebo (lactase) twice a day x 7 days.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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
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.
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.
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
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03431337
Brief Title
Treatment of Acute Sinusitis With High-Dose vs. Standard-Dose Amoxicillin/Clavulanate
Official Title
Treatment of Acute Sinusitis With High-Dose vs. Standard-Dose Amoxicillin/Clavulanate: A Confirmation Study
Study Type
Interventional
2. Study Status
Record Verification Date
July 2021
Overall Recruitment Status
Terminated
Why Stopped
Futility found by interim analysis
Study Start Date
February 26, 2018 (Actual)
Primary Completion Date
May 31, 2020 (Actual)
Study Completion Date
May 31, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Paul Sorum, MD
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
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
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Sinusitis, Acute
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
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
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
Unlabeled bottles of study medications, identified only by participant #, prepared by the pharmacist member of research team. The placebo will be similar in appearance to plain amoxicillin. The pills inside the bottle will be difficult to see until the bottle is opened by the patient.
Allocation
Randomized
Enrollment
157 (Actual)
8. Arms, Groups, and Interventions
Arm Title
High dose
Arm Type
Experimental
Arm Description
Amoxicillin/clavulanate 875mg/125mg & amoxicillin 875 mg twice a day x 7 days
Arm Title
Standard dose
Arm Type
Active Comparator
Arm Description
Amoxicillin/clavulanate 875 mg/125mg & placebo (lactase) twice a day x 7 days.
Intervention Type
Drug
Intervention Name(s)
Amoxicillin 875 mg
Other Intervention Name(s)
Amoxil
Intervention Description
Doubling the dose of amoxicillin by adding amoxicillin 875 to each dose of the standard treatment of amoxicillin/clavulanate 875/125
Intervention Type
Dietary Supplement
Intervention Name(s)
Placebo (lactase)
Intervention Description
Placebo (in place of additional amoxicillin in experimental arm)
Primary Outcome Measure Information:
Title
Number of Participants With a Global Rating of Improvement of 5 & 6 at the End of 3 Days of Treatment
Description
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.
Time Frame
At end of 3 days of treatment
Secondary Outcome Measure Information:
Title
Number of Participants With a Global Rating of Improvement of 5 or 6 at End of 10 Days Since Enrollment
Description
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
Time Frame
At end of 10 days since enrollment
Title
Change From Baseline in the Total Score on the Sinonasal Outcome Test-16 (SNOT-16) at the End of 3 Days of Treatment
Description
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.
Time Frame
At end of 3 days of treatment
Title
Change From Baseline in the Total Score on the Sinonasal Outcome Test-16 (SNOT-16) at the End of 10 Days Since Enrollment
Description
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.
Time Frame
At end of 10 days since enrollment
Title
Balance of Benefits and Detriments
Description
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
Time Frame
At end of 10 days since enrollment
Title
Number of Participants Answering "Yes" to Willingness to Take the Antibiotic Again in the Future
Description
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.
Time Frame
At end of 10 days since enrollment
Other Pre-specified Outcome Measures:
Title
Number of Participants Reporting Any Diarrhea at Day 3 Among Those Self-identified as Prone or Not Prone to Diarrhea
Description
Among those who indicated at enrollment whether prone to diarrhea or not, the number giving ratings of 1, 2, or 3 on diarrhea scale ranging from 0 (none) to 3 (severe)
Time Frame
At the end of 3 days
Title
Number of Participants Reporting Severe Diarrhea at Day 3 Among Those Self-identified as Prone or Not Prone to Diarrhea
Description
Among those reporting proneness to diarrhea or not at enrollment, the number rating 3 on diarrhea scale ranging from 0 (none) to 3 (severe)
Time Frame
At end of day 3
Title
Number of Participants Reporting Any Diarrhea at Day 10 Among Those Self-identified as Prone or Not Prone to Diarrhea
Description
Among those indicating at enrollment a proneness or not to diarrhea, the number giving ratings of 1, 2, or 3 on the diarrhea scale ranging from 0 (none) to 3 (severe)
Time Frame
At 10 days since enrollment
Title
Number of Participants Reporting Severe Diarrhea at Day 10 Among Those Self-identified as Prone or Not Prone to Diarrhea
Description
Among those indicating proneness to diarrhea or not at enrollment, the number who gave a rating of 3 on the diarrhea scale ranging from 0 (none) to 3 (severe)
Time Frame
At 10 days since enrollment
Title
Number of Female Participants Reporting Any Vaginal Symptoms at Day 3 Among Those Self-identified as Prone or Not Prone to Vaginal Itching or Discharge
Description
Female participants contacted after 3 days of treatment were divided into two groups: those who had or had not reported at baseline a proneness to vaginal symptoms. The measure was the number in each group who gave ratings of 1, 2, or 3 on the vaginal symptoms scale, ranging from 0 (none) to 3 (severe), with a higher score indicating more severe symptoms.
Time Frame
After 3 days of treatment
Title
Number of Female Participants Reporting Severe Vaginal Symptoms at Day 3 Among Those Self-identified as Prone or Not Prone to Vaginal Itching or Discharge
Description
Among female participants indicating a proneness or not to vaginal itching or discharge, the number of ratings of 3 on the vaginal symptom scale ranging from 0 (none) to 3 (severe)Female participants contacted after 3 days of treatment were divided into two groups: those who had or had not reported at baseline a proneness to vaginal symptoms. The measure was the number in each group who gave a rating of 1, 3 on the vaginal symptoms scale, ranging from 0 (none) to 3 (severe), with a higher score indicating more severe symptoms.
Time Frame
At the end of 3 days of treatment
Title
Number of Female Participants Reporting Any Vaginal Symptoms at Day 10 Among Those Self-identified as Prone or Not Prone to Vaginal Itching or Discharge
Description
Female participants contacted after 10 days since enrollment were divided into two groups: those who had or had not reported at baseline a proneness to vaginal symptoms. The measure was the number in each group who gave ratings of 1, 2, or 3 on the vaginal symptoms scale, ranging from 0 (none) to 3 (severe), with a higher score indicating more severe symptoms.
Time Frame
At 10 days since enrollment
Title
Number of Female Participants Reporting Severe Vaginal Symptoms at Day 10 Among Those Self-identified as Prone or Not Prone to Vaginal Itching or Discharge
Description
Female participants contacted at 10 days since enrollment were divided into two groups: those who had or had not reported at baseline a proneness to vaginal symptoms. The measure was the number in each group who gave rating of 3 on the vaginal symptoms scale, ranging from 0 (none) to 3 (severe), with a higher score indicating more severe symptoms.
Time Frame
At 10 days since enrollment
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Paul C Sorum, MD, PhD
Organizational Affiliation
Albany Medical College
Official's Role
Principal Investigator
Facility Information:
Facility Name
Albany Medical Center Internal Medicine and Pediatrics
City
Cohoes
State/Province
New York
ZIP/Postal Code
12047
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
De-identified IPD will be made available to other researchers by contacting the corresponding author at sorump@amc.edu.
IPD Sharing Time Frame
Immediately and indefinitely
IPD Sharing Access Criteria
Contact the corresponding author at sorump@amc.edu
Citations:
PubMed Identifier
22438350
Citation
Chow AW, Benninger MS, Brook I, Brozek JL, Goldstein EJ, Hicks LA, Pankey GA, Seleznick M, Volturo G, Wald ER, File TM Jr; Infectious Diseases Society of America. IDSA clinical practice guideline for acute bacterial rhinosinusitis in children and adults. Clin Infect Dis. 2012 Apr;54(8):e72-e112. doi: 10.1093/cid/cir1043. Epub 2012 Mar 20.
Results Reference
background
PubMed Identifier
23076918
Citation
Lemiengre MB, van Driel ML, Merenstein D, Young J, De Sutter AI. Antibiotics for clinically diagnosed acute rhinosinusitis in adults. Cochrane Database Syst Rev. 2012 Oct 17;10:CD006089. doi: 10.1002/14651858.CD006089.pub4.
Results Reference
background
PubMed Identifier
9493813
Citation
Canafax DM, Yuan Z, Chonmaitree T, Deka K, Russlie HQ, Giebink GS. Amoxicillin middle ear fluid penetration and pharmacokinetics in children with acute otitis media. Pediatr Infect Dis J. 1998 Feb;17(2):149-56. doi: 10.1097/00006454-199802000-00014.
Results Reference
background
PubMed Identifier
19564277
Citation
Wald ER, Nash D, Eickhoff J. Effectiveness of amoxicillin/clavulanate potassium in the treatment of acute bacterial sinusitis in children. Pediatrics. 2009 Jul;124(1):9-15. doi: 10.1542/peds.2008-2902.
Results Reference
background
PubMed Identifier
33755168
Citation
Gregory J, Huynh B, Tayler B, Korgaonkar-Cherala C, Garrison G, Ata A, Sorum P. High-Dose vs Standard-Dose Amoxicillin Plus Clavulanate for Adults With Acute Sinusitis: A Randomized Clinical Trial. JAMA Netw Open. 2021 Mar 1;4(3):e212713. doi: 10.1001/jamanetworkopen.2021.2713.
Results Reference
derived
Learn more about this trial
Treatment of Acute Sinusitis With High-Dose vs. Standard-Dose Amoxicillin/Clavulanate
We'll reach out to this number within 24 hrs