Clinical trial NCT03431337: 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
Overall status: TERMINATED
Phase: PHASE4
Conditions: Sinusitis, Acute
Lead sponsor: Albany Medical College
Sponsor class: OTHER
First posted: 2018-02-13
Enrollment: 157
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 1. 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.
2. If they do not meet exclusion criteria, they will be offered enrollment in the study.
3. 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).
4. Outcomes will be assessed, by telephone or over the web (through Qualtrics), at 3 and 10 days after enrollment.
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

1. Adults 18 and older who are patients at the Albany Medical Center Internal Medicine and Pediatrics practice (study site).
2. 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:

1. Previous enrollment in the current study
2. Allergy or intolerance to any penicillin or to amoxicillin/clavulanate
3. Serious hypersensitivity reaction to any beta lactam
4. 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
5. 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
6. 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
7. Cognitive impairment, so unable to give reliable symptom ratings (even if a health proxy can give consent)
8. Pregnant women and nursing mothers
9. 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)

Primary outcomes:
measure: Number of Participants With a Global Rating of Improvement of 5 & 6 at the End of 3 Days of Treatment
timeFrame: At end of 3 days of treatment
Secondary outcomes:
measure: Number of Participants With a Global Rating of Improvement of 5 or 6 at End of 10 Days Since Enrollment
timeFrame: At end of 10 days since enrollment
measure: Change From Baseline in the Total Score on the Sinonasal Outcome Test-16 (SNOT-16) at the End of 3 Days of Treatment
timeFrame: At end of 3 days of treatment
measure: Change From Baseline in the Total Score on the Sinonasal Outcome Test-16 (SNOT-16) at the End of 10 Days Since Enrollment
timeFrame: At end of 10 days since enrollment
measure: Balance of Benefits and Detriments
timeFrame: At end of 10 days since enrollment
measure: Number of Participants Answering "Yes" to Willingness to Take the Antibiotic Again in the Future
timeFrame: At end of 10 days since enrollment
Other outcomes:
measure: Number of Participants Reporting Any Diarrhea at Day 3 Among Those Self-identified as Prone or Not Prone to Diarrhea
timeFrame: At the end of 3 days
measure: Number of Participants Reporting Severe Diarrhea at Day 3 Among Those Self-identified as Prone or Not Prone to Diarrhea
timeFrame: At end of day 3
measure: Number of Participants Reporting Any Diarrhea at Day 10 Among Those Self-identified as Prone or Not Prone to Diarrhea
timeFrame: At 10 days since enrollment
measure: Number of Participants Reporting Severe Diarrhea at Day 10 Among Those Self-identified as Prone or Not Prone to Diarrhea
timeFrame: At 10 days since enrollment
measure: 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
timeFrame: After 3 days of treatment
measure: 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
timeFrame: At the end of 3 days of treatment
measure: 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
timeFrame: At 10 days since enrollment
measure: 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
timeFrame: At 10 days since enrollment
Locations:
city: Cohoes
country: United States
facility: Albany Medical Center Internal Medicine and Pediatrics
state: New York
Study officials:
affiliation: Albany Medical College
name: Paul C Sorum, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
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.
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.
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.