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

NCT03431337 | Terminated Phase 4 Results FDA Drug

• 1 other identifier: 4993
• Study Type: interventional
• Target: 157
• Locations: 1 country
• Sites: 1

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. .

Conditions

Sinusitis, Acute

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• Number of Participants With a Global Rating of Improvement of 5 or 6 at End of 10 Days Since Enrollment

  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

  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

  At end of 10 days since enrollment

• Balance of Benefits and Detriments

  At end of 10 days since enrollment

• Number of Participants Answering "Yes" to Willingness to Take the Antibiotic Again in the Future

  At end of 10 days since enrollment

Other Outcomes (8)

• Number of Participants Reporting Any Diarrhea at Day 3 Among Those Self-identified as Prone or Not Prone to Diarrhea

  At the end of 3 days

• Number of Participants Reporting Severe Diarrhea at Day 3 Among Those Self-identified as Prone or Not Prone to Diarrhea

  At end of day 3

• Number of Participants Reporting Any Diarrhea at Day 10 Among Those Self-identified as Prone or Not Prone to Diarrhea

  At 10 days since enrollment

Study Arms (2)

High dose

EXPERIMENTAL

Amoxicillin/clavulanate 875mg/125mg \& amoxicillin 875 mg twice a day x 7 days

Drug: Amoxicillin 875 mg

Standard dose

ACTIVE COMPARATOR

Amoxicillin/clavulanate 875 mg/125mg \& placebo (lactase) twice a day x 7 days.

Dietary Supplement: Placebo (lactase)

Interventions

Amoxicillin 875 mg DRUG

Doubling the dose of amoxicillin by adding amoxicillin 875 to each dose of the standard treatment of amoxicillin/clavulanate 875/125

Also known as: Amoxil

High dose

Placebo (lactase) DIETARY_SUPPLEMENT

Placebo (in place of additional amoxicillin in experimental arm)

Standard dose

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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)

Sponsors & Collaborators

• Paul Sorum, MD: lead

Study Sites (1)

Albany Medical Center Internal Medicine and Pediatrics

Cohoes, New York, 12047, United States

Location

Related Publications (5)

• 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.

  PMID: 22438350 BACKGROUND

• 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.

  PMID: 23076918 BACKGROUND

• 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.

  PMID: 9493813 BACKGROUND

• 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.

  PMID: 19564277 BACKGROUND

• 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.

  PMID: 33755168 DERIVED

MeSH Terms

Conditions

Sinusitis

Interventions

Amoxicillin; Lactase

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Paranasal Sinus Diseases; Nose Diseases; Respiratory Tract Diseases; Otorhinolaryngologic Diseases

Intervention Hierarchy (Ancestors)

Ampicillin; Penicillin G; Penicillins; beta-Lactams; Lactams; Amides; Organic Chemicals; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; beta-Galactosidase; Galactosidases; Glycoside Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes

Limitations and Caveats

1. Early termination midway in the study after a preliminary analysis demonstrated futility 2. Underestimation of non-serious adverse effects because of dropouts and difficulty contacting participants

Results Point of Contact

• Title: Dr. Paul Sorum
• Organization: Albany Medical College

sorump@amc.edu

518-262-7500

Study Officials

• Paul C Sorum, MD, PhD

  Albany Medical College

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Internal Medicine and Pediatrics

Model Details: 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.

Study Record Dates

• First Submitted: February 7, 2018
• First Posted: February 13, 2018
• Study Start: February 26, 2018
• Primary Completion: May 31, 2020
• Study Completion: May 31, 2020
• Last Updated: August 12, 2021
• Results First Posted: August 12, 2021

Record last verified: 2021-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Immediately and indefinitely
• Access Criteria: Contact the corresponding author at sorump@amc.edu

Locations

US (1)