Sinusitis, AcutePhase 4NCT03431337

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

A Phase 4 study testing Amoxicillin 875 mg in people with Sinusitis, Acute, run by Paul Sorum, MD at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

Search all trials

Trial 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. . Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Sinusitis, Acute
What is being tested?: Amoxicillin 875 mg
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 157 participants
Where: 1 siteUnited States
Study dates: 26 Feb 2018to 31 May 2020
Phase: Phase 4
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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).

Who cannot join

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

Show all 9Show fewer

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)

Trial locations and contacts

1 site in 1 country.

United States1 site

Albany Medical Center Internal Medicine and Pediatrics
Cohoes, New York, 12047

Other trials in United States

About this study

Official title: Treatment of Acute Sinusitis With High-Dose vs. Standard-Dose Amoxicillin/Clavulanate: A Confirmation Study

Read the 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.

Conditions: Sinusitis, Acute
Being tested: Amoxicillin 875 mg, Placebo (lactase)
Medical subject headings: Sinusitis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Amoxicillin 875 mgDrug
Also called Amoxil
Doubling the dose of amoxicillin by adding amoxicillin 875 to each dose of the standard treatment of amoxicillin/clavulanate 875/125
Placebo (lactase)Dietary supplement
Placebo (in place of additional amoxicillin in experimental arm)

Study groups in NCT03431337
Study group	Role	What they receive
High dose	Experimental	Amoxicillin/clavulanate 875mg/125mg \& amoxicillin 875 mg twice a day x 7 days Receives: Drug: Amoxicillin 875 mg
Standard dose	Active comparator	Amoxicillin/clavulanate 875 mg/125mg \& placebo (lactase) twice a day x 7 days. Receives: Dietary Supplement: Placebo (lactase)

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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
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
Measured: 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
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.
Measured: 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
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.
Measured: At end of 10 days since enrollment
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
Measured: At end of 10 days since enrollment
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.
Measured: At end of 10 days since enrollment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

26 Feb 201831 May 2020

First posted13 Feb 2018
Study start26 Feb 2018
Primary completion31 May 2020
Study completion31 May 2020

Why it stopped: Futility found by interim analysis

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (5)Papers the sponsor has linked to this study.
Other trials for Sinusitis, AcuteStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 4
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
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.
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 157 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03431337
Sponsor's protocol ID: 4993
Status last verified: Jul 2021
First submitted: 7 Feb 2018
Last updated: 12 Aug 2021
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: Yes: De-identified IPD will be made available to other researchers by contacting the corresponding author at sorump@amc.edu.

Publications

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.
PubMed 22438350
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.
PubMed 23076918
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.
PubMed 9493813
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.
PubMed 19564277
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.
PubMed 33755168

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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RecruitingObservational study
Performance and Safety Assessment of the Mechanical Decongestant Seawater Spray Enriched With Essential Oils From Laboratoires Gilbert in Patient With Acute Rhinitis Associated With Nasal Obstruction
Acute Rhinitis, Nasal Obstruction
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Efficacy of Bee Venom Phonophoresis in Treating Chronic Sinusitis:
Chronic Sinusitis, Acute Sinusitis
Not yet recruitingObservational study
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All Sinusitis, Acute trials

Study at a glance

From the registry record, last updated by the sponsor on 12 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Treatment of Acute Sinusitis With High-Dose vs. Standard-Dose Amoxicillin/Clavulanate: A Confirmation Study
ClinicalTrials.gov ID: NCT03431337
Acronym / sponsor ID: 4993
Conditions: Sinusitis, Acute
Phase: Phase 4
Study type: Interventional
Recruitment status: TerminatedReason stopped: Futility found by interim analysis
Enrolment: 157 participants (actual)
Lead sponsor: Paul Sorum, MDUniversity, hospital or other
Study start: 26 Feb 2018 (actual)
Primary completion: 31 May 2020 (actual)
Study completion: 31 May 2020 (actual)
First posted: 13 Feb 2018 (actual)
Results: Posted 12 Aug 2021

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 2
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.

Arm	Type	Receives
High dose	Experimental	Drug: Amoxicillin 875 mgAmoxicillin/clavulanate 875mg/125mg \& amoxicillin 875 mg twice a day x 7 days
Standard dose	Active comparator	Dietary Supplement: Placebo (lactase)Amoxicillin/clavulanate 875 mg/125mg \& placebo (lactase) twice a day x 7 days.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (2 listed)

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).

Key exclusion criteria (9 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Amoxicillin 875 mgAlso: AmoxilDoubling the dose of amoxicillin by adding amoxicillin 875 to each dose of the standard treatment of amoxicillin/clavulanate 875/125	Drug	High dose
Placebo (lactase)Placebo (in place of additional amoxicillin in experimental arm)	Dietary supplement	Standard dose

Primary outcome

Number of Participants With a Global Rating of Improvement of 5 & 6 at the End of 3 Days of Treatment
Time frame: At 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.

5 secondary outcomes

Number of Participants With a Global Rating of Improvement of 5 or 6 at End of 10 Days Since Enrollment
Time frame: 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
Time frame: 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
Time frame: At end of 10 days since enrollment
Balance of Benefits and Detriments
Time frame: At end of 10 days since enrollment
Number of Participants Answering "Yes" to Willingness to Take the Antibiotic Again in the Future
Time frame: At end of 10 days since enrollment

Results and safety

Results posted to the registry on 12 Aug 2021, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
High Dose	78	49
Standard Dose	79	57

Primary outcome: Number of Participants With a Global Rating of Improvement of 5 & 6 at the End of 3 Days of Treatment

Time frame: At end of 3 days of treatment. Count of participants. Unit: Participants

Measure	High Dose n = 66	Standard Dose n = 70
Value	24	31

Population analysed: Participants who provided a Global Rating of Improvement when contacted at the end of 3 days of treatment.

5 secondary outcomes are reported in the full results.

Adverse events

Time frame: 10 days since enrollment. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
High Dose	0 of 78 (0%)	53 of 78 (67.9%)	0 of 78
Standard Dose	0 of 79 (0%)	52 of 79 (65.8%)	0 of 79

Limitations and caveats (from the sponsor): 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

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 12 Aug 2021.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 22438350Chow 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.
Background: PubMed 23076918Lemiengre 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.
Background: PubMed 9493813Canafax 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.
Background: PubMed 19564277Wald 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.
Derived from this study: PubMed 33755168Gregory 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.
Individual participant dataSharing planned: Yes. De-identified IPD will be made available to other researchers by contacting the corresponding author at sorump@amc.edu.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Paul C Sorum, MD, PhD principal investigator

Albany Medical College

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Amoxicillin 875 mg in people with Sinusitis, Acute, run by Paul Sorum, MD at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 2 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 12 Aug 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 12 Aug 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With a Global Rating of Improvement of 5 & 6 at the End of 3 Days of Treatment (time frame: At end of 3 days of treatment). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03431337, which also lists 5 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Aug 2021.