Treatment Strategies for Sinus Infection

(NOSES Trial)

Recruiting at 7 trial locations

Overseen By Lead Project Coordinator

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Daniel Merenstein

Must not be taking: Intranasal corticosteroids

Disqualifiers: Penicillin allergy, Recent antibiotics, Sinus surgery, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

Duration: 14 days

3720 Participants Needed

Trial Summary

What is the purpose of this trial?

Sinus infections are sometimes treated with oral antibiotics or nasal steroid sprays, while some patients get better on their own. Some patients may wait a few days or use common over-the-counter remedies to see if their symptoms improve without further treatment. Sometimes this is enough to help patients wait a few days to see if their infection clears up without needing to use antibiotics or nasal steroid sprays. The overall goal of this clinical trial to see which specific groups of patients benefit more from which intervention or combination of intervention, and which improve with supportive care alone.

Will I have to stop taking my current medications?

The trial requires that you stop using intranasal corticosteroids (nasal sprays with steroids) if you have been using them regularly in the past two weeks and are unwilling to stop while in the study.

What data supports the effectiveness of the drug Amoxicillin/clavulanate for treating sinus infections?

Research shows that Amoxicillin/clavulanate is effective in treating sinus infections, with a study reporting a 93% success rate in patients with bacterial sinusitis caused by Streptococcus pneumoniae. Additionally, children treated with this drug were more likely to be cured compared to those receiving a placebo. ^{1 2 3 4 5}

Is the treatment generally safe for humans?

Amoxicillin/clavulanate, also known as Augmentin or Clavamox, is generally considered safe, but it can cause side effects like diarrhea and, in rare cases, more serious conditions like hepatitis (liver inflammation) and agranulocytosis (a drop in white blood cells). Budesonide nasal spray is not mentioned in the provided research, so no safety data is available for it here. ^{6 7 8 9 10}

How does the drug amoxicillin/clavulanate differ from other treatments for sinus infections?

Amoxicillin/clavulanate is unique because it combines amoxicillin, an antibiotic, with clavulanate, which helps overcome bacterial resistance by inhibiting beta-lactamase enzymes. This makes it effective against bacteria that are resistant to amoxicillin alone, providing broader coverage for treating sinus infections. ^{1 2 3 11 12}

Research Team

Dan Merenstein, MD

Principal Investigator

Georgetown University

Eligibility Criteria

Adults aged 18-65 with symptoms of a sinus infection lasting 1-21 days without improvement can join. Excluded are those with prior sinus surgery, severe complications, weakened immune systems, recent hospitalization or antibiotic use, penicillin allergy, pregnancy/breastfeeding, and inability to consent or follow the study.

Inclusion Criteria

I am between 18 and 65 years old with symptoms of a sinus infection for 1-21 days without getting better.

Exclusion Criteria

I have taken antibiotics in the last month.

I need IV antibiotics or must be admitted to the hospital.

I have had a fever over 102°F recently.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

Baseline to 9 days of symptoms

1 visit (in-person)

Pre-randomization

Participants undergo a waiting period of 9 or more days with options for supportive care

9 days

Daily diary entries

Treatment

Participants are randomly assigned to one of four arms and receive treatment for approximately 14 days

14 days

Daily diary entries and periodic follow-ups

Follow-up

Participants are monitored for safety and effectiveness after treatment

14 days post-randomization

Follow-up interviews at 3, 7, and 14 days post-randomization

Treatment Details

Interventions

• Amoxicillin/clavulanate
• Budesonide nasal spray

Trial Overview The trial is testing if nasal steroids (Budesonide), oral antibiotics (Amoxicillin/clavulanate), or placebo treatments help people with sinus infections recover better. It also aims to identify which patients benefit most from each treatment option.

Participant Groups

Group I: placebo antibiotic plus intranasal corticosteroid Experimental Treatment 3 Interventions

placebo antibiotic plus budesonide

Group II: antibiotic Active Control 2 Interventions

amoxicillin/clavulanate

Group III: antibiotic plus intranasal corticosteroid Active Control 3 Interventions

amoxicillin/clavulanate plus budesonide

Group IV: placebo antibiotic Placebo Group 2 Interventions

placebo antibiotic, amoxicillin/clavulanate

Amoxicillin/clavulanate is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Augmentin for:

• Bacterial infections
• Respiratory tract infections
• Skin and soft tissue infections
• Urinary tract infections

Approved in United States as Augmentin for:

• Lower respiratory tract infections
• Otitis media
• Sinusitis
• Skin and skin structure infections
• Urinary tract infections

Approved in Canada as Clavamox for:

• Bacterial infections
• Respiratory tract infections
• Skin and soft tissue infections
• Urinary tract infections

Who Is Running the Clinical Trial?

Daniel Merenstein

Lead Sponsor

Trials

1

Recruited

3,700+

University of California, Los Angeles

Collaborator

Trials

1,594

Recruited

10,430,000+

University of Washington

Collaborator

Trials

1,858

Recruited

2,023,000+

University of Wisconsin, Madison

Collaborator

Trials

1,249

Recruited

3,255,000+

Medstar Health Research Institute

Collaborator

Trials

202

Recruited

187,000+

Patient-Centered Outcomes Research Institute

Collaborator

Trials

592

Recruited

27,110,000+

Penn State College of Medicine

Collaborator

Trials

1

Recruited

3,700+

Virginia Commonwealth University

Collaborator

Trials

732

Recruited

22,900,000+

References

1. United States pubmed.ncbi.nlm.nih.gov

Comparative effectiveness of amoxicillin versus amoxicillin-clavulanate among adults with acute sinusitis in emergency department and urgent care settings. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

High-dose versus standard-dose amoxicillin/clavulanate for clinically-diagnosed acute bacterial sinusitis: A randomized clinical trial. [2018]

3. United States pubmed.ncbi.nlm.nih.gov

Comparative effectiveness of amoxicillin and amoxicillin-clavulanate potassium in acute paranasal sinus infections in children: a double-blind, placebo-controlled trial. [2016]

4. United States pubmed.ncbi.nlm.nih.gov

Pharmacokinetically enhanced amoxicillin/clavulanate (2,000/125 mg) in acute bacterial rhinosinusitis caused by Streptococcus pneumoniae, including penicillin-resistant strains. [2013]

5. United States pubmed.ncbi.nlm.nih.gov

A combination of amoxicillin and clavulanate every 12 hours vs every 8 hours for treatment of acute bacterial maxillary sinusitis. [2019]

6. Japan pubmed.ncbi.nlm.nih.gov

[Efficacy and safety of potassium clavulanate/amoxicillin (CLAVAMOX) dry syrup in children with otitis media]. [2019]

7. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Comparative efficacy and safety of amoxiclav (amoxicillin clavulanate) and ampicillin in the treatment of acute bacterial sinusitis]. [2013]

8. United States pubmed.ncbi.nlm.nih.gov

Amoxicillin-clavulanic acid-induced hepatitis. [2016]

9. United States pubmed.ncbi.nlm.nih.gov

Amoxicillin/Clavulanic Acid-Induced Agranulocytosis: A Case Report and Review of the Literature. [2020]

10. United States pubmed.ncbi.nlm.nih.gov

Randomized double-blind study comparing 3- and 6-day regimens of azithromycin with a 10-day amoxicillin-clavulanate regimen for treatment of acute bacterial sinusitis. [2021]

11. United States pubmed.ncbi.nlm.nih.gov

Azithromycin versus amoxicillin/clavulanate in the treatment of acute sinusitis. [2019]

12. United States pubmed.ncbi.nlm.nih.gov

Treatment of acute bacterial rhinosinusitis caused by antimicrobial-resistant Streptococcus pneumoniae. [2019]