Treatment Strategies for Sinus Infection

(NOSES Trial)

Recruiting at 8 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine the most effective treatments for sinus infections. It compares several approaches: using an antibiotic (amoxicillin/clavulanate, also known as Augmentin or Clavamox), using the antibiotic with a nasal spray (budesonide), or using placebos (inactive treatments) for both. The goal is to assess whether these treatments help some people recover or if they improve on their own with simple care. Individuals who have experienced sinus infection symptoms for 1-21 days without improvement, or who worsened after a recent cold, might be suitable candidates for this trial. As a Phase 4 trial, this research seeks to understand how these already FDA-approved treatments benefit more patients.

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 is the safety track record for these treatments?

Research has shown that amoxicillin/clavulanate is commonly used to treat bacterial infections, such as sinus infections, and is generally safe for most people. However, like any medicine, it can cause side effects, including an upset stomach, diarrhea, and skin rash.

When combined with budesonide, a nasal spray, the treatment remains well-tolerated. Studies suggest that nasal sprays like budesonide can help with symptoms and are safe when added to antibiotics like amoxicillin/clavulanate. Most people do not experience serious side effects from this combination. It is important to consult a healthcare provider if there are concerns, especially if allergies or other health issues are present. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about these treatments because they explore different strategies for tackling sinus infections more effectively. Unlike the standard care that typically involves antibiotics alone, one treatment combines the antibiotic amoxicillin/clavulanate with an intranasal corticosteroid, budesonide. This combination aims to not only fight the bacterial infection but also reduce inflammation in the nasal passages, potentially enhancing recovery. Additionally, by comparing these combinations to placebo treatments, researchers hope to clarify how much added benefit the corticosteroid brings, offering more refined treatment options in the future.

What evidence suggests that this trial's treatments could be effective for sinus infections?

This trial will compare different treatment strategies for sinus infections. Participants in one arm will receive amoxicillin/clavulanate, while another arm will receive a placebo antibiotic. Additionally, some participants will receive amoxicillin/clavulanate combined with budesonide nasal spray, and others will receive a placebo antibiotic with budesonide. Research has shown that amoxicillin/clavulanate doesn't significantly reduce sinusitis symptoms compared to other similar antibiotics. Studies found no clear benefits between regular and high doses of this antibiotic combination for treating acute sinusitis. Adding budesonide, a nasal spray, may help improve symptoms when used with antibiotics. Research indicates that budesonide can effectively reduce nasal symptoms and provide relief. Overall, using both amoxicillin/clavulanate and budesonide together might offer better results than using antibiotics alone. ^{6 7 8 9 10}

Who Is on the Research Team?

Dan Merenstein, MD

Principal Investigator

Georgetown University

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8208653/

Comparative effectiveness of amoxicillin versus ... There was no difference in sinusitis‐related return visits between amoxicillin (4.9%) and amoxicillin‐clavulanate (5.1%) (adjusted odds ratio [ ...

2. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2777780

High-Dose vs Standard-Dose Amoxicillin Plus Clavulanate ... In this randomized clinical trial, we did not find a benefit to patients of treating clinically diagnosed acute bacterial sinusitis with high- ...

3. aafp.org aafp.org/pubs/afp/issues/2021/1000/p423.html

High-Dose Amoxicillin/Clavulanate No Better than ... This study found no significant difference between the standard-dose and high-dose regimens of amoxicillin/clavulanate for treating acute sinusitis in adults.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT03431337

Treatment of Acute Sinusitis With High-Dose vs. Standard ... Comparative-effectiveness study of the treatment of acute bacterial sinusitis with amoxicillin/clavulanate 875mg/125mg bid for 7 days with or without the ...

5. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/full/10.1002/emp2.12465

Comparative effectiveness of amoxicillin versus ... There was no difference in sinusitis-related return visits between amoxicillin (4.9%) and amoxicillin-clavulanate (5.1%) (adjusted odds ratio [ ...

6. mayoclinic.org mayoclinic.org/drugs-supplements/amoxicillin-and-clavulanate-oral-route/description/drg-20072709

Amoxicillin and clavulanate (oral route) - Side effects & ... Amoxicillin and clavulanate combination is used to treat bacterial infections in many different parts of the body (eg, ear, lungs, sinus, skin, urinary tract).

7. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK538164/

Amoxicillin Clavulanate - StatPearls - NCBI Bookshelf - NIH Amoxicillin-clavulanate is also indicated for treating acute bacterial rhinosinusitis ... The pharmacist can check dose and duration, provide antibiogram data, ...

8. jamanetwork.com jamanetwork.com/journals/jamaotolaryngology/fullarticle/220494

A Combination of Amoxicillin and Clavulanate Every 12 ... Amoxicillin and clavulanate given every 12 hours is as effective and as safe as administration every 8 hours for the treatment of acute bacterial maxillary ...

9. psnet.ahrq.gov psnet.ahrq.gov/web-mm/antibiotics-urisinusitis-simple-decision-gone-bad

Antibiotics for URI/Sinusitis—A Simple Decision Gone Bad Beta-lactam antibiotics such as amoxicillin are generally quite safe, but prescribers and patients must be aware of a wide range of potential adverse effects, ...

10. uptodate.com uptodate.com/contents/uncomplicated-acute-sinusitis-and-rhinosinusitis-in-adults-treatment

Uncomplicated acute sinusitis and rhinosinusitis in adults These agents have broader coverage and lower rates of resistance compared with amoxicillin or doxycycline. Specific choice of therapy depends on ...