Duration of Antibiotic Therapy as Part of Maximal Medical Therapy for Chronic Rhinosinusitis

Sinusitis Clinical Trial

Official title:

A Randomized Cohort Trial Evaluating Duration of Antibiotic Therapy as Part of Maximal Medical Therapy for Chronic Rhinosinusitis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01825408
• Other study ID #: 12-2377
• Status: Completed
• Phase: Phase 4
• First received: March 18, 2013
• Last updated: June 7, 2016
• Start date: February 2013
• Est. completion date: June 2014

Study information

• Verified date: June 2016
• Source: University of North Carolina, Chapel Hill
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine the best duration(3 versus 6 weeks) of antibiotics as part of maximal medical therapy for treating chronic sinusitis and thus preventing patients from having to have sinus surgery. The hypothesis is that in the context of maximal medical therapy 3 weeks of antibiotics is not worse than 6 weeks of antibiotics at successfully treating chronic sinusitis.

Description:

OVERVIEW This is a prospective randomized cohort study assessing duration of antibiotics (3 vs 6 weeks) as part of maximal medical therapy for chronic rhinosinusitis. Up to 100 subjects will be prospectively enrolled from patients visiting the Department of Otolaryngology-Head and Neck Surgery clinics at UNC Hospitals.

INITIAL CLINIC VISIT At the time of a clinical visit, the attending otolaryngologists will identify their patients with chronic rhinosinusitis (CRS) who are appropriate for maximal medical treatment, including antibiotics. They will introduce the study to these patients and invite them to learn more about it.

If the patient is interested in learning more about the study, the study coordinators will be contacted to provide additional information and, if the patient would like to participate in the study, provide informed consent.

If the patient is a premenopausal woman, she will be asked if she is pregnant or breastfeeding.

If she is either of these, she will be excluded from the study. All remaining women will receive a urine pregnancy test. If this urine pregnancy test is positive, the patient will be excluded from the study. Thus, for premenopausal female patients, a negative urine pregnancy test is necessary for inclusion in the study. These women will be informed that they should use an effective method of birth control during the study:

• Combined oral contraceptives

• Patch contraceptives

• Vaginal ring contraceptives

• Injectable contraceptives

• Implantable contraceptives

• Intrauterine devices or intrauterine systems

• Tubal ligation

• Barrier methods of contraception (male condom, female condom, cervical cap with spermicide, or diaphragm with spermicide)

• Vasectomy of your partner in a monogamous relationship

Women enrolled in this study will be informed that if they have a failure of birth control method during the course of the study or become pregnant during the study, they will be withdrawn from the study and further treatment will be decided according to the clinical withdrawn from the study and further treatment will be decided according to the clinical expertise of the treating otolaryngologist.

• The study coordinators will assign the patients a unique Subject ID that will be used on all patient forms with the exception of the informed consent documents and HIPAA authorization forms.

• The patient will fill out a demographics and past medical history form.

• The patient will fill out two quality of life surveys: the Rhinosinusitis Disability Index (RSDI) and the Chronic Sinusitis Survey (CSS).

• Video recorded nasal endoscopy will be performed by the attending physician. The video file will be stored initially on a portable storage drive that will contain no patient identifiers. The file will be identified only with the SubjectID. The patient's face will not be recorded in the video. The file on the portable storage drive will be transferred to a password protected computer in the locked office of the principal investigator.

• Using a random-number generator, the patient will be randomized to receive either 3 or 6 weeks of antibiotics.

• The subject will initially be given a prescription for empiric antibiotics.The choice of empiric antibiotics will differ based on the patient's nasal polyposis status:

• If the subject has CRS with nasal polyposis (CRSwNP), s/he will be given Doxycycline 100mg BID or if allergic to doxycycline, then Augmentin 875mg BID for either 3 or 6 weeks duration. These patients will also receive a course of Prednisone (30mg x 3d, 20mg x 3d, 10mg x3d, 10mg every other day for 6 days (3 doses)) which is standard of care treatment for CRSwNP.

• If the subject has CRS without Nasal Polyposis (CRSwNP), s/he will be given Azithromycin 250mg daily, or if allergic to azithromycin, then Augmentin 875mg BID for either 3 or 6 weeks duration.

• If purulent nasal discharge is present that is appropriate for culture, the otolaryngologists will send this for culture and sensitivity analysis, which they would normally do as part of their routine clinical care. The patients will be informed that if their culture and sensitivity analysis indicates that they have an infection that can be treated with a less broad-spectrum antibiotic, then they will be prescribed culture-directed antibiotics. Otherwise, the patient can continue empiric antibiotics as previously specified.

• All study participants will also be prescribed standard of care intranasal steroids, and encouraged to perform BID saline sinus irrigation and use yogurt/over the counter probiotics to reduce GI side effects of antibiotics.

AFTER THE INITIAL CLINIC VISIT

The study personnel will access the patient's medical record via WebCIS to:

• Record the patient's allergy status, CBC with differential and IgE at the time of the initial visit. CBC and IgE labs are part of the routine clinical care for CRS. If these are not obtained during the initial clinic visit, they will be obtained at a later clinic visit (visit 2 or future pre-operative visit)

• View the patient's pre-treatment sinus CT scan and calculate a blinded Lund-Mackay score.

4-5 WEEKS AFTER BEGINNING TREATMENT

For subjects randomized to the 3 week antibiotic group, these subjects will been seen in clinic.

During this visit (study visit #2), subjects will complete the RSDI and CSS. Subjects will be asked about antibiotic compliance and side effects. Recommendation for sinus surgery will be evaluated with video-recorded nasal endoscopy and a sinus CT.

For subjects randomized to the 6 week antibiotic group, these subjects will be contacted by phone by the study coordinator to assess side effects and medication compliance.

7-8 WEEKS AFTER BEGINNING TREATMENT

For subjects randomized to the 6 week antibiotic group, these subjects will been seen in clinic.

During this visit (study visit #2), subjects will complete the RSDI and CSS. Subjects will be asked about antibiotic compliance and side effects. Recommendation for sinus surgery will be evaluated with video-recorded nasal endoscopy and a sinus CT.

At any of these study visits or a potential pre-operative visit, subjects will have blood drawn to record IgE and CBC with differential. These labs are routinely ordered in CRS both to characterize the disease and also for pre-operative planning.

All video recorded nasal endoscopies will be blindly scored by Drs. Senior, Ebert, and Zanation with the Lund-Kennedy scoring system. All sinus CTs will be scored with the Lund-Mackay scoring system.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 37
• Est. completion date: June 2014
• Est. primary completion date: June 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 99 Years

Eligibility

Inclusion Criteria:

• Diagnosis of chronic rhinosinusitis

• 18 years of age or older

• English speaking

Exclusion Criteria:

• Pregnant or breastfeeding women

• vasculitis

• cystic fibrosis

• primary ciliary dyskinesia

• allergic fungal sinusitis

• gross immunodeficiency

• current use of chemotherapy

• insulin-dependent diabetes mellitus

• recent trial of maximal medical therapy

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Sinusitis

Intervention

Drug:
• Doxycycline
Subjects with CRSwNP who are not allergic to doxycycline will receive Doxycycline 100mg BID for either 3 or 6 weeks duration.
• Azithromycin
Subjects with CRS without Nasal Polyposis (CRSwNP)who are not allergic to azithromycin will be given Azithromycin 250mg daily for either 3 or 6 weeks duration.
• Augmentin
If a subject in any of the study arms is allergic to the medication he/she is supposed to receive, he/she will be given Augmentin 875mg BID for either 3 or 6 weeks duration

Locations

Country	Name	City	State
United States	Department of Otolaryngology-Head and Neck Surgery clinics at UNC Hospitals	Chapel Hill	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
University of North Carolina, Chapel Hill

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of patients recommended for sinus surgery after 3 weeks of antibiotic therapy	Recommendation for sinus surgery after completion of maximal medical therapy is determined by the subject's treating physician and is based on two citeria: (1) persistence of symptoms and (2) objective evidence of disease on post-treatment sinus CT scan or nasal endoscopy. Symptomatic improvement of sinusitis symptoms will be assessed by: patient self report, change in Chronic Sinusitis Survery (CSS) score and change in RhinoSinusitis Disibility Index (RSDI) score relative to initial pre-antibiotic CSS and RSDI survey scores.	4-5 weeks after starting antibiotics	No
Primary	Number of patients recommended for sinus surgery after 6 weeks of antibiotic therapy	Recommendation for sinus surgery after completion of maximal medical therapy is determined by the subject's treating physician and is based on two citeria: (1) persistence of symptoms and (2) objective evidence of disease on post-treatment sinus CT scan or nasal endoscopy. Symptomatic improvement of sinusitis symptoms will be assessed by: patient self report, change in Chronic Sinusitis Survery (CSS) score and change in RhinoSinusitis Disibility Index (RSDI) score relative to initial pre-antibiotic CSS and RSDI survey scores.	7-8 weeks after initiating antibiotics	No
Secondary	Change in Quality of Life after 3 weeks of antibiotics	Quality of life will be measured at the initial clinic visit and again 4-5 weeks after starting antibiotics. The quality of life assessments used in this study are the Chronic Sinusitis Survey and the RhinoSinusitis Disability Index.	4-5 weeks after starting antibiotics	No
Secondary	Change in Quality of Life after 6 weeks of antibiotics	Quality of life will be measured at the initial clinic visit and again 7-8 weeks after starting antibiotics. The quality of life assessments used in this study are the Chronic Sinusitis Survey and the RhinoSinusitis Disability Index.	7-8 weeks after starting antibiotics	No
Secondary	Change in Nasal endoscopy scores after 3 weeks of antibiotics	Nasal endoscopy is a routine standard of care procedure to assess the sinuses. It will be performed at the initial clinic visit and again at the follow up visit. Nasal endoscopies will be scored with the Lund-Kennedy scoring system.	4-5 weeks after starting antibiotics	No
Secondary	Change in Nasal Endoscopy Score following 6 weeks of antibiotics	Nasal endoscopy is a routine standard of care procedure to assess the sinuses. It will be performed at the initial clinic visit and again at the follow up visit. Nasal endoscopies will be scored with the Lund-Kennedy scoring system.	7-8 weeks after starting antibiotics	No
Secondary	Change in CT Score after 3 weeks of antibiotics	A sinus CT within 3 months of study initiation will be graded and compared with a standard of care post-treatment CT scan using the Lund-Mackay CT scoring system.	4-5 weeks after starting antibiotics	No
Secondary	Change in CT Score after 6 weeks of antibiotics	A sinus CT within 3 months of study initiation will be graded and compared with a standard of care post-treatment CT scan using the Lund-Mackay CT scoring system.	7-8 weeks after starting antibiotics	No
Secondary	Number of patients with antibiotic side effects after a 3 week course of antibiotics	The most frequent side effect of antibiotics is GI upset. At the follow up visit, subjects will be asked about their medication compliance and what, if any, side effects they experienced.	4-5 weeks after starting antibiotics	Yes
Secondary	Number of subjects with antibiotic side effects after a 6 week course of antibiotics	The most frequent side effect of antibiotics is GI upset. 4-5 weeks after starting antibiotics, subjects in the 6-week of antibiotic group will be contacted by the study coordinators and medication compliance and side effects will be assessed. Any adverse outcomes will be reported to the primary investigator. At the follow up visit, subjects will be asked about their medication compliance and what, if any, side effects they experienced.	4-5 weeks and 7-8 weeks after initiating antibiotics	Yes