Clinical trial NCT02927834
Conditions: Sinusitis
Sponsor: Loma Linda University
Start date: 2015-08-01; Completion date: 2019-01-01
Enrollment: 24 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
Chronic rhinosinusitis is a common disease that effects millions of people world wide. Despite its frequency it is unclear what treatment options are the best for these patients. Typically patients with chronic rhinosinusitis without nasal polyps (CRSsNP) are given a long term antibiotic (3 weeks), nasal steroid sprays, saline nasal irrigation and occasionally oral steroids. Oral steroids benefit patients with chronic rhinosinusitis with nasal polyps (CRSwNP) however their role in non polyp patients is less clear. It is the goal of this study to see if oral steroids benefit the treatment outcomes in those patients with chronic rhinosinusitis without nasal polyps. In addition this study will look to see if a short course (5 day burst) versus a longer course (21 day taper) of oral steroids make a difference in outcomes.

Detailed description:
The investigators will compare patients with CRSsNP who are treated with antibiotics/nasal steroid sprays, and compare them to chronic sinusitis patients who receive antibiotics/nasal steroid spray along with a course of oral steroids. The goal is to determine if oral steroids have a role in CRSsNP, and if so, the most effective dosage.

Arms: arm 1: 1\. Augmentin (amoxicillin/clavulanate 875/125mg) orally (PO) twice a day for 3 weeks. arm 2: Augmentin with 6 day prednisone taper (40mg PO daily (QD) for 2 days, 20mg PO QD for 2 days, 10mg PO QD for 2 days, then stop) arm 3: Augmentin with 21 days prednisone taper (40mg PO QD for 5 days, 30mg PO QD for 5 days, 20mg PO QD for 5 days, 10mg PO QD for 5 days, then stop. )
Interventions: intervention 1: 6 day Prednisone intervention 2: Augmentin intervention 3: 21 day Prednisone
Intervention descriptions: intervention 1: 6 day prednisone burst intervention 2: Antibiotic augmentin for 3 weeks intervention 3: 21 day prednisone burst

Protocol documents:
Prot_000.pdf: 
 
 
 
 
 
 
 
 
 
 
PROTOCOL OUTLINE AND GUIDELINES 
Identifiers: NCT02927834 Unique Protocol ID: 5130196 
Brief Title: Oral Steroids in Chronic Rhinosinusitis Without Nasal Polyps 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Investigators must submit well-organized, detailed information about the study, demonstrating 
sound research design that minimizes risks to the subject. PI should assure that the content 
outlined below is addressed and may exercise some discretion as to how the information is 
organized. The quality and content of the protocol should demonstrate that scientific and merit 
review of the study has occurred at the departmental level prior to submission to the IRB. 
1. PROTOCOL INFORMATION 
Title: Efficacy of broad spectrum antibiotics combined with oral steroids versus 
antibiotics alone in the treatment of chronic rhinosinusitis (CRS) in adults without 
nasal polyposis (CRSsNP) 
Funding Source: None. 
Phase of Study: Phase 4 
Version Date of Protocol: 12/3/2020 
2. PRINCIPAL INVESTIGATOR’S INFORMATION 
Kristin Seiberling, MD. Loma Linda University Department of Otolaryngology Head 
and Neck Surgery, 11234 Anderson Street, Loma Linda CA 92354. Ext 2260, fax 
44819 
3. STUDY PERSONNEL 
Kristin Seiberling, MD – PI 
Christopher Church, MD – Co-investigator 
Christopher Vuong, MD – Resident investigator 
4. STUDY INFORMATION 
Location(s) of Research Activity: Loma Linda Sinus and Allergy Center 
Expected Start/Stop Dates of Research: Start upon IRB approval, will plan to 
conduct study and collect data over 12 months 
Special Time Sensitivities: None 
Type of Research: Interventional 
5. INCLUSION / EXCLUSION CRITERIA 


Inclusion Criteria: 
1. They have three-months of persistent symptoms meeting criteria for chronic rhinosinusits 
as defined by the Taskforce on Rhinosinusitis. 
2. They have a CT-scan in our clinic or have a viewable recent (< 3weeks prior to clinic 
visit) CT-scan with a Lund Mckay score of 6 or greater. A Lund Mckay score of 6 or 
greater is felt to be indicative of at least moderate CRS. 
2 
3. They do not have nasal polyps on initial clinic nasal endoscopy 
4. They are willing to participate in a clinical study 
5. They are between the ages of 18 to 80. 
Exclusion Criteria: 
1. They have a condition in which the use of systemic corticosteroids is contraindicated 
such as diabetes will be excluded. 
2. They are unable to or unwilling to take the prescribed antibiotics or steroids will 
excluded. 
3. They have been treated with a > 3 week course of antibiotics and/or systemic steroids 
will also be excluded. 
4. They have variants of chronic sinusitis known to be refractory to medical therapy such as 
Wegener's granulomatosis, primary ciliary dyskinesia or sarcoidosis. 
5. They have sinusitis secondary to prior surgery, a dental procedure or anatomical 
variants. 
6. They have nasal polyps on physical exam. 
7. They are pregnant. Subjects who are possibly pregnant will be excluded based on history. 
Pregnancy testing is not standard of care for diagnostic imaging. 
8. They have a Lund-Mckay score on CT scan of < 6 
9. They are < 18 or > 80 years old 
6. SUBJECT RECRUITMENT & SCREENING 


Number of Subjects: ~40 
Subject Age Range: ≥18 years of age, ≤80 years of age 
Subject Gender: Both 
Racial/Ethnic Distribution: Any 
Target Study Population: Patients without nasal polyps who suffer from chronic 
rhinosinusitis. 
English/Non-English Speaking Subject Info: Translators will be provided for non- 
English speaking patients 
Certified Translated Consent Form Use: None 
Recruitment Material Type Info: All patients who present to Loma Linda Sinus and 
Allergy center meeting inclusion criteria will be asked to participate 
Vulnerable Subject Info: N/A 
Recruitment Method Info: Patients without nasal polyps as documented by 
endoscopy and who are not currently taking antibiotics or nasal/oral corticosteroids 
will be prospectively recruited. This will be a randomized blinded study. Patients 
will be randomized into three groups- Group 1 will received oral antibiotics (Bactrim 
or Augmentin) nasal steroid sprays (fluticasone) along with nasal saline irrigation , 
Group 2 will receive oral antibiotics, steroid nasal spray and in addition oral steroids 
(prednisone) at a tapered dosage for 6 days, and Group 3 will receive oral 
antibiotics, steroid nasal spray and in addition oral steroids at a tapered dosage for 
20 days. The investigator will be blinded as to which group the subjects are placed. 
Description of consent precautions regarding subject rights and welfare: Informed 
consent will be obtained from all patients after they have been given the opportunity 
to have their questions answered. 
Pregnancy Status Info: Pregnant patients will not be included in study 
3 
7. INFORMED CONSENT PROCESS 


Specific description of informed consent process: Informed consent will be obtained 
from all participating subjects prior to enrollment in the study. (See attached 
informed consent form) The risks, benefits and alternatives will be discussed with 
potential subjects by clinic investigators listed above (Drs. Seiberling, Church and 
Vuong) at time of appointment at Loma Linda Sinus and Allergy center. Patient 
information will be kept private and there will be time for decision-making/discussion 
prior to enrollment in the study. Patient who are able to verbalize/demonstrate their 
understanding and are able to give informed consent will be considered. Subjects will 
be identified by state ID or Driver’s license and will be randomized into one of two 
study groups by flip of a coin. 
Coding system: diagnosis and office visits will be coded in the standard fashion. 
Privacy of Medical and Research Records information/medical records: Patient 
information and study data will be kept as hard copy by PI in locked desk/room and 
some study data will be kept on encrypted/protected flash drive by PI. 
Medical Release forms, HIPAA compliance/authorization form: See attached form 
8. STUDY DESIGN 
a. Background or rationale for this study: Chronic sinus infections (chronic 
sinusitis or CRS) are common conditions that affect millions of Americans. This 
disease can be divided into two main patient groups: Patients with chronic 
rhinosinusitis without nasal polyps (CRSsNP) and those with nasal polyps 
(CRSwNP). We will be focusing on the non-polyp group. While this is a common 
disorder, medical treatments for this condition vary considerably and little is 
known how and why different treatments work in some individuals and not in 
others. Topical nasal steroids and oral antibiotics are the mainstay and 
standard of care for both CRSsNP and CRSwNP. Oral steroids are commonly 
given for both of these sinusitis variants, however their role in non-polyp CRS 
patients is less well delineated. The purpose of this research study is to better 


understand whether orally administered steroids results in superior results 
when compared with nasally sprayed steroids in this population. The 
investigators will compare patients with chronic sinusitis who are treated with 
antibiotics, topical nasal sprayed steroid therapy, and compare them to chronic 
sinusitis patients who receive antibiotics and nasally sprayed steroid therapy 
along with a short course or long course of oral steroids. The goal is to 
determine if oral steroids have a role in CRSsNP, and if so, the most effective 
dosage. 
b. Objectives. To compare the effectiveness of topical nasal steroid sprays, oral 
antibiotics and saline nasal irrigations versus topical nasal steroids, oral 
antibiotics, saline nasal irrigation + oral corticosteroids (prednisone) in CRS 
patients without nasal polyps. 
c. Procedures involved (Research Interventions). Chronological order of all 
research interventions, distinguishing standard of care vs. research 
intervention: 
4 
1. At the time of enrollment nasal endoscopy will be performed to confirm that the 
patient does not have evidence of nasal polyps. Office-based sinus CT scan will 
also be completed on initial visit. Lund-McKay score at initiation of treatment 
will be one a determinate of study eligibility. (Lund-McKay staging system is 
currently the most widely accepted system to radiographically characterize and 
diagnose CRS. A score of 6 or greater indicates significant sinus disease and 
meets inclusion criteria for study. See below table 1 for Lund-McKay staging 
system.) Note: Endoscopy and CT of paranasal sinuses are the standard of care 
for evaluation of patients with symptoms of CRS and will be offered to all patients 
presenting with these symptoms regardless of study enrollment status. 
2. Subjects will be asked to fill out a SNOT 22 survey before the start of therapy. 


(SNOT 20 form attached). 
3. Nasal endoscopy score will also be obtained during initial visit. (Nasal endoscopy 
scoring form attached). This exam is part of the standard of care. 
4. Subjects will be randomized into 3 groups via an electronic random generator 
(see below) 
1. Group 1: Treated with oral antibiotics, nasal steroid spray and saline 
rinses for 3 weeks (standard of care) 
2. Group 2: Treated with above + Prednisone 6 day tapered dosage 
(standard of care) 
3. Group 3: Group 2: Treated with above + Prednisone 20 day tapered 
dosage (standard of care) 
4. Random generator: 
5 
5. Patients will return to office at 4 weeks (following 3 weeks of oral antibiotics, 
nasal steroid spray, nasal saline irrigation + prednisone for patients in Groups 2 
and 3), At that time, patients will be asked to fill out SNOT 22 survey, nasal 
endoscopy and CT scan to assess response to treatment. (standard of care). 
6. At the 4 week follow up, patients will be asked to fill out SNOT 22 survey, and 
undergo nasal endoscopy. (standard of care). 
d. Alternative procedures, if any, that are not included in the study but might be 
advantageous to the subject - None 
e. If any deception is required for validity of this study, explain why this is 
necessary and how subject(s) will be debriefed. - None 
f. Concise review of literature that supports the rationale, objectives, and 
methodology of the proposed study. 
1. Chronic sinus infections (chronic sinusitis or CRS) are common 
conditions that affect millions of Americans. This disease can be divided 


into two main patient groups: Patients with chronic rhinosinusitis without 
nasal polyps (CRSsNP) and those with nasal polyps (CRSwNP). We will 
be focusing on the non-polyp group. While this is a common disorder, 
medical treatments for this condition vary considerably and little is known 
how and why different treatments work in some individuals and not in 
others. Topical nasal steroids and oral antibiotics are the mainstay and 
standard of care for both CRSsNP and CRSwNP. Oral steroids are 
commonly given for both of these sinusitis variants, however their role in 
non-polyp CRS patients is less well delineated. The purpose of this 
research study is to better understand whether orally administered 
steroids results in superior results when compared with nasally sprayed 
steroids in this population, and if so, at which dosage. The investigators 
will compare patients with chronic sinusitis who are treated with 
antibiotics, topical nasal sprayed steroid therapy, and compare them to 
chronic sinusitis patients who receive antibiotics and nasally sprayed 
steroid therapy along with oral steroids. The goal is to determine if oral 
steroids have a role in CRSsNP. (See below for literature review.) 
6 
g. If an Investigational New Drug (IND) is involved, provide the following 
information: (1) name of drug, (2) source of drug, (3) dosage and schedule of 
administration, (4) status with Food and Drug Administration and IND#, (5) 
review of animal studies and previous human studies, (6) reported side effects. 
– Not applicable to this study 
h. For an approved drug used in an experiment, provide similar information: 
1. Fluticasone propionate nasal spray 400mcg qday given as 2 sprays (50mcg 
propionate per spray) to each nostril twice a day daily. Common side effects 
include: Headache. Back pain, minor nosebleed, menstrual cycle disturbance, 


sinus pain, cough, sore throat, sore or white patches inside or around nose 
1. Augmentin (amoxicillin/clavulanate 875/125mg) PO BID for 3 weeks. 
Common side effects: Diarrhea, nausea, rash, urticarial, pruritis, epigastric 
discomfort, vomiting, glossitis, stomatitis, candidiasis, LFT elevation 
2. If allergic to Augmentin: Bactrim DS 
(Trimethoprim/sulfamethoxazole160/800mg) PO BID for 3 weeks. Common 
side effects: Nausea/vomiting, rash, diarrhea, dizziness, utricaria, headache, 
lethargy 
3. Prednisone 6 day taper given as 30mg PO QD for 2 days, 20mg PO QD for 2 
days, 10mg PO QD for 2 days, then stop. Common side effects: Fluid retention, 
increased sweating, headache, insomnia, nervousness, mood swings, edema, 
muscle weakness, BP elevation, facial erythema, menstrual irregularities, 
hypokalemia, intraocular pressure increase, shortness of breath, weight gain. 
4. Prednisone 20 day taper given as 40mg PO QD for 5 days, 30mg PO QD for 5 
days, 20mg PO QD for 5 days, 10mg PO QD for 5 days, then stop. Common side 
effects: Fluid retention, increased sweating, headache, insomnia, nervousness, 
mood swings, edema, muscle weakness, BP elevation, facial erythema, menstrual 
irregularities, hypokalemia, intraocular pressure increase, shortness of breath, 
weight gain. 
5. Nasal saline ad lib 
g. If an Investigational Device (ID) is involved, provide the following 
information: (1) name of device, (2) manufacturer, (3) status with Food and 
Drug Administration and ID#, (4) review of animal studies and previous 
human studies, (5) reported adverse effects. – Not applicable 
9. DATA COLLECTION 
As above. The data which will be collected is clinic nasal endoscopy score, visual 
analogue score (VAS), SNOT 20 score and initial CT of paranasal sinuses with Lund7 


McKay score. Response to treatment as recorded by subjective scoring systems above 
will be recorded in hard copy and be kept by PI in secure, locked drawer. 
10. LABELING & STORAGE OF DATA & SPECIMENS 
Description of consent document storage/time/destroyed/disposed, research records 
and data storage/time/destroyed/disposed, hard copies vs. electronic, research 
specimens storage/time/destroyed/disposed and any special storage conditions 
11. DATA ANALYSIS 
Data will be compiled and statistical analysis will be made using PRISM software 
12. RISK AND INJURY 
This study poses minimal risk 
13. BENEFIT(S) 
This study will demonstrate whether or not oral steroids in addition to antibiotics and 
topical nasal steroids are efficacious in the treatment of CRSsNP. 
14. COMPENSATION 
None 
15. CONFIDENTIALITY 
All patient information and data will be kept confidential 
16. LITERATURE REVIEW 
a. Hissaria P, Smith W, Wormald PJ, Taylor J, Vadas M, Gillis D, Kette F. Short 
course of systemic corticosteroids in sinonasal polyposis: a double-blind, 
randomized, placebo-controlled trial with evaluation of outcome measures. J 
Allergy Clin Immunol. 2006 Jul;118(1):128-33. Epub 2006 May 19. 
b. Hopkins C, Browne JP, Slack R, Lund V, Brown P. The Lund-Mackay staging 
system for chronic rhinosinusitis: how is it used and what does it predict? 
Otolaryngol Head Neck Surg. 2007 Oct;137(4):555-61. 
c. Hopkins C, Gillett S, Slack R, Lund VJ, Browne JP. Psychometric validity of the 
22-item Sinonasal Outcome Test. Clin Otolaryngol. 2009 Oct;34(5):447-54. 
d. Parikh A, Scadding GK, Darby Y, Baker RC. Topical corticosteroids in chronic 


rhinosinusitis: a randomized, double-blind, placebo-controlled trial using 
fluticasone propionate aqueous nasal spray. Rhinology. 2001 Jun;39(2):75-9. 
e. Stankiewicz JA, Chow JM. Cost analysis in the diagnosis of chronic 
rhinosinusitis. Am J Rhinol. 2003 May-Jun;17(3):139-42. 
f. Wallwork B, Coman W, Mackay-Sim A, Greiff L, Cervin A. A double-blind, 
randomized, placebo-controlled trial of macrolide in the treatment of chronic 
rhinosinusitis. Laryngoscope. 2006 Feb;116(2):189-93