Topical Irrigation Therapy for CRS (QSIND)
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Participant, Care Provider
Primary Purpose: Treatment
|Official Title:||Efficacy and Safety of Adjuvant Topical Irrigation in the Treatment of Acute Exacerbation of Chronic Rhinosinusitis Following Functional Endoscopic Sinus Surgery (FESS)|
- Change in Microbiome Profile [ Time Frame: Baseline, Week 2, and Week 10 ]Pre and post treatment endoscopically-obtained sinonasal microbiologic cultures.
- Change in Lund-Kennedy Endoscope Score [ Time Frame: Baseline, Week 2, and Week 10 ]Pre and post treatment nasal endoscopy scored with a validated staging system for edema, -scored by an independent blind observer.
- Change in the 22-item Sinonasal Outcomes Test Score [ Time Frame: Baseline, Week 2, and Week 10 ]Pre and post treatment quality of life questionnaires (22-item Sinonasal Outcomes Test [SNOT-22]).
- Change in Sniffin' Stick-12 Score [ Time Frame: Baseline, Week 2 and Week 10 ]Change in olfactory sense from baseline to week 10 will be measured using the Sniffin' Stick-12 system. Patients will smell each "sniffing pen" and record the smell they detect. A score between 0-12 will indicate olfactory sense.
- Rescue Antibiotics [ Time Frame: Week 2 and Week 10 ]The necessity for rescue oral antibiotics for persistent infection.
|Actual Study Start Date:||October 2016|
|Estimated Study Completion Date:||June 2021|
|Estimated Primary Completion Date:||April 2021 (Final data collection date for primary outcome measure)|
Experimental: Quinine Sulfate
Each study participant randomized into the experimental arm will receive 28 tubes with 1mg/ml (6 mls total) of quinine sulfate, as well as 28 3cc syringes with the mucosal atomizing devices. The solutions will be supplied in light-protected tubes. Patients will apply 3 mls of quinine sulfate to each nostril twice per day. Thus the patients will be exposed to a maximum of 12mls or 12.0 mg of quinine per day.
The Investigational Drug Service (IDS) will prepare and record the distribution of the irrigant. The Clinical Research Coordinator or Clinical Research Nurse will pick up the solutions and will demonstrate the application to the subject. The application of the solution is exactly the same as if the study subject were to irrigate with regular saline as part of their daily regimen for chronic rhinosinusitis.
Drug: Quinine Sulfate
Our plan is to first study quinine against saline to determine efficacy and safety. The vast majority of patients with rhinosinusitis utilize low pressure / high volume (240mls) sinonasal lavage to cleanse the sinonasal cavity. The patients will be exposed to a maximum of 12mls or 12.0 mg of quinine. In standard tonic water, quinine is 8.3mg/100mls and thus an 8oz glass of Canada Dry tonic water has 19.6mg of quinine. Thus, the maximum systemic exposure in our study (assuming ingestion of the total nasal administration) is less than drinking one glass of tonic water / day. To put this in context, the therapeutic range of quinine to treat malaria is 10mg/kg true ileal digestibility (TID) (2100mg for a 70kg individual) nearly 200 X the dose the investigators are proposing.
Placebo Comparator: Placebo
The placebo arm will be spiked with Sucrose Octaacetate which has a bitter taste, but does not stimulate sinonasal nitric oxide production.
Each study participant will receive 28 tubes with 0.5mg/ml sucrose octaacetate, as well as 28 3cc syringes with the mucosal atomizing devices. The solutions will be supplied in light-protected tubes.
The placebo arm will mirror the experimental arm exactly, except for the treatment solution contained in the vials.
In order to blind the participants to which arm they have been randomized into, the placebo arm will contain saline solution spiked with 0.5 mg/ml sucrose octaacetate. This solution will produce a bitter flavor similar to the one produced by quinine. There is no evidence that sucrose octaacetate produces nitric oxide production in the sinonasal cavity, nor is there evidence that it has any side effects (it is used to wean babies off of pacifiers) so the investigators feel it is an effective and safe option for a placebo.
To evaluate the physiological differences between quinine-saline irrigations vs. saline-placebo irrigations for acute exacerbation of uncomplicated chronic rhinosinusitis following endoscopic sinus surgery. A secondary objective is to determine if the use of quinine is efficacious as an alternative therapy to treat bacterial rhinosinusitis.
Sinusitis is a common disorder accounting for an estimated 13 million physician office visits in the United States each year. The aggregated cost of sinusitis is approximately $8 billion annually, affecting an estimated 16% of the population in the United States. Despite multiple attempted treatments, including an estimated 550,000 surgeries per year, the disease continues to be a major health problem, both in expenditures and poor quality of life. Recent analysis of data from the National Ambulatory Medical Care Survey and the National Hospital Ambulatory Medical Care Survey from 2006 to 2010 showed that rhinosinusitis accounted for more outpatient antibiotic prescriptions in adults than any other diagnosis.
Chronic rhinosinusitis (CRS) represents a considerable subset of this population and accounts for a significant portion of expenditures and the vast majority of surgeries. It is defined as signs and symptoms of sinusitis lasting more than 12 weeks. Unlike the organisms responsible for acute rhinosinusitis, difficult to treat bacteria such as Pseudomonas aeruginosa, Staphylococcus aureus and Stenotrophomonas multiformia are often offending pathogens in CRS. Their prevalence increases in those patients who have already had sinus surgery and continue to get recurring sinus infections. Staph aureus and gram-negative organisms have been shown to account for roughly 60% of infections in those patients who have previously undergone endoscopic sinus surgery. Due to increasing drug resistance as well as the potential for biofilm formation, there has been an increasing pressure from both patients and clinicians alike to develop alternative treatments to systemic antibiotics. One commonly used alternative in patients who have had previous sinus surgery is topical saline irrigation with and without other topical preparations. Topical irrigations have much greater paranasal sinus penetration in post surgical patients. Commonly used topical preparations include: saline alone or saline mixed with mupirocin, gentamicin, tobramycin, ceftazadine, betadine, manuka honey, baby shampoo, budesonide or mometasone.
The investigators have recently identified a novel arm of upper airway innate immunity mediated by bitter taste receptors. When a subset of airway bitter taste receptors are activated they stimulate the respiratory epithelium to generate nitric oxide, an important component of sinus innate immunity that increases mucociliary clearance as well as diffuses into the mucus where it is bactericidal. A topical therapy to activate these taste receptors may help the sinuses clear infections through this natural innate defense mechanism. While the investigators have identified multiple bitter compounds that stimulate this response, quinine piqued our interest as it activates multiple bitter taste receptors and has already been used in the human nose.
Please refer to this study by its ClinicalTrials.gov identifier: NCT02630472
|Contact: Steven G Brooks, MPH||6107151991||Steven.Brooks2@uphs.upenn.edu|
|United States, Pennsylvania|
|University of Pennsylvania||Recruiting|
|Philadelphia, Pennsylvania, United States, 19104|
|Contact: Steven G Brooks, MPH 610-715-1991 Steven.Brooks2@uphs.upenn.edu|
|Principal Investigator: Nithin D Adappa, MD|