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Topical Irrigation Therapy for CRS (QSIND)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02630472
Recruitment Status : Terminated (Institutional decision)
First Posted : December 15, 2015
Results First Posted : March 13, 2019
Last Update Posted : March 13, 2019
Sponsor:
Information provided by (Responsible Party):
University of Pennsylvania

Tracking Information
First Submitted Date  ICMJE December 9, 2015
First Posted Date  ICMJE December 15, 2015
Results First Submitted Date  ICMJE December 19, 2018
Results First Posted Date  ICMJE March 13, 2019
Last Update Posted Date March 13, 2019
Actual Study Start Date  ICMJE October 2015
Actual Primary Completion Date May 4, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 11, 2015)
Change in Microbiome Profile [ Time Frame: Baseline, Week 2, and Week 10 ]
Pre and post treatment endoscopically-obtained sinonasal microbiologic cultures.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 28, 2017)
  • 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: December 11, 2015)
  • 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.
  • Change in Lund-MacKay CT Score [ Time Frame: Baseline, Week 2 and Week 10 ]
    Change in sinus disease severity from baseline to week 10 will be assessed using the Lund-MacKay CT Score. The physician will stage the severity of the patients' sinusitis with a score from 0-24. A higher score indicates greater opacification of the sinuses (greater inflammation).
Current Other Pre-specified Outcome Measures
 (submitted: December 11, 2015)
Rescue Antibiotics [ Time Frame: Week 2 and Week 10 ]
The necessity for rescue oral antibiotics for persistent infection.
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE Topical Irrigation Therapy for CRS
Official Title  ICMJE Efficacy and Safety of Adjuvant Topical Irrigation in the Treatment of Acute Exacerbation of Chronic Rhinosinusitis Following Functional Endoscopic Sinus Surgery (FESS)
Brief Summary The purpose of the study is to evaluate the physiologic response of quinine-saline irrigations for acute exacerbation of uncomplicated chronic rhinosinusitis following endoscopic sinus surgery. Subjects who have previously had functional endoscopic sinus surgery with acute exacerbation of chronic rhinosinusitis will be randomized to either a quinine-saline or saline-placebo arm. The investigators will measure baseline and follow-up clinical and quality-of-life outcomes for both arms, and then compare the groups at the end of the study period. The investigators' hypothesis is that the participants in the quinine sulfate arm will perform better on all measures as compared to the control arm.
Detailed Description

Overall Objectives:

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.

Background:

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Care Provider)
Primary Purpose: Treatment
Condition  ICMJE
  • Rhinitis
  • Sinusitis
Intervention  ICMJE
  • 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.
  • Drug: Placebo
    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.
Study Arms  ICMJE
  • 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.

    Intervention: Drug: Quinine Sulfate
  • 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.

    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: February 22, 2018)
10
Original Estimated Enrollment  ICMJE
 (submitted: December 11, 2015)
100
Actual Study Completion Date  ICMJE May 4, 2017
Actual Primary Completion Date May 4, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Patients who have undergone Functional Endoscopic Sinus Surgery (FESS)
  2. Purulent drainage on nasal endoscopy
  3. Male or female subjects, 18 years of age or older
  4. Patients seen at the Dept. of Otorhinolaryngology clinic at Hospital of the University of Pennsylvania (HUP), a tertiary care clinic

Exclusion Criteria:

  1. Pregnant women
  2. Immunocompromised patients
  3. Granulomatous diseases with rhinologic manifestations (Wegner's, Sarcoid, Churg-Strauss)
  4. Primary ciliary dyskinesia
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02630472
Other Study ID Numbers  ICMJE 821731
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party University of Pennsylvania
Study Sponsor  ICMJE University of Pennsylvania
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account University of Pennsylvania
Verification Date February 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP