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Nitric Oxide Releasing Sinus Irrigation (NOSi) to Treat Recalcitrant Chronic Rhinosinusitis (RCRS)

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ClinicalTrials.gov Identifier: NCT04163978
Recruitment Status : Recruiting
First Posted : November 15, 2019
Last Update Posted : November 21, 2019
Sponsor:
Information provided by (Responsible Party):
Sanotize Research and Development corp.

Brief Summary:
This a single center, randomized controlled trial to evaluate safety & efficacy of topical nitric oxide releasing sinus irrigation (NOSi) as compared to budesonide-Saline (Control) in the management of biofilm-associated recalcitrant chronic rhinosinusitis (RCRS). It is hypothesized that a daily treatment of NOSi over a 6-week period will be safe and effective at reducing clinical symptoms associated with RCRS.

Condition or disease Intervention/treatment Phase
Chronic Sinusitis Drug: Nitric Oxide Drug: Budesonide Phase 2

Detailed Description:
This is a prospective, single center, Phase 2, double-blinded, randomized, controlled, parallel group trial study. Up to fifty-four (54) participants will be enrolled (based on power analysis based on outcomes from a previous dose-tolerance study. Screening data will be reviewed to determine participant eligibility. Participants who meet all inclusion criteria and none of the exclusion criteria will be entered into the study and randomized in to the Investigational Medicinal Product (IMP) or Non Investigational Medicinal Product (NIMP) at a 2:1 ratio (NOSi:Budesonide). Each participant will be managed as an outpatient for the 42 days of the study. Participants will be administered NOSi or budesonide in saline by self-administration, at home, as a sinus irrigation to their nasopharynx and sinuses once a day. Participants will be asked to return to the clinic for evaluations on Day 21(±2), Day 43(±2) and Day 63 (±2) following the start of study interventions.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 54 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Prospective double-blind, randomized, controlled, parallel group
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: Participants, Investigators, and Assessors/Adjudicators will be blinded to assignment. One unblinded research coordinator at the site to complete the initial and interim dose administration and IMP reconciliation.
Primary Purpose: Treatment
Official Title: Phase 2 Trial to Evaluate Safety & Efficacy of Topical Nitric Oxide Releasing Sinus Irrigation (NOSi) as Compared to Budesonide-Saline (Control) in the Management of Biofilm-Associated Recalcitrant Chronic Rhinosinusitis (RCRS)
Actual Study Start Date : October 27, 2019
Estimated Primary Completion Date : April 30, 2020
Estimated Study Completion Date : June 30, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Sinusitis

Arm Intervention/treatment
Experimental: Nitric oxide releasing solution (NOSi)
DailyTopical sinus irrigation delivery of 240mL NOSi
Drug: Nitric Oxide
in situ 240mL nitric oxide releasing sinus irrigation solution
Other Name: Treatment

Active Comparator: Budesonide -saline
Daily Topical sinus irrigation delivery of 240 mL of 1 mg Budesonide-saline
Drug: Budesonide
Saline based sinus irrigation 1mg Budesinide solution
Other Name: Comparator




Primary Outcome Measures :
  1. To assess the efficacy of NOSi compared to Budesonide on disease specific quality of life in participants with biofilm-associated recalcitrant chronic rhinosinusitis (RCRS) as measured by the Sino-Nasal Outcome Test (SNOT-22) [ Time Frame: 42 days ]
    Proportion of participants experiencing a 9-point reduction in Sino-Nasal Outcome test (SNOT-22) score (0-5 scale of 22 parameters with a total maxmimum score of 110 and an increased value representing worsening of condition)

  2. To assess the safety of NOSi compared to Budesonide on disease specific quality of life in participants with biofilm-associated recalcitrant chronic rhinosinusitis [ Time Frame: 63 days ]
    Severity and frequency of adverse events as well as clinically significant Changes in laboratory findings, vital signs, histology, olfaction, and methemoglobin levels.


Secondary Outcome Measures :
  1. To evaluate the efficacy of NOSi compared to Budesonide on the reduction of Modified Lund-Kennedy Scores (MLK) [ Time Frame: Days 21, 42, 63 ]
    Mean change in MLK score as compared to control (Scale of 0-2 for 6 locations on each side (maximum total score 24); increase represents worsening

  2. To evaluate the efficacy of NOSi compared to Budesonide on quality of life improvements (EQ-5D-5L); [ Time Frame: Days 21, 42, 63 ]
    Mean change in EQ-5D-5L index score as compared to control (Scale 0-100; increase indicates worsening)

  3. To evaluate the efficacy of NOSi compared to Budesonide on the density of pathogens [ Time Frame: Days 21, 42, 63 ]
    Mean change in pathogen density compared to control; (log10 cfu/g)

  4. To evaluate the efficacy of NOSi compared to Budesonide on cilia functionality [ Time Frame: Days 43 & 63 ]
    Proportion of participants with functional cilia which is known to be denuded by biofilm as determined by the saccharin test compared to control

  5. To evaluate the efficacy of NOSi compared to Budesonide on biofilm elimination [ Time Frame: Days 43 & 63 ]
    Proportion of participants with biofilm elimination compared to control



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   19 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Written informed consent must be obtained from the participant prior to entering the study.
  2. Must be ≥ 19 years of age unless local laws dictate otherwise
  3. English speaking
  4. Willing and able to return to the study site for protocol required visits.
  5. Documented diagnosis of chronic sinusitis with biofilm after a treatment of at least 3 months of a combination of well executed sinus surgery, regular irrigation with topical steroids or a mucosal atomization device and surfactants and at least one course of culture directed oral antibiotics
  6. Persistent or worsening symptoms within 30 days of wash-in with budesonide. Specifically, documented by two SNOT-22 scores greater than or equal to 20 indicating stable (within 9 points) or worsening symptoms. SNOT-22 evaluations must be at least 7 days and no more than 30 days apart. Second SNOT-22 must be used as baseline.
  7. Participant has been on a stable course of only Pulmicort and saline irrigation for a minimum of 30 days prior to randomization
  8. Must be willing to use an adequate and documented form of contraception (or abstinence) from the time of the first dose with the IMP until after the last dose of IMP

Exclusion Criteria:

  1. Presence of prior history of sinonasal tumors
  2. Isolated sphenoid sinusitis or other sinus cavities that are not accessible to a nasal/sinus rinse as done by the patient in the head forward position
  3. Autoimmune diseases affecting the upper airway eg Systemic lupus erythematosus, Sjögren's syndrome, systemic sclerosis etc
  4. Immuno-compromised patients, and patients with impairment in mucociliary function (e.g., cystic fibrosis, Kartagener syndrome)
  5. Severe underlying disease with anticipated survival less than 6 months
  6. Females who are pregnant, breastfeeding, or plan to become pregnant during the course of the study up to 1 weeks after the last dose/study visit
  7. Has used any investigational drug(s) within 30 days preceding randomization visit (Day 1);
  8. Suffers from a condition, which, in the opinion of the medical investigator, would compromise their safety and / or their adherence to the study protocol
  9. Systemic antibiotics, corticosteroids or antifungals within 30 days of randomization
  10. Intranasal or irrigation with antibiotics, antifungals or antiseptics or any other sinusitis treatment other than Pulmicort within 30 days of randomization
  11. Has a family member living in the same household, also enrolled or planning to enroll in this study.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04163978


Contacts
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Contact: Laura Samson (604) 806-9926 lsamson2@providencehealth.bc.ca

Locations
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Canada, British Columbia
St. Paul's Hospital Recruiting
Vancouver, British Columbia, Canada, V6Z 1Y6
Contact: Laura Samson    (604) 806-9926    lsamson2@providencehealth.bc.ca   
Sponsors and Collaborators
Sanotize Research and Development corp.
Investigators
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Principal Investigator: Amin Javer, MD St. Paul's Hospital

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Responsible Party: Sanotize Research and Development corp.
ClinicalTrials.gov Identifier: NCT04163978    
Other Study ID Numbers: NOSi-CTP-02
First Posted: November 15, 2019    Key Record Dates
Last Update Posted: November 21, 2019
Last Verified: November 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Sanotize Research and Development corp.:
nitric oxide, sinusitis
Additional relevant MeSH terms:
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Sinusitis
Paranasal Sinus Diseases
Nose Diseases
Respiratory Tract Diseases
Respiratory Tract Infections
Otorhinolaryngologic Diseases
Budesonide
Nitric Oxide
Anti-Inflammatory Agents
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Asthmatic Agents
Respiratory System Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Free Radical Scavengers
Antioxidants
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Endothelium-Dependent Relaxing Factors
Vasodilator Agents
Gasotransmitters
Protective Agents