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

NCT04163978 | Completed Phase 2 DMC

• 1 other identifier: NOSi-CTP-02
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 1

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.

Conditions

Chronic Sinusitis

Keywords

nitric oxide, sinusitis

Outcome Measures

Primary Outcomes (2)

• 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)

  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)

  42 days

• To assess the safety of NOSi compared to Budesonide on disease specific quality of life in participants with biofilm-associated recalcitrant chronic rhinosinusitis

  Severity and frequency of adverse events as well as clinically significant Changes in laboratory findings, vital signs, histology, olfaction, and methemoglobin levels.

  63 days

Secondary Outcomes (5)

• To evaluate the efficacy of NOSi compared to Budesonide on the reduction of Modified Lund-Kennedy Scores (MLK)

  Days 21, 42, 63

• To evaluate the efficacy of NOSi compared to Budesonide on quality of life improvements (EQ-5D-5L);

  Days 21, 42, 63

• To evaluate the efficacy of NOSi compared to Budesonide on the density of pathogens

  Days 21, 42, 63

• To evaluate the efficacy of NOSi compared to Budesonide on cilia functionality

  Days 43 & 63

• To evaluate the efficacy of NOSi compared to Budesonide on biofilm elimination

  Days 43 & 63

Study Arms (2)

Nitric oxide releasing solution (NOSi)

EXPERIMENTAL

DailyTopical sinus irrigation delivery of 240mL NOSi

Drug: Nitric Oxide

Budesonide -saline

ACTIVE COMPARATOR

Daily Topical sinus irrigation delivery of 240 mL of 1 mg Budesonide-saline

Drug: Budesonide

Interventions

Nitric Oxide DRUG

in situ 240mL nitric oxide releasing sinus irrigation solution

Also known as: Treatment

Nitric oxide releasing solution (NOSi)

Budesonide DRUG

Saline based sinus irrigation 1mg Budesinide solution

Also known as: Comparator

Budesonide -saline

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent must be obtained from the participant prior to entering the study.
• Must be ≥ 19 years of age unless local laws dictate otherwise
• English speaking
• Willing and able to return to the study site for protocol required visits.
• 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
• 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.
• Participant has been on a stable course of only Pulmicort and saline irrigation for a minimum of 30 days prior to randomization
• 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

You may not qualify if:

• Presence of prior history of sinonasal tumors
• 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
• Autoimmune diseases affecting the upper airway eg Systemic lupus erythematosus, Sjögren's syndrome, systemic sclerosis etc
• Immuno-compromised patients, and patients with impairment in mucociliary function (e.g., cystic fibrosis, Kartagener syndrome)
• Severe underlying disease with anticipated survival less than 6 months
• 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
• Has used any investigational drug(s) within 30 days preceding randomization visit (Day 1);
• Suffers from a condition, which, in the opinion of the medical investigator, would compromise their safety and / or their adherence to the study protocol
• Systemic antibiotics, corticosteroids or antifungals within 30 days of randomization
• Intranasal or irrigation with antibiotics, antifungals or antiseptics or any other sinusitis treatment other than Pulmicort within 30 days of randomization
• Has a family member living in the same household, also enrolled or planning to enroll in this study.

Sponsors & Collaborators

• Sanotize Research and Development corp.: lead

Study Sites (1)

St. Paul's Hospital

Vancouver, British Columbia, V6Z 1Y6, Canada

Location

MeSH Terms

Conditions

Sinusitis

Interventions

Nitric Oxide; Therapeutics; Budesonide

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Paranasal Sinus Diseases; Nose Diseases; Respiratory Tract Diseases; Otorhinolaryngologic Diseases

Intervention Hierarchy (Ancestors)

Reactive Nitrogen Species; Free Radicals; Inorganic Chemicals; Nitrogen Oxides; Nitrogen Compounds; Oxides; Oxygen Compounds; Organic Chemicals; Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Amin Javer, MD

  St. Paul's Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Prospective double-blind, randomized, controlled, parallel group

Study Record Dates

• First Submitted: October 31, 2019
• First Posted: November 15, 2019
• Study Start: October 27, 2019
• Primary Completion: May 3, 2022
• Study Completion: May 3, 2022
• Last Updated: June 30, 2022

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)