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

Primary Purpose

Chronic Sinusitis

Status

Completed

Phase

Phase 2

Locations

Canada

Study Type

Interventional

Intervention

Nitric Oxide

Budesonide

About this trial

This is an interventional treatment trial for Chronic Sinusitis focused on measuring nitric oxide, sinusitis

Eligibility Criteria

19 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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

Exclusion Criteria:

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.

Sites / Locations

St. Paul's Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Nitric oxide releasing solution (NOSi)

Budesonide -saline

Arm Description

DailyTopical sinus irrigation delivery of 240mL NOSi

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

Outcomes

Primary Outcome Measures

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)

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.

Secondary Outcome Measures

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

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

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

Mean change in EQ-5D-5L index score as compared to control (Scale 0-100; increase indicates worsening)

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

Mean change in pathogen density compared to control; (log10 cfu/g)

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

Proportion of participants with functional cilia which is known to be denuded by biofilm as determined by the saccharin test compared to control

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

Proportion of participants with biofilm elimination compared to control

Full Information

NCT ID

NCT04163978

First Posted

October 31, 2019

Last Updated

June 28, 2022

Sponsor

Sanotize Research and Development corp.

1. Study Identification

Unique Protocol Identification Number

NCT04163978

Brief Title

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

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)

Study Type

Interventional

2. Study Status

Record Verification Date

April 2022

Overall Recruitment Status

Completed

Study Start Date

October 27, 2019 (Actual)

Primary Completion Date

May 3, 2022 (Actual)

Study Completion Date

May 3, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Sanotize Research and Development corp.

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Chronic Sinusitis

Keywords

nitric oxide, sinusitis

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Model Description

Prospective double-blind, randomized, controlled, parallel group

Masking

ParticipantCare ProviderInvestigatorOutcomes 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.

Allocation

Randomized

Enrollment

56 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Nitric oxide releasing solution (NOSi)

Arm Type

Experimental

Arm Description

DailyTopical sinus irrigation delivery of 240mL NOSi

Arm Title

Budesonide -saline

Arm Type

Active Comparator

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Nitric Oxide

Other Intervention Name(s)

Treatment

Intervention Description

in situ 240mL nitric oxide releasing sinus irrigation solution

Intervention Type

Drug

Intervention Name(s)

Budesonide

Other Intervention Name(s)

Comparator

Intervention Description

Saline based sinus irrigation 1mg Budesinide solution

Primary Outcome Measure Information:

Title

Description

Time Frame

42 days

Title

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

Description

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

Time Frame

63 days

Secondary Outcome Measure Information:

Title

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

Description

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

Time Frame

Days 21, 42, 63

Title

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

Description

Mean change in EQ-5D-5L index score as compared to control (Scale 0-100; increase indicates worsening)

Time Frame

Days 21, 42, 63

Title

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

Description

Mean change in pathogen density compared to control; (log10 cfu/g)

Time Frame

Days 21, 42, 63

Title

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

Description

Proportion of participants with functional cilia which is known to be denuded by biofilm as determined by the saccharin test compared to control

Time Frame

Days 43 & 63

Title

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

Description

Proportion of participants with biofilm elimination compared to control

Time Frame

Days 43 & 63

10. Eligibility

Sex

All

Minimum Age & Unit of Time

19 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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 Exclusion Criteria: 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Amin Javer, MD

Organizational Affiliation

St. Paul's Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

St. Paul's Hospital

City

Vancouver

State/Province

British Columbia

ZIP/Postal Code

V6Z 1Y6

Country

Canada

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

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

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