A two-week therapy of nitric oxide nasal spray (NONS) vs Placebo (saline nasal spray) initiated immediately after the onset of a new Recurrent Acute Rhinosinusitis (RARS) episode to assess the acceleration to clinical success (cured/much improved symptoms), lack of use of intranasal corticosteroids (INCS) (Day 5, or thereafter) and rescue oral antibiotics (ATBs) (Day 8, or thereafter) after initiation of nitric oxide releasing solution (NORS) platform therapy.
Study Design: This is a multicenter, randomized, double-blind placebo-controlled, two-arm, parallel-group, phase 2 clinical trial to determine the efficacy and safety of NONS to treat recurrent acute (bacterial) rhinosinusitis (RARS). Nitric oxide-releasing solution (NORS) therapy administered as NONS, has the potential to shorten RARS episodes and may reduce the concomitant use of INCS, oral non-steroidal anti-inflammatory drugs (NSAIDS) and oral ATBs used to manage this condition. Suitable candidates will be randomized to a 2-week course of nitric oxide nasal spray (NONS) compared to saline nasal spray (1:1 ratio, administered as five doses daily). RARS symptoms efficacy response will be measured twice daily, after initiation of study medication (Day 1 to Day 15), then once daily to the end of the study (Day 16 to Day 29). The goal of NONS therapy is to accelerate the time to achieve RARS symptoms resolution, defined as a clinical success (cured or much improved sinusitis symptoms; primary endpoint assessment at Day 8), minimize the use of INCS and the avoidance of rescue oral ATBs (both secondary endpoints) over the study period (Day 1 to Day 29). Participants will be enrolled between RARS episodes while asymptomatic, and on study for up to 4 months or until their next recurrence of RARS at which time study procedures and medication begin. Adults (18 years or older) presenting with a history of mild to severe RARS symptoms (nasal obstruction (congestion), purulent nasal discharge, postnasal drip, headache, facial pain), signs (such as facial swelling), and other nonspecific signs/symptoms of fever and malaise are eligible. The primary endpoint is is the time to sinus symptoms resolution, i.e., being cured or much improved (participant reported clinical success) after 7 days of therapy,
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
The Sponsor designed a dual chamber nasal spray bottle for NORS administration. Components are mixed from two chambers to create the final NO-producing formulation. The liquid contains NO at 0.11 ppm\*hour, which acts as a viricidal agent. Instructions for storing, preparing, and administering the study treatment will be provided to participants.
The Sponsor designed a dual-chamber nasal spray bottle for NORS administration. The bottle will be filled with normal saline before being provided to the participant.
Okanegan Clinical Trials
Kelowna, British Columbia, Canada
Richmond Clinical Trials (Okanagan Clinical Trials Satelite Site)
Richmond, British Columbia, Canada
Cliantha Research
Mississauga, Ontario, Canada
Clinical Research of Ontario
Scarborough Village, Ontario, Canada
Primary endpoint is the time to sinus symptoms resolution
To demonstrate superior efficacy of NONS compared to saline nasal spray in the early treatment of RARS. The primary objective is to demonstrate that NONS accelerates the time to achieve clinical success as determined by a higher percentage of participants having resolved or much improved sinusitis symptoms after 7 days of therapy.
Time frame: 8 days
Time (days) to full recovery from sinusitis (participant reported)
To record the rate of recovery for study participants.
Time frame: 29 days
Time (days) to sinus symptoms resolution, i.e., being cured or much improved (participant reported clinical success)
To record the improvement of symptoms among study participants.
Time frame: 29 days
Time (days) to the initiation of rescue oral ATB(s), i.e., treatment failure i.e., treatment failure
To record the frequency of study participants receiving rescue antibiotics.
Time frame: 29 days
Time (days) to initiation of INCS
To record the rate of study participants starting corticosteroids.
Time frame: 29 days
Proportion of participants requiring INCS
To record the fraction of study participants requiring corticosteroids.
Time frame: Day 5, 8, 15 & 29
Proportion of participants requiring rescue oral ATBs
To record the fraction of study participants requiring antibiotics.
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TREATMENT
Masking
QUADRUPLE
Enrollment
162
Intermed Groupe Santé
Chicoutimi, Quebec, Canada
Alpha Recherche Clinique LeBourneuf
Québec, Quebec, Canada
Alpha Recherche Clinique Val-Belair
Québec, Quebec, Canada
Time frame: Day 5, 8, 15 & 29
Proportion of participants recovered from sinusitis
To record the fraction of study participants who recover
Time frame: Day 5, 8, 15 & 29
Proportion of participants with rapidly worsening symptoms requiring the use of INCS and oral ATBs
To record the fraction of study participants whose symptoms required corticosteroids and antibiotics.
Time frame: 29 days
Proportion of participants achieving at least a 9-point improvement change from baseline in Sinonasal Outcome Test (SNOT)-22
To record the fraction of study participants who show improvement in survey scores.
Time frame: Day 8 & 15
Tolerability and safety of NONS
Number of participants with clinically significant changes from baseline in Adverse events
Time frame: 29 days
Proportion of participants with clinically significant changes from baseline in vital signs
Vital sign measurements includes systolic/diastolic blood pressures, pulse rate, respiratory rate and body temperature
Time frame: 29 days
Proportion of participants with clinically significant changes from baseline in laboratory parameters
Laboratory investigation includes hematology and chemistry panels
Time frame: 29 days
Number of participants with clinically significant changes from Baseline in physical examinations
Time frame: 29 days