Multicenter, Randomized, Double-blinded, Placebo-controlled, Phase 2 Clinical Efficacy Study Evaluating Nitric Oxide Nasal Spray (NONS) Compared to Saline Nasal Spray as an Early Treatment for Recurrent Acute Rhinosinusitis (RARS)
Overview
- Phase
- Phase 2
- Status
- Completed
- Enrollment
- 162
- Locations
- 14
- Primary Endpoint
- Primary endpoint is the time to sinus symptoms resolution
Overview
Brief Summary
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.
Detailed Description
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 Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description
A blinded participant number will be assigned to each randomized participant. Site staff/ physician will then dispense a kit labelled with the authorization number generated during randomization to the individual participant. No study investigators, associates performing assessments or participants will be aware of the study medication in the assigned treatments.
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •At least aged 18 years old at the time of consent (19 years depending on the age of majority in the Canadian province/territory).
- •History of recurrent acute bacterial sinusitis (ABS) with at least three episodes in the previous 12 months with at least two episodes requiring ATB therapy (with symptom-free periods between infections).
- •History of at least two moderately severe symptoms of acute rhinosinusitis (anterior (nasal) and posterior (postnasal drip) secretions, nasal obstruction (congestion), headache or facial pain/pressure during a typical RARS episode.
- •If female, be surgically sterile or post-menopausal (no menses for at least 12 months), or if of childbearing potential, must be using an acceptable method of contraception such as a combination estrogen/progestin hormonal contraceptive (oral or injected) for at least 1 month prior to Screening, or such items as an intrauterine device (IUD), intrauterine system (IUS), transdermal hormonal implant, vaginal hormonal ring, or 2 forms of the following: diaphragm, cervical cap, patch, condom, spermicide, or sponge. Total abstinence is permitted. Must agree to agree continue using contraception for the duration of the study medication treatment.
- •If male, be surgically sterile, or agree to use appropriate contraception (latex condom with spermicide) when engaging in sexual activity and agree to not donate sperm for the duration of the study medication treatment.
- •Be reasonable stable health (i.e., diagnosed chronic illnesses that are not deemed stable by the participant's primary care physician), or in the opinion of the Investigator, based on medical history (i.e., absence of any clinically relevant abnormality) during Screening.
- •Be able to understand and provide written, informed consent.
- •Must be able to attend on-site and virtual study visits.
Exclusion Criteria
- •Complicated RARS (orbital or intracranial involvement).
- •Symptoms attributed to sinus disease for longer than 4 weeks.
- •RARS with multiple courses of antimicrobial therapy failures (in previous 2 years, 3 or more episodes treated with 2 or more ATBs).
- •Disease history consistent with severe allergic or seasonal rhinitis (requiring oral cortico-steroids to manage intractable nasal symptoms).
- •Isolated frontal and sphenoidal clinical disease (given the different pathophysiology and etiologic pathogens).
- •History of nasal polyposis.
- •History of abnormal sinus pathology.
- •Previous sinus surgery.
- •Participants with cystic fibrosis.
- •Recurrent moderate epistaxis.
Arms & Interventions
Nitric Oxide Releasing Solution
Nasal spray with nitric oxide releasing solution (NORS) delivered five times per day spaced 1 to 4 hours between each dose while awake.
Maximum volume delivered: 0.56 mL NORS @ 0.11ppm*hrs
Intervention: Nitric Oxide Releasing Solution (Drug)
Placebo
Nasal spray with isotonic saline delivered five times per day spaced 1 to 4 hours between each dose while awake.
Maximum volume delivered: 0.56 mL Saline @ 0.9%
Intervention: Nasal spray with isotonic saline (Device)
Outcomes
Primary Outcomes
Primary endpoint is the time to sinus symptoms resolution
Time Frame: 8 days
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.
Secondary Outcomes
- Proportion of participants requiring rescue oral ATBs(Day 5, 8, 15 & 29)
- Proportion of participants achieving at least a 9-point improvement change from baseline in Sinonasal Outcome Test (SNOT)-22(Day 8 & 15)
- Tolerability and safety of NONS(29 days)
- Proportion of participants with clinically significant changes from baseline in vital signs(29 days)
- Proportion of participants with clinically significant changes from baseline in laboratory parameters(29 days)
- Time (days) to full recovery from sinusitis (participant reported)(29 days)
- Time (days) to sinus symptoms resolution, i.e., being cured or much improved (participant reported clinical success)(29 days)
- Time (days) to the initiation of rescue oral ATB(s), i.e., treatment failure i.e., treatment failure(29 days)
- Time (days) to initiation of INCS(29 days)
- Proportion of participants requiring INCS(Day 5, 8, 15 & 29)
- Proportion of participants recovered from sinusitis(Day 5, 8, 15 & 29)
- Proportion of participants with rapidly worsening symptoms requiring the use of INCS and oral ATBs(29 days)
- Number of participants with clinically significant changes from Baseline in physical examinations(29 days)