Evaluation of Two Doses of Nitric Oxide (NO) Given Intermittently Via Inhalation to Subjects With Bronchiolitis
Condition: Bronchiolitis Acute
MeSH terms: Bronchiolitis
Study type: Interventional
Phase: Phase 2

Summary: 
      Prospective, Double-Blinded, Randomized, Multi-Center Study for Evaluation of Two Doses of
      Nitric Oxide (NO) Given Intermittently Via Inhalation to Subjects With Bronchiolitis

      The proposed study judiciously expands these observations for use of NO treatment in
      pediatric patients with bronchiolitis aged less than 12 months. The intermittent dosing
      strategy used in this study has been selected to minimize the potential for adverse effects.
      The inclusion of two doses in the proposed pilot study is intended to determine a dose
      response effect and select a dose that is optimally safe and effective. The primary endpoint
      evaluation of time to fit for discharge will provide an effective objective measurement for
      the treatment effectiveness compared to standard supportive treatment of bronchiolitis.

      Primary objective:

      • Assess whether Nitric Oxide (NO) administered intermittently in 2 concentrations (via
      inhalation for 40 minutes 4 times per day for up to 5 consecutive days) in addition to
      Standard Supportive Treatment (SST) shortens the recovery time of infants with bronchiolitis,
      compared to SST alone.

      Secondary objectives:

        -  Time to achieve O2 saturation of ≥ 92 % sustained for at least 2 hours

        -  Reduction in hospital Length of Stay (LOS)

        -  Time to achieve mTal score of ≤ 5

      Safety objectives: Characterize the safety of 2 doses of NO intermittent inhalation treatment
      therapy as measured by Adverse Events (AE) - number and percentage of subjects that
      experience AEs - and Serious Adverse Events (SAEs).

      A total of 90 subjects will be enrolled into the study and randomized in a 1:1:1 ratio to
      receive the study treatments.

      Treatment administration: Treatment blindness will be kept by designation of blinded and
      un-blinded team members.The blinded staff will be performing the study assessment procedures
      and the un-blinded team will be administering the actual treatment.

      Subjects' parents/legal guardian will be contacted for a follow up phone call at days 14+5
      and 30+5 from the date of enrollment of the subject into the study.
    

Detailed description: 
      Prospective, Double-Blinded, Randomized, Multi-Center Study for Evaluation of Two Doses of
      Nitric Oxide (NO) Given Intermittently Via Inhalation to Subjects With Bronchiolitis

      Bronchiolitis is a viral disease, widely spread amongst young children with significant
      mortality in some cases and no specific treatment available, besides supportive treatment of
      O2 and hydration; therefore, there is an identified unmet medical need to develop a treatment
      strategy for children with bronchiolitis.

      When the immune system's NO generating ability is overwhelmed or compromised, infection and
      disease occur. Increasing the body's ability to produce more NO through gene therapy or
      synthetic NO donor drugs is of interest in medicine.

      NO, by itself, is an essential part of the innate defense mechanism of the human immune
      system which becomes up-regulated by the inducible NO synthase (iNOS) during various
      inflammatory conditions and during microbial and viral infections. This suggests that NO
      treatment in appropriate concentrations is highly relevant for children with bronchiolitis.

      The two previous pilot studies conducted by Beyond Air (formerly known as AIT) found that
      intermittent exposure to was safe and well tolerated in pediatric subjects with acute
      bronchiolitis age 0-12 months and showed a trend in reduction in the length of
      hospitalization. The overall frequency of adverse events was found to be similar between the
      control and NO treated groups and intermittent exposure at 160 ppm did not result in exposure
      to unsafe Nitric Dioxide (NO2) levels or had a cumulative effect on MetHb levels.

      The proposed study judiciously expands these observations for use of NO treatment in
      pediatric patients with bronchiolitis aged less than 12 months. The intermittent dosing
      strategy used in this study has been selected to minimize the potential for adverse effects.
      The inclusion of two doses in the proposed pilot study is intended to determine a dose
      response effect and select a dose that is optimally safe and effective. The primary endpoint
      evaluation of time to fit for discharge will provide an effective objective measurement for
      the treatment effectiveness compared to standard supportive treatment of bronchiolitis.

      NO therapy can be cost effective, technologically simple and easily adaptive for use in
      inhaled pulmonary infections. Ultimately, therapeutic use of NO could be the initial
      treatment by mimicking the body's natural first line method to fight infections. Together,
      these results and rationale warrant the need to accelerate research of NO as a potential
      solution for front line treatment for bronchiolitis.

      Primary objective:

      • Assess whether Nitric Oxide (NO) administered intermittently in 2 concentrations (via
      inhalation for 40 minutes 4 times per day for up to 5 consecutive days) in addition to
      Standard Supportive Treatment (SST) shortens the recovery time of infants with bronchiolitis,
      compared to SST alone.

      Secondary objectives:

        -  Time to achieve O2 saturation of ≥ 92 % sustained for at least 2 hours

        -  Reduction in hospital Length of Stay (LOS)

        -  Time to achieve mTal score of ≤ 5

      Safety objectives: Characterize the safety of 2 doses of NO intermittent inhalation treatment
      therapy as measured by Adverse Events (AE) - number and percentage of subjects that
      experience AEs - and Serious Adverse Events (SAEs).

      A total of 90 subjects will be enrolled into the study and randomized in a 1:1:1 ratio to
      receive the study treatments.

      Treatment administration: Treatment blindness will be kept by designation of blinded and
      un-blinded team members.The blinded staff will be performing the study assessment procedures
      and the un-blinded team will be administering the actual treatment.

      Subjects' parents/legal guardian will be contacted for a follow up phone call at days 14+5
      and 30+5 from the date of enrollment of the subject into the study.
    

Intervention name(s): Nitric Oxide; Standard Supportive treatment
Intervention type(s): Drug; Other
Intervention description(s): Nitric Oxide given intermittently via inhalation; Standard Supportive treatment (including oxygen)
Intervention MeSH terms: Nitric Oxide
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment