Evaluation of the Safety and Tolerability of Nitric Oxide (NO) Via Inhalation to Subjects With Bronchiolitis

Phase IIa Prospective, Double Blind, Randomized Single-Center, Evaluation of the Safety and Tolerability of Nitric Oxide Given Intermittently Via Inhalation to Subjects With Bronchiolitis

Prospective, Double Blind, Randomized Single-Center, Evaluation of Safety and Tolerability of Nitric Oxide Given Intermittently via Inhalation to Subjects with Bronchiolitis-Phase IIa Bronchiolitis is defined as an infection of the small airways. It is also the most common manifestation of acute lower respiratory infection (ALRI) in early infancy, and is the leading cause of global child mortality. NO has been shown to play a critical role in various biological functions, including the vasodilatation of smooth muscle, neurotransmission, regulation of wound healing and immune responses to infection such as microbicidal action directed toward various organisms. NO in the airways is considered to play a key role in the innate immune system in which the first-line of host defense against microbes is built.

It has shown the beneficial effect of NO in different diseases with several options of doses and regimens - from newborn with primary pulmonary hypertension which showed improvement in oxygenation after 30 minutes of NO treatment at 10-20 ppm, to a subject with adult respiratory distress syndrome, who demonstrated clinical improvement during NO treatment at 18 and 36 ppm.

In vitro studies utilizing a variety of nitric oxide (NO) donors suggested that NO, in part per million (ppm) concentrations, possesses antimicrobial and anti-viral activity against a wide variety of phyla including bacteria, viruses, helminthes and parasites.

Primary Objectives: Assess the safety of NO intermittent inhalation treatment in 2-12 month old bronchiolitis subjects. Assess the tolerability of NO intermittent inhalation treatment in 2-12 month old bronchiolitis subjects Secondary Objective: Assess the efficacy of NO intermittent inhalation treatment compared to standard treatment in 2-12 months old bronchiolitis subjects.

Prospective, double blind, randomized single-Center study of 44 hospitalized subjects aged 2 -12 months old, diagnosed with bronchiolitis will be enrolled into the study and randomized into 2 groups. Group 1 -Treatment group - Will receive nitric oxide inhalation in addition to standard treatment for up to 5 days, Group 2 - will receive ongoing inhalation of the standard treatment for 5 days.

Treatment administration: Treatment blindness will be kept by separating between unblinded team members (giving the actual treatment) and blinded team members, and by hiding the NO container and all study related equipment behind a curtain. Between study inhalations the subject will continue to receive the standard inhalation treatment. Oxygen (O2), NO , nitrogen dioxide(NO2)and fraction of inspired oxygen (FiO2) delivered to the patient will be continuously monitored.

All subjects will come for follow up visits on day 7(+5), 14 (+5) days and will be contacted on day 30 (+5) from day of admission to the department.

End of study treatment (both groups) will be assessed by a blinded study physician base on clinical assessment. Subject improvement that will lead to end study treatment = clinical score < 6 and/or (Oxygen saturation)SaO2 above 92% and/or decision of subject discharge from the hospital.

Study Overview

• Status: Completed
• Conditions: Bronchiolitis
• Intervention / Treatment: Drug: Placebo; Drug: Nitric Oxide

• Study Type: Interventional
• Enrollment (Actual): 43
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Israel
  • Beer-Sheba, Israel, 84101
    • Soroka university

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 months to 1 year (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subjects (Male or female) 2-12 months old
• Diagnosed as bronchiolitis
• Parents/ legal guardian signed informed consent.

Exclusion Criteria:

• Subjects diagnosed with concomitant diseases such as pneumonia,urine tract infection (UTI) or otitis media
• Prematurity <36 weeks gestational age.
• Received (Respiratory syncytial virus) RSV immunoglobulin prophylaxis
• Subjects diagnosed with, methemoglobinemia, chronic lung disease, immune deficiency, heart disease
• Use of an investigational drug within 30 days before enrollment and not expected to participate in a new study within 30 days
• History of frequent epistaxis (>1 episode/month)
• Significant hemoptysis within 30 days (≥ 5 mL of blood in one coughing episode or > 30 mL of blood in a 24 hour period)
• Methemoglobin >3% at screening
• Subjects cannot fulfill the study design
• Presence of a condition or abnormality that in the opinion of the Investigator would compromise the safety of the subject or the quality of the data.
• Underlying diseases such as genetic disorders (Cystic fibrosis, Down Syndrome) or chronic lung diseases (Bronchopulmonary dysplasia,Primary ciliary dyskinesia, Bronchiolitis Obliterans), hypotonia, Congenital heart disease)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Nitric oxide inhalation + standard treatment; Inhalation of 160 ppm gNO for 30 minutes, 5 times daily, for 5 consecutive days or until discharged, which occurs first.	Drug: Nitric Oxide
Placebo Comparator: Standard treatment	Drug: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Met-Hemoglobin percentage (MetHb) associated with inhaled NO	21 days
Number of participants with adverse events associated with inhaled NO as a measure of safety and tolerability	5 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Proportion of subjects (%) who prematurely discontinued the study due to adverse events (AEs)	5 days

Other Outcome Measures

Outcome Measure	Time Frame
Comparing the Length of hospital stay (LOS) in days of subjects 2-12 months old with bronchiolitis treated with NO and standard treatment versus subjects treated with standard treatment	5 days

Collaborators and Investigators

• Sponsor: Beyond Air Inc.
• Collaborators: Soroka University Medical Center
• Investigators: Principal Investigator: Asher Tal, M.D, Soroka University Medical Center

Study record dates

Study Major Dates

• Study Start: January 1, 2013
• Primary Completion (Actual): January 1, 2016
• Study Completion (Actual): January 1, 2016

Study Registration Dates

• First Submitted: January 14, 2013
• First Submitted That Met QC Criteria: January 15, 2013
• First Posted (Estimate): January 16, 2013

Study Record Updates

• Last Update Posted (Estimate): May 4, 2016
• Last Update Submitted That Met QC Criteria: May 3, 2016
• Last Verified: May 1, 2016

More Information

Terms related to this study

• Keywords: inhalation; Infants; NO; Bronchiolitis
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Respiration Disorders; Lung Diseases; Bronchial Diseases; Lung Diseases, Obstructive; Bronchitis; Respiratory Aspiration; Bronchiolitis; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Autonomic Agents; Peripheral Nervous System Agents; Protective Agents; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Antioxidants; Free Radical Scavengers; Endothelium-Dependent Relaxing Factors; Gasotransmitters; Nitric Oxide
• Other Study ID Numbers: AIT_CP_BRONC01.01