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

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2013 by Advanced Inhalation Therapies Ltd
Sponsor:
Collaborator:
Soroka University Medical Center
Information provided by (Responsible Party):
Advanced Inhalation Therapies Ltd
ClinicalTrials.gov Identifier:
NCT01768884
First received: January 14, 2013
Last updated: December 12, 2013
Last verified: December 2013
  Purpose

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.


Condition Intervention Phase
Bronchiolitis
Drug: Nitric Oxide
Drug: Placebo
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Advanced Inhalation Therapies Ltd:

Primary Outcome Measures:
  • Met-Hemoglobin percentage (MetHb) associated with inhaled NO [ Time Frame: 21 days ] [ Designated as safety issue: Yes ]
  • Number of participants with adverse events associated with inhaled NO as a measure of safety and tolerability [ Time Frame: 5 days ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Proportion of subjects (%) who prematurely discontinued the study due to adverse events (AEs) [ Time Frame: 5 days ] [ Designated as safety issue: Yes ]

Other Outcome Measures:
  • 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 [ Time Frame: 5 days ] [ Designated as safety issue: No ]

Estimated Enrollment: 44
Study Start Date: January 2013
Estimated Study Completion Date: August 2014
Estimated Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
Standard treatment
Drug: Placebo

  Eligibility

Ages Eligible for Study:   2 Months to 1 Year
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01768884

Contacts
Contact: David Greenberg, M.D 972-8-6400547 Dudi@bgu.ac.il
Contact: Racheli Vizman, Bsc. 972-775071072 racheli@ait-pharm.con

Locations
Israel
Soroka university Recruiting
Beer-Sheba, Israel, 84101
Contact: Asher Tal, M.D    972-8-6403400    Asik@bgu.ac.il   
Contact: Aviv Goldbart, M.D    972-8-6400656    avivgold@bgu.ac.il   
Principal Investigator: Asher Tal, M.D         
Sponsors and Collaborators
Advanced Inhalation Therapies Ltd
Soroka University Medical Center
Investigators
Principal Investigator: Asher Tal, M.D Soroka University Medical Center
  More Information

No publications provided

Responsible Party: Advanced Inhalation Therapies Ltd
ClinicalTrials.gov Identifier: NCT01768884     History of Changes
Other Study ID Numbers: AIT_CP_BRONC01.01
Study First Received: January 14, 2013
Last Updated: December 12, 2013
Health Authority: Israel: Ministry of Health

Keywords provided by Advanced Inhalation Therapies Ltd:
Infants
Bronchiolitis
NO
inhalation

Additional relevant MeSH terms:
Bronchiolitis
Respiratory Aspiration
Respiration Disorders
Respiratory Tract Diseases
Signs and Symptoms, Respiratory
Signs and Symptoms
Bronchitis
Bronchial Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Tract Infections
Nitric Oxide
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Asthmatic Agents
Respiratory System Agents
Therapeutic Uses
Free Radical Scavengers
Antioxidants
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Endothelium-Dependent Relaxing Factors
Vasodilator Agents
Cardiovascular Agents
Protective Agents

ClinicalTrials.gov processed this record on July 22, 2014