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Evaluation of the Efficacy Safety and Tolerability of Nitric Oxide Given Intermittently Via Inhalation to Subjects With Bronchiolitis

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2017 by Advanced Inhalation Therapies Ltd
Sponsor:
Information provided by (Responsible Party):
Advanced Inhalation Therapies Ltd
ClinicalTrials.gov Identifier:
NCT03053388
First received: February 12, 2017
Last updated: March 13, 2017
Last verified: February 2017
  Purpose

Double blind, randomized multi-center, evaluation of the efficacy, safety and tolerability of Nitric Oxide (NO) given intermittently via inhalation to subjects with acute bronchiolitis.

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.

Nitric Oxide (NO) has been shown to play a critical role in various biological functions, including in the vasodilatation of smooth muscle, neurotransmission, regulation of wound healing and during immune responses to infection with a microbicidal action directed toward various organisms. In the airways, NO is considered to play a key role in the innate immune system in which the first-line of host defense against microbes is built.

The beneficial effect of NO has been shown in different diseases with several options of doses and regimens; newborn with primary pulmonary hypertension showed improvement in oxygenation after 30 minutes of NO treatment at 10-20 ppm, while subjects with adult respiratory distress syndrome demonstrated clinical improvement during NO treatment at 18 and 36 ppm.

In vitro studies 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.

Safety and tolerability of 160 ppm NO given intermittently via inhalation were shown in a phase II study performed on 2-12 month infants hospitalized with bronchiolitis. According to data no difference in the proportion of adverse events and serious adverse events were detected between subjects treated with NO and subjects treated with standard supportive treatment.

In this study the investigators wish to assess the efficacy of 160 ppm NO given intermittently via inhalation to 0-12 months-old infants hospitalized due to acute bronchiolitis.

Primary objective: Asses the difference in hospital Length of Stay (LOS) between subjects treated with 160 ppm NO combined with standard supportive treatment and subjects treated with standard supportive treatment.

Secondary objectives: Asses the difference in the time required to achieve clinical improvement, a clinical score ≤5 (Modified Tal score) between subjects treated with 160 ppm NO combined with standard supportive treatment and subjects treated with standard supportive treatment. Assess the difference in the time required to achieve sustained 92% oxygen saturation in room air between subjects treated with 160 ppm NO combined with standard supportive treatment and subjects treated with standard supportive treatment. Characterize the safety and tolerability of 160 ppm NO intermittent inhalation treatment as measure by the rate of adverse events.

In this prospective double-blind, randomized multi-Center study the investigators will enroll up to 120 (no less than 80) subjects aged 0-12 months-old, diagnosed with acute bronchiolitis and requiring in-patient hospitalization.

Enrolled subjects will be randomized into 2 groups. Group 1 -Treatment group - Will receive 160 ppm NO given intermittent via inhalation in addition to standard treatment for up to 5 days. Group 2 - will receive ongoing inhalation of the standard treatment for up to 5 days. Between study and after completing all study inhalations the subject will continue to receive the standard treatment. Oxygen (O2), NO, nitrogen dioxide (NO2) and fraction of inspired oxygen (FiO2) delivered to the patient will be continuously monitored.

Treatment administration: Treatment blindness will be kept by separating between un-blinded team members (giving the actual treatment) and blinded team members, and by hiding the NO container and all study related equipment behind a curtain.

All subjects will return for follow-up visits on day 14(+5), 21(+5) days and will be contacted on day 30 (+5) from day of admission to the department.


Condition Intervention Phase
Bronchiolitis
Drug: Nitric Oxide
Other: Supportive treatment
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Participant, Care Provider, Investigator, Outcomes Assessor
Primary Purpose: Treatment
Official Title: Evaluation of the Efficacy 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:
  • Hospital Length of Stay (LOS) [ Time Frame: 30 days ]
    The difference in hospital Length of Stay (LOS) in hours between subjects treated with 160 ppm Nitric Oxide combined with standard supportive treatment and subjects treated with standard supportive treatment.


Secondary Outcome Measures:
  • Time to achieve a clinical score of ≤5 (Modified Tal score) [ Time Frame: 30 days ]
    The difference in the time required to achieve a clinical score of ≤5 (Modified Tal score) between subjects treated with 160 ppm NO combined with standard supportive treatment and subjects treated with standard supportive treatment

  • Time to achieve ≥92% oxygen saturation (SaO2) [ Time Frame: 30 days ]
    The difference in the time to achieve ≥92% oxygen saturation in hours between subjects treated with 160 ppm Nitric Oxide combined with standard supportive treatment and subjects treated with standard supportive treatment.

  • Measure the rate of NO-related adverse events as well as methaemoglobinaemia and nitrogen dioxide levels [ Time Frame: 5 days ]

Estimated Enrollment: 120
Actual Study Start Date: March 5, 2017
Estimated Study Completion Date: August 19, 2017
Estimated Primary Completion Date: August 19, 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Group 1 - Nitric Oxide treatment
will receive standard supportive treatment (including O2) combined with the inhalation of 160ppm NO for 30 min every 4 hours (a minimum of 3 hours between the end of one treatment and the beginning of the next treatment), five times a day (24 hours) for up to 5 days (maximum 25 inhalations).
Drug: Nitric Oxide
Nitric Oxide given via inhalation in cycles
Other: Supportive treatment
Supportive treatment (including oxygen)
Placebo Comparator: Group 2 - Control treatment
will receive standard supportive treatment (including O2) for 30 min every 4 hours (a minimum of 3 hours between the end of one treatment and the beginning of the next treatment), five times a day (24 hours) for up to 5 days (maximum 25 inhalations).
Other: Supportive treatment
Supportive treatment (including oxygen)

  Eligibility

Ages Eligible for Study:   up to 12 Months   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Pediatric subjects 0-12-months old
  2. Subjects that were born at ≥28 weeks of gestation
  3. Subjects with acute bronchiolitis requiring in-patient hospitalization expected for 24 hours and more
  4. Room-air SaO2 ≤ 89% prior to initiation of standard O2 therapy
  5. Clinical score of ≥8 at Screening (without oxygen supplementation)
  6. Parent/guardian who is willing and able to sign, an informed consent on behalf of the subject.

Exclusion Criteria:

  1. Subjects diagnosed with alveolar pneumonia on Chest X-ray (including WBC≥ 15,000ul, and Temp >39C)
  2. Previous diagnosis of asthma or requirement for asthma medications
  3. Infants with >2 previous wheezing episodes
  4. History of life-threatening respiratory distress that requires admission to an intensive care unit for treatment
  5. Subjects with history of methaemoglobinaemia and/or methaemoglobin >5% for any cause
  6. Use of an investigational drug within 30 days before enrolment and not expected to participate in a new study within 90 days
  7. History of frequent epistaxis (>1 episode/month) or significant hemoptysis within 30 days (≥ 5 mL of blood in one coughing episode or >30 mL of blood in a 24-hour period)
  8. Taken medications such as chronic systemic corticosteroids, CNS stimulants, theophylline or aminophylline, anti-arrhythmic within a certain time period prior to the study.
  9. Unable to comply with the study procedures.
  10. Underlying genetic disorders (including Cystic fibrosis) or hypotonia
  11. Having the following signs or symptoms: 1) present with known pulmonary (lung) and/or cardiac (heart) congenital malformations 2) have an underlying renal, or liver insufficiency, immunodeficiency, encephalopathy); 3) known or suspected foreign body aspiration;
  12. Diagnosed with influenza at the time of enrollment by a kit
  13. Any reason that, in the opinion of the investigator, may make the subject unfit for this clinical trial
  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: NCT03053388

Contacts
Contact: Aviv Goldbart, Dr +972-543181700 avivgold@bgu.ac.il

Locations
Israel
Soroka Medical Center Recruiting
Beer Sheva, Israel
Sponsors and Collaborators
Advanced Inhalation Therapies Ltd
  More Information

Responsible Party: Advanced Inhalation Therapies Ltd
ClinicalTrials.gov Identifier: NCT03053388     History of Changes
Other Study ID Numbers: AIT_CP_BRONC02.01
Study First Received: February 12, 2017
Last Updated: March 13, 2017
Individual Participant Data  
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Bronchiolitis
Bronchitis
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Tract Infections
Nitric Oxide
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Asthmatic Agents
Respiratory System Agents
Free Radical Scavengers
Antioxidants
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Endothelium-Dependent Relaxing Factors
Vasodilator Agents
Gasotransmitters
Protective Agents

ClinicalTrials.gov processed this record on March 28, 2017