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Evaluation of Two Doses of Nitric Oxide (NO) Given Intermittently Via Inhalation to Subjects With Bronchiolitis

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ClinicalTrials.gov Identifier: NCT04060979
Recruitment Status : Recruiting
First Posted : August 19, 2019
Last Update Posted : January 28, 2020
Sponsor:
Information provided by (Responsible Party):
Beyond Air Ltd

Brief 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.


Condition or disease Intervention/treatment Phase
Bronchiolitis Acute Drug: Nitric Oxide Other: Standard Supportive treatment Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 90 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Prospective, Double-Blinded, Randomized, Multi-Center Study for Evaluation of Two Doses of Nitric Oxide (NO) Given Intermittently Via Inhalation to Subjects With Bronchiolitis
Actual Study Start Date : November 6, 2019
Estimated Primary Completion Date : February 2020
Estimated Study Completion Date : April 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Group 1- NO treatment- dose 1
Will comprise of approximately 30 patients and will receive inhalations of dose 1 of NO combined with O2/air for 40 minutes, every 4.5 hours during the day four times a day for up to 5 days in addition to standard supportive treatment.
Drug: Nitric Oxide
Nitric Oxide given intermittently via inhalation

Other: Standard Supportive treatment
Standard Supportive treatment (including oxygen)

Experimental: Group 2- NO treatment- dose 2
Will comprise of approximately 30 patients and will receive inhalations of dose 2 of NO combined with O2/air for 40 minutes, every 4.5 hours during the day four times a day for up to 5 days in addition to standard supportive treatment.
Drug: Nitric Oxide
Nitric Oxide given intermittently via inhalation

Other: Standard Supportive treatment
Standard Supportive treatment (including oxygen)

Group 3- Control treatment
Will comprise of approximately 30 patients and will receive O2/air using the same treatment schedule and equipment as groups 1 and 2, in addition to standard supportive treatment.
Other: Standard Supportive treatment
Standard Supportive treatment (including oxygen)




Primary Outcome Measures :
  1. Time to "fit for discharge" [ Time Frame: up to 14 days ]

    Time to "fit for discharge". "Fit for discharge" is a composite endpoint measured by the following:

    • Achieving Modified Tal score [mTal] ≤ 5 And
    • Oxygen saturation (SpO2) ≥92% at room air (without oxygen supplementation) sustained for at least 2 hours Both of these will be determined from the time of enrollment (when the ICF is signed).


Secondary Outcome Measures :
  1. Time to achieve O2 saturation of ≥ 92 %. sustained for at least 2 hours [ Time Frame: up to 14 days ]
    The time in hours calculated from the time of patient's enrollment until the time required to achieve the endpoint.

  2. Hospital Length of Stay (LOS) [ Time Frame: up to 14 days ]
    LOS is measured in hours from the time of patient's enrollment in the study until the physician's order to discharge from the hospital. A patient will be evaluated for discharge from the hospital only after meeting the primary efficacy endpoint.

  3. Modified Tal score [mTal] ≤5 [ Time Frame: up to 14 days ]
    The time in hours calculated from the time of patient's enrollment until the time required to achieve a clinical score of less than or equal to 5.

  4. Incidence of Treatment-Emergent Adverse Events [ Time Frame: Baseline to 30 days post dose ]
    Number of treatment-emergent adverse events (AEs) and Serious AEs


Other Outcome Measures:
  1. Admissions to ICU [ Time Frame: from enrollment till end of follow up period (30+5 days from enrollment) ]
    Number of admissions to ICU

  2. Duration of O2 supplementation (in hours) [ Time Frame: up to 14 days ]
    Duration of O2 supplementation (in hours)

  3. Level of O2 supplementation (in %) [ Time Frame: up to 14 days ]
    Level of O2 supplementation (in %)

  4. Nasopharyngeal swab testing for detecting respiratory viruses at baseline and end of treatment [ Time Frame: up to 14 days ]
    Nasopharyngeal swab testing for detecting respiratory viruses at baseline and end of treatment. Will be performed for exploratory purposes only.

  5. Readmission related to bronchiolitis [ Time Frame: 30 days from enrollment ]
    Readmission related to bronchiolitis - percentage of readmissions, related to bronchiolitis within 30 days from enrollment



Information from the National Library of Medicine

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, Learn About Clinical Studies.


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

Inclusion Criteria:

  1. Pediatric subjects up to 12-months of age, including subjects born ≥ 28 weeks of gestation.
  2. Subjects with acute bronchiolitis requiring in-patient hospitalization expected to last 24 hours or more.
  3. Modified Tal Score (mTal) between 7 to 10 at screening. Note that the oxygen requirement section of the clinical score reflects patient's oxygen saturation without oxygen supplementation.
  4. Screening SpO2 of 92% or less in room-air
  5. A parent/guardian who is willing to comply with the study procedures and signs an informed consent on behalf of the subject.

Exclusion Criteria:

  1. Subjects diagnosed with alveolar pneumonia by chest X-ray and white blood cell (WBC)≥ 15,000/ul and Temp >39°C
  2. Previous diagnosis of asthma or cough lasting more than 4 weeks or chronic requirement for asthma medications.
  3. Subjects with 2 or more previous physician diagnosed wheezing episodes.
  4. Any previous intensive care unit admission for respiratory distress or respiratory-related illness
  5. Diagnosis of Bronchopulmonary Dysplasia (BPD) based on medical history and home oxygen use.
  6. Subjects on home oxygen use for any reason
  7. Presence or use of a nasogastric or orogastric feeding tube
  8. Subjects with history of methemoglobinemia, known hereditary methemoglobinemia, and/or methemoglobin >2% for any cause.
  9. Use of an investigational drug or device within 30 days before enrollment and/or expected to participate in a new study within 90 days of enrollment.
  10. History of frequent epistaxis (>1 episode/month) or significant hemoptysis within 30 days prior to enrollment (≥5 mL of blood in one coughing episode)
  11. Taken medications such as chronic systemic corticosteroids, central nervous system (CNS) stimulants, theophylline or aminophylline, anti-arrhythmic within 30 days of screening.
  12. Diagnosed with an underlying condition, which significantly affects respiratory system:

    1. Cystic fibrosis (CF), primary ciliary dyskinesia, non-CF bronchiectasis
    2. Immune deficiency
    3. Genetic or neurological disorder capable of causing:

      • Impaired respiratory secretions clearance including insufficient cough
      • chronic respiratory failure and insufficiency
      • restrictive lung disease
    4. Conditions that decrease the muscle strength
    5. Glucose 6-phosphate dehydrogenase deficiency
    6. 6-Phosphogluconate dehydrogenase deficiency
    7. Trisomy 21 (Down Syndrome)
  13. Presence of upper airway anomalies that may interfere with breathing, including:

    1. Choanal atresia or stenosis
    2. Cleft lip and palate
    3. Tracheo-esophageal fistula
    4. Tracheal stenosis
    5. Tracheomalacia and/or bronchomalacia
  14. History of severe aspiration pneumonia
  15. Having the following signs or symptoms:

    1. clinically significant pulmonary (lung) and/or cardiac (heart) congenital malformations
    2. an underlying renal, or liver insufficiency, immunodeficiency, encephalopathy;
    3. known or suspected foreign body aspiration during enrollment.
  16. If the first treatment cannot start within 6 hours after signing of the informed consent form (ICF), the subject is not eligible for enrollment.
  17. Symptoms (i.e., cough and wheezing) started longer than 72 h before admission to the hospital
  18. Per Investigator's discretion, the subject parents/legal guardian(s) are unable to comply with the study procedures.
  19. Any reason that, in the opinion of the investigator, may make the subject unfit for this clinical trial.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04060979


Contacts
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Contact: Vladislava Zamfirova, MD 516-833-5490 vzamfirova@beyondair.net

Locations
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Israel
Haemek Medical Center Recruiting
Afula, Israel
Contact: Ronen Spiegel    +972-4-6495512    spiegel_ro@clalit.org.il   
Assuta Ashdod Recruiting
Ashdod, Israel
Contact: Yonatan Yeshayahu    +972-72-3398778    yeshayahu@assuta.co.il   
Soroka Medical Center Recruiting
Be'er Sheva, Israel
Contact: Aviv Goldbart    +972-54-3181700    avivgold@bgu.ac.il   
Carmel MEdical Center Recruiting
Haifa, Israel
Contact: Giora Pillar    +972-4-8250354    giorapi@clalit.org.il   
Shaarei Zedek Medical Center Recruiting
Jerusalem, Israel
Contact: Yechiel Schlezinger    +972-2-6555445    yechiel@szmc.org.il   
Schneider Children's hospital Recruiting
Pethah Tiqvā, Israel
Contact: Daniel Landau    +972-3-9253779    Danny_L@clalit.org.il   
Sheba Medical Center Recruiting
Tel HaShomer, Israel
Contact: Gilad Sherman    +972-3-5304430    Gilad.Sherman@sheba.health.gov.il   
Sponsors and Collaborators
Beyond Air Ltd
Investigators
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Principal Investigator: Aviv Goldbart Soroka University Medical Center

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Responsible Party: Beyond Air Ltd
ClinicalTrials.gov Identifier: NCT04060979    
Other Study ID Numbers: AIT_CP_BRONC_03.01
First Posted: August 19, 2019    Key Record Dates
Last Update Posted: January 28, 2020
Last Verified: January 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Bronchiolitis
Respiratory Tract Diseases
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
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