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

NCT04060979 | Completed Phase 2

• 1 other identifier: AIT_CP_BRONC_03.01
• Study Type: interventional
• Target: 95
• Locations: 1 country
• Sites: 7

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.

Conditions

Bronchiolitis Acute

Outcome Measures

Primary Outcomes (1)

• Time to "fit for discharge"

  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).

  up to 14 days

Secondary Outcomes (4)

• Time to achieve O2 saturation of ≥ 92 %. sustained for at least 2 hours

  up to 14 days

• Hospital Length of Stay (LOS)

  up to 14 days

• Modified Tal score [mTal] ≤5

  up to 14 days

• Incidence of Treatment-Emergent Adverse Events

  Baseline to 30 days post dose

Other Outcomes (5)

• Admissions to ICU

  from enrollment till end of follow up period (30+5 days from enrollment)

• Duration of O2 supplementation (in hours)

  up to 14 days

• Level of O2 supplementation (in %)

  up to 14 days

Study Arms (3)

Group 1- NO treatment- dose 1

EXPERIMENTAL

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; Other: Standard Supportive treatment

Group 2- NO treatment- dose 2

EXPERIMENTAL

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; Other: Standard Supportive treatment

Group 3- Control treatment

OTHER

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

Interventions

Nitric Oxide DRUG

Nitric Oxide given intermittently via inhalation

Group 1- NO treatment- dose 1; Group 2- NO treatment- dose 2

Standard Supportive treatment OTHER

Standard Supportive treatment (including oxygen)

Group 1- NO treatment- dose 1; Group 2- NO treatment- dose 2; Group 3- Control treatment

Eligibility Criteria

• Age: 1 Day - 12 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Pediatric subjects up to 12-months of age, including subjects born ≥ 28 weeks of gestation.
• Subjects with acute bronchiolitis requiring in-patient hospitalization expected to last 24 hours or more.
• 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.
• Screening SpO2 of 92% or less in room-air
• A parent/guardian who is willing to comply with the study procedures and signs an informed consent on behalf of the subject.

You may not qualify if:

• Subjects diagnosed with alveolar pneumonia by chest X-ray and white blood cell (WBC)≥ 15,000/ul and Temp \>39°C
• Previous diagnosis of asthma or cough lasting more than 4 weeks or chronic requirement for asthma medications.
• Subjects with 2 or more previous physician diagnosed wheezing episodes.
• Any previous intensive care unit admission for respiratory distress or respiratory-related illness
• Diagnosis of Bronchopulmonary Dysplasia (BPD) based on medical history and home oxygen use.
• Subjects on home oxygen use for any reason
• Presence or use of a nasogastric or orogastric feeding tube
• Subjects with history of methemoglobinemia, known hereditary methemoglobinemia, and/or methemoglobin \>2% for any cause.
• 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.
• History of frequent epistaxis (\>1 episode/month) or significant hemoptysis within 30 days prior to enrollment (≥5 mL of blood in one coughing episode)
• Taken medications such as chronic systemic corticosteroids, central nervous system (CNS) stimulants, theophylline or aminophylline, anti-arrhythmic within 30 days of screening.
• Diagnosed with an underlying condition, which significantly affects respiratory system:
• Cystic fibrosis (CF), primary ciliary dyskinesia, non-CF bronchiectasis
• Immune deficiency
• Genetic or neurological disorder capable of causing:

Sponsors & Collaborators

• Beyond Air Inc.: lead

Study Sites (7)

Haemek Medical Center

Afula, Israel

Location

Assuta Ashdod

Ashdod, Israel

Location

Soroka Medical Center

Beersheba, Israel

Location

Carmel MEdical Center

Haifa, Israel

Location

Shaarei Zedek Medical Center

Jerusalem, Israel

Location

Schneider Children's hospital

Petah Tikva, Israel

Location

Sheba Medical Center

Tel Litwinsky, Israel

Location

Related Publications (1)

• Goldbart A, Lavie M, Lubetzky R, Pillar G, Landau D, Schlesinger Y, Spiegel R, Golan-Tripto I, Nahum A, Greenberg D, Tal A. Inhaled Nitric Oxide for the Treatment of Acute Bronchiolitis: A Multicenter Randomized Controlled Clinical Trial to Evaluate Dose Response. Ann Am Thorac Soc. 2023 Feb;20(2):236-244. doi: 10.1513/AnnalsATS.202103-348OC.

  PMID: 36169967 DERIVED

MeSH Terms

Interventions

Nitric Oxide

Intervention Hierarchy (Ancestors)

Reactive Nitrogen Species; Free Radicals; Inorganic Chemicals; Nitrogen Oxides; Nitrogen Compounds; Oxides; Oxygen Compounds; Organic Chemicals

Study Officials

• Aviv Goldbart

  Soroka University Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 11, 2019
• First Posted: August 19, 2019
• Study Start: November 6, 2019
• Primary Completion: March 2, 2020
• Study Completion: April 2, 2020
• Last Updated: May 12, 2020

Record last verified: 2020-01

Data Sharing

• IPD Sharing: Will not share

Locations

IL (7)